bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isoflurane, but Not Sevoflurane, Increases Transendothelial Albumin Permeability in the Isolated Rat Lung
Authors: Hu Guochang , Schwartz David E. , Shajahan Ayesha N. , Visintine David J. , Salem M Ramez , Crystal George J. , Albrecht Ronald F. , Vogel Stephen M. , Minshall Richard D. 
Published: March 2006

Background
Caveolae mediated transendothelial transport of albumin has recently been shown to be the primary mechanism regulating microvascular endothelial albumin permeability. The authors investigated the effects of isoflurane and sevoflurane on pulmonary endothelial albumin permeability and assessed the potential role of the caveolae scaffold protein, caveolin-1, in these effects.

Methods
Isolated rat lungs and cultured rat lung microvessel endothelial cells (RLMVECs) were exposed to 1.0 or 2.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 30 min. I-albumin permeability-surface area product and capillary filtration coefficient were determined in the isolated lungs. In RLMVECs, uptake and transendothelial transport of I-albumin were measured in the absence and presence of pretreatment with 2 mm methyl-beta-cyclodextrin, a caveolae-disrupting agent. Uptake of fluorescent-labeled albumin, as well as phosphorylation of Src kinase and caveolin-1, was also determined. In Y14F-caveolin-1 mutant (nonphosphorylatable) expressing RLMVECs, uptake of I-albumin and phosphorylation of caveolin-1 were evaluated.

Results
In the isolated lungs, 2.0 MAC isoflurane increased I-albumin permeability-surface area product by 48% without affecting capillary filtration coefficient. In RLMVECs, isoflurane more than doubled the uptake of I-albumin and caused a 54% increase in the transendothelial transport of I-albumin. These effects were blocked by pretreatment with methyl-beta-cyclodextrin. The isoflurane-induced increase in uptake of I-albumin in wild-type RLMVECs was abolished in the Y14F-caveolin-1 mutant expressing cells. Isoflurane also caused a twofold increase in Src and caveolin-1 phosphorylation. Neither 1.0 MAC isoflurane nor 1.0 or 2.0 MAC sevoflurane affected any index of albumin transport or phosphorylation of caveolin-1.

Conclusion
Isoflurane, but not sevoflurane, increased lung transendothelial albumin permeability through enhancement of caveolae-mediated albumin uptake and transport in the isolated lung. This effect may involve an enhanced phosphorylation of caveolin-1.
Intravenous Anesthetics Inhibit Capacitative Calcium Entry in Pulmonary Venous Smooth Muscle Cells
Authors: Shimizu Sachiko , Ding Xueqin , Murray Paul A. 
Published: March 2006

Background
The authors have previously demonstrated that propofol attenuates capacitative calcium entry (CCE) via the protein kinase C signaling pathway in pulmonary artery smooth muscle cells (PVSMCs). The current goals were to determine whether CCE exists in PVSMCs; to assess the roles of the protein kinase C, tyrosine kinase (TK), and rho-kinase signaling pathways in regulating CCE; and to investigate the extent and cellular mechanisms by which intravenous anesthetics (thiopental, midazolam, ketamine, and propofol) alter CCE.

Methods
Primary cultures of fura-2-loaded canine PVSMCs were placed in a dish (37 degrees C) on an inverted fluorescence microscope. Intracellular Ca2+ concentration ([Ca2+]i) was measured as the 340/380 fluorescence ratio in individual PVSMCs. Thapsigargin, a sarcoplasmic reticulum Ca2+-adenosine triphosphatase inhibitor, was used to deplete intracellular Ca2+ stores after removing extracellular Ca2+. CCE was then activated by restoring extracellular Ca2+ (2.2 mm).

Results
Thapsigargin caused a transient increase in [Ca2+]i (160 +/- 6%). Restoring extracellular Ca2+ caused a rapid peak increase in [Ca2+]i (155 +/- 7% of baseline), followed by a sustained increase in [Ca2+]i (129 +/- 5% of baseline), i.e., CCE was stimulated in PVSMCs. Neither protein kinase C activation nor inhibition had an effect on CCE. rho-Kinase inhibition also had no effect on CCE, whereas TK inhibition attenuated both peak and sustained CCE. Thiopental, midazolam, ketamine, and propofol each attenuated both peak and sustained CCE. TK inhibition abolished the thiopental-, midazolam-, and ketamine-induced, but not the propofol-induced, decreases in CCE.

Conclusion
Capacitative calcium entry is present in canine PVSMCs. Thiopental, midazolam, and ketamine attenuate CCE primarily via the TK signaling pathway. Propofol attenuates CCE via a TK-independent mechanism.
Bupivacaine Inhibits Activation of Neuronal Spinal Extracellular Receptor–activated Kinase through Selective Effects on Ionotropic Receptors
Authors: Yanagidate Fumi , Strichartz Gary R. 
Published: March 2006

Background
Central terminals of primary nociceptors release neurotransmitters glutamate and substance P, which bind to ionotropic or metabotropic receptors on spinal neurons to induce cellular responses. Extracellular signal-regulated kinases are activated by these receptors and are important modulators of pain at the dorsal horn. The authors investigated these pathways as potential targets for antinociceptive actions of local anesthetics.

Methods
The effects of bupivacaine on the activation of extracellular receptor-activated kinase (phosphorylation to pERK) in rat spinal cord slices, induced by presynaptic release (capsaicin), by presynaptic or postsynaptic ionotropic or metabotropic receptor activation, or by activation of intracellular protein kinase C or protein kinase A and also by a receptor-independent Ca2+ ionophore, were quantitated by immunohistochemistry, counting pERK-positive neurons in the superficial dorsal horn.

Results
Capsaicin (3 microm, 10 min)-stimulated pERK was reduced by bupivacaine (IC50 approximately 2 mm, approximately 0.05%), which similarly suppressed pERK induced by the ionotropic glutamate receptors for N-methyl-D-aspartate and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid but not that induced by the metabotropic receptors for glutamate, bradykinin, or substance P. Extracellular receptor-activated kinase activation by the Ca2+ ionophore ionomycin was also sensitive to bupivacaine, but direct activation by protein kinase A or protein kinase C was not.

Conclusions
Bupivacaine inhibits pERK activation resulting from different modes of Ca2+ influx through the plasma membrane. This represents a postsynaptic mechanism of analgesia that occurs in parallel with impulse inhibition during neuraxial blockade.
Subpopulation of Dorsal Horn Neurons Displays Enhanced N -methyl-d-aspartate Receptor Function after Chronic Morphine Exposure
Authors: Zhao Min , Joo Daisy Therese 
Published: March 2006

Background
Morphine tolerance may be attributed to enhancement of glutamatergic neurotransmission, in particular to increased function of the N-methyl-D-aspartate (NMDA) receptor. The cellular mechanisms responsible for these changes remain poorly defined. The authors identified and characterized a specific subpopulation of dorsal horn neurons, displaying NMDA receptor plasticity in response to chronic morphine administration.

Methods
The authors undertook current clamped and voltage clamped recordings of NMDA receptor-mediated responses from cultured rat dorsal horn neurons that were untreated or treated for 7 days with 1 or 100 microm morphine.

Results
Smaller (capacitance < or = 22 pF), tonic firing neurons showed a significantly enhanced NMDA receptor-mediated peak current after prolonged morphine treatment, whereas larger and phasic firing neurons showed no enhancement. With high-concentration but not low-concentration morphine treatment, Mg2+ blockade of NMDA receptors at resting membrane potentials was reduced. Furthermore, the chronic opioid-induced increase in NMDA current was attenuated by pretreatment with either a mu-opioid receptor inhibitor (naloxone) or an NMDA receptor inhibitor (2-amino-5-phosphonovalerate) (low-concentration > high-concentration morphine).

Conclusions
In an electrophysiologically defined subpopulation of dorsal horn neurons, enhanced NMDA receptor function after chronic morphine exposure was shown to be mechanistically dependent on morphine concentration and sensitive to both NMDA and mu-opioid receptor antagonism. Therefore, these changes observed in this population of sensory spinal neurons can be used to study the development and prevention of opioid tolerance described in multiple laboratory and clinical reports.
Predicting Patient Nonappearance for Surgery as a Scheduling Strategy to Optimize Operating Room Utilization in a Veterans' Administration Hospital
Authors: Basson Marc D. , Butler Timothy W. , Verma Harish 
Published: March 2006

Background
Previous attempts at improving operating room utilization have generally emphasized more accurate scheduling, starting the first case on time, and reducing turnover time. Surgical case cancellations have largely been ignored except for recommendations for preoperative screening and good physician-patient communication to improve patient compliance.

Methods
A retrospective review of operating room records was initially used to identify reasons for surgical cancellations. This was followed by a retrospective stratified case-control study of patient records to identify preexisting factors that predict the failure of patients to appear for surgical procedures as scheduled. Factors assessed included demographics, type of surgical procedure, compliance with previous healthcare visits, substance abuse, mental illness, travel distance, and neurologic problems.

Results
The authors reviewed their operating room utilization and found patient nonappearance rates to be a substantial source of surgical cancellations. Furthermore, multivariate analysis demonstrated that patient nonappearance could be strongly predicted from patient noncompliance with clinic visits and other clinical procedures without reference to the other variables assessed. Further analysis of data from an independent sample of patients confirmed this observation.

Conclusions
Noncompliance with hospital visits for surgical procedures can be predicted from noncompliance with other healthcare encounters. Surgical procedures for previously noncompliant patients should be booked at the end of the operating room day, when the cancellation is least likely to interfere with operating room flow.
Accelerated growth of intestinal tumours after radiation exposure in Mlh1‐knockout mice: evaluation of the late effect of radiation on a mouse model of HNPCC
Authors: Tokairin Yutaka , Kakinuma Shizuko , Arai Masami , Nishimura Mayumi , Okamoto Mieko , Ito Eisaku , Akashi Makoto , Miki Yoshio , Kawano Tatsuyuki , Iwai Takehisa , Shimada Yoshiya 
Published: March 2006

Summary Mlh1‐knockout mice have been developed as a useful model of hereditary non‐polyposis colorectal cancer (HNPCC). In this study, we analyzed the pathology of gastrointestinal tumours (GIT) in these mice in detail and examined the possible effects of ionizing radiation on the induction of intestinal tumours to evaluate the late response to radiotherapy in HNPCC. Mlh1–/– mice spontaneously developed GIT and thymic lymphomas by 48 weeks. GIT included not only well differentiated adenocarcinomas but also poorly differentiated and mucinous adenocarcinomas, suggesting that this mouse is a good model for HNPCC. In contrast to colon cancers from HNPCC patients, however, carcinomas of Mlh1–/– mice expressed p53 and showed a lack of transforming growth factor (TGF)‐βRII mutation, which resulted in the expression of TGF‐βRII protein. Irradiation of 10‐week‐old Mlh1–/– mice accelerated GIT development but had little effect at 2 weeks. Mlh1+/– and Mlh1+/+ mice were not susceptible to spontaneous or radiation‐induced thymic lymphomas and GIT until 72 weeks after birth. The development and pathology of GIT in Mlh1–/– mice suggest that this mouse is a good model for HNPCC, although tumour‐related responsible genes might be different from HNPCC. As X‐ray exposure promoted carcinogenesis of GIT in adult Mlh1–/– mice, an increased risk of secondary cancers after radiotherapy for HNPCC patients should be taken into consideration.
Deletion mapping of chromosome 13q in head and neck squamous cell carcinoma in Indian patients: correlation with prognosis of the tumour
Authors: Golam Sabbir Md. , Roy Anup , Mandal Syamsundar , Dam Aniruddha , Roychoudhury Susanta , Panda Chinmay Kumar 
Published: March 2006

SummaryDeletions in chromosome (chr.) 13q occur frequently in head and neck squamous cell carcinoma (HNSCC). Previous studies failed to identify common deleted regions in chr.13q, though several candidate tumour suppressor genes (TSGs) loci, e.g. BRCA2, RB1 and BRCAX have been localized in this chromosome, as well as no prognostic significance of the deletion has been reported. Thus, in the present study, deletion mapping of chr. 13q has been done in 55 primary HNSCC samples of Indian patients using 11 highly polymorphic microsatellite markers of which three were intragenic to BRCA2 gene, one intragenic to RB1 gene and another from BRCAX locus. The deletion in chr.13q was significantly associated with progression of HNSCC. High frequencies (27–39%) of loss of heterozygosity were found in 13q13.1 (BRCA2), 13q14.2 (RB1), 13q21.2–22.1 (BRCAX) and 13q31.1 regions. Deletions in the BRCA2 and RB1 regions were significantly correlated. The four highly deleted regions were associated with clinical stage and histological grades of the tumour as well as poor patient outcome. Deletion in the 13q31.1 region was only found to be associated with HPV infection. High frequencies (11–23%) of microsatellite size alteration (MA) were seen to overlap with the highly deleted regions. Forty per cent of the samples showed rare biallelic alteration whereas loss of normal copy of chromosome 13q was seen in five tumours. Thus, it seems that the putative TSGs located in the BRCAX and 13q31.1 regions as well as the BRCA2 and RB1 genes may have some cumulative effect in progression and poor prognosis of HNSCC. Significant association between deletion in BRCA2 and RB1 gene loci may indicate functional relationship between the genes in this tumour progression.
Development of diabetes in non‐obese diabetic mice promotes Chlamydia pneumoniae dissemination from lung to peripheral blood
Authors: Yamaguchi Hiroyuki , Oshio Ichiro , Osaki Takako , Kurata Satoru , Yamamoto Yoshimasa , Kamiya Shigeru 
Published: March 2006

SummaryWe examined a possible association between development of diabetes in non‐obese diabetic (NOD) mice and dissemination of Chlamydia (Chlamydophila) pneumoniae from lung to peripheral blood. By real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) with primers for C. pneumoniae 16S rRNA, following multiple intranasal inoculations, we detected bacteria in lung in NOD mice with diabetes (38.5%) as well as Institute of Cancer Research, USA (ICR) mice (40%), but prevalence of bacteria in NOD mice without diabetes (pre‐diabetic NOD mice and non‐diabetic retired NOD mice) was very low (4.8%). The bacteria were only detected in peripheral blood mononuclear cells (PBMCs) cultured with hydrocortisone of the NOD mice with diabetes (53.8%). Results of immunostaining with fluorescein isothiocyanate‐conjugated antichlamydia monoclonal antibody also showed the presence of bacterial antigens in the lungs and the PBMCs judged as positive by the RT‐PCR. However, C. pneumoniae from cultured PBMCs of all NOD mice was undetected by cultivation method with inclusion‐forming units assay. In addition, no influence of C. pneumoniae intranasal inoculation on development of diabetes in NOD mice was confirmed. Thus, the development of diabetes in NOD mouse appears to be one of critical factors for promoting the dissemination of C. pneumoniae from lung to peripheral blood.
The role of melatonin in immuno‐enhancement: potential application in cancer
Authors: Miller Sandra C. , Pandi Perumal S. R. , Esquifino Ana I. , Cardinali Daniel P. , Maestroni Georges J. M. 
Published: March 2006

SummaryMelatonin, a neurohormone produced mainly by the pineal gland, is a modulator of haemopoiesis and of immune cell production and function, both in vivo and in vitro. Physiologically, melatonin is associated with T‐helper 1 (Th1) cytokines, and its administration favours Th1 priming. In both normal and leukaemic mice, melatonin administration results in quantitative and functional enhancement of natural killer (NK) cells, whose role is to mediate defenses against virus‐infected and cancer cells. Melatonin appears to regulate cell dynamics, including the proliferative and maturational stages of virtually all haemopoietic and immune cells lineages involved in host defense – not only NK cells but also T and B lymphocytes, granulocytes and monocytes – in both bone marrow and tissues. In particular, melatonin is a powerful antiapoptotic signal promoting the survival of normal granulocytes and B lymphocytes. In mice bearing mid‐stage leukaemia, daily administration of melatonin results in a survival index of 30–40% vs. 0% in untreated mice. Thus, melatonin seems to have a fundamental role as a system regulator in haemopoiesis and immuno‐enhancement, appears to be closely involved in several fundamental aspects of host defense and has the potential to be useful as an adjuvant tumour immunotherapeutic agent.
The mechanisms of carbon monoxide production by inhalational agents
Authors: Coppens M. J. , Versichelen L. F. M. , Rolly G. , Mortier E. P. , Struys M. M. R. F. 
Published: March 2006

SummaryCarbon monoxide can be formed when volatile anaesthetic agents such as desflurane and sevoflurane are used with anaesthetic breathing systems containing carbon dioxide absorbents. This review describes the possible chemical processes involved and summarises the experimental and clinical evidence for the generation of carbon monoxide. We emphasise the different conditions that were used in the experimental work, and explain some of the features of the clinical reports. Finally, we provide guidelines for the prevention and detection of this complication.
Protein cross‐contamination during batch cleaning and autoclaving of the ProSeal™ laryngeal mask airway
Authors: Richards E. , Brimacombe J. , Laupau W. , Keller C. 
Published: March 2006

SummaryWe tested the hypothesis that protein cross‐contamination occurs during batch cleaning and autoclaving of a reusable extraglottic airway device, the ProSeal™ laryngeal mask airway. At the end of each day for 10 days, nine laryngeal mask airways that had been used for non‐intra‐oral surgery were cleaned and autoclaved alongside a new unused laryngeal mask airway. In addition, a new unused laryngeal mask airway underwent the same cleaning and autoclaving procedures in isolation. Protein staining was more frequently detected on the unused laryngeal mask airways that were processed by batch rather than in isolation (p < 0.01). Protein staining was detected on all unused laryngeal mask airways that were processed by batch, but none on those processed in isolation. Protein staining was more severe with the used compared with the unused laryngeal mask airways (p < 0.001). We conclude that protein cross‐contamination of the laryngeal mask airway occurs during batch cleaning and autoclaving and recommend that reusable airway devices are cleaned in isolation.
Diverse niches within multiple myeloma bone marrow aspirates affect plasma cell enumeration
Authors: Nadav Liat , Katz Ben‐Zion , Baron Shoshana , Yossipov Lydia , Polliack Aaron , Deutsch Varda , Geiger Benjamin , Naparstek Ellizabeth 
Published: March 2006

SummaryA basic criterion for the diagnosis of multiple myeloma is plasma cell enumeration within the bone marrow (BM). This report showed that flow cytometry under‐estimated the number of plasma cells in BM aspirates by an average of 60%, compared with morphological evaluation. The discrepancy was partially because BM smears contain cells associated with the lipid‐enriched spicules. In contrast, flow cytometry is performed on the BM fluid, which is depleted of the lipid‐adhesive plasma cells. This discrepancy may point to different plasma cell subpopulations associated with diverse niches within the BM.
Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF‐β/BMP pathway
Authors: Nolan Vikki G. , Adewoye Adeboye , Baldwin Clinton , Wang Ling , Ma Qianli , Wyszynski Diego F. , Farrell John J. , Sebastiani Paola , Farrer Lindsay A. , Steinberg Martin H. 
Published: March 2006

SummaryCutaneous leg ulcers are common in sickle cell anaemia and their risk might be genetically determined. Sickle cell anaemia patients were studied to examine the relationship of leg ulcers with haemolysis and with single nucleotide polymorphisms (SNPs) in candidate genes that could affect sickle vasoocclusion. Leg ulcer patients had lower haemoglobin levels and higher levels of lactate dehydrogenase, bilirubin, aspartate transaminase and reticulocytes than did control patients with sickle cell anaemia but without leg ulcers. Age‐adjusted comparisons showed that sickle cell anaemia‐α thalassaemia was more frequent among controls than cases. These results strongly suggested that the likelihood of having leg ulcers was related to the intensity of haemolysis. 215 SNPs in more than 100 candidate genes were studied. Associations were found with SNPs in Klotho, TEK and several genes in the TGF‐β/BMP signalling pathway by genotypic association analyses. KL directly or indirectly promotes endothelial nitric oxide (NO) production and the TEK receptor tyrosine kinase is involved in angiogenesis. The TGF‐β/BMP signalling pathway modulates wound healing and angiogenesis, among its other functions. Haemolysis‐driven phenotypes, such as leg ulcers, could be improved by agents that reduce sickle erythrocyte density or increase NO bioavailability.
A review of the scientific and literary accomplishments of Professor R.G. Macfarlane CBE, FRS
Authors: Hougie Cecil 
Published: March 2006

SummaryThis article gives an account of some of the pioneer work of Professor R.G. Macfarlane CBE, FRS in haemostasis and fibrinolysis. His Cascade hypothesis, which together with the Waterfall, became the most cited of all papers on blood coagulation in the latter part of the 20th century, is described, together with its rebuttal and defence. Macfarlane had the gift of writing in elegant prose and his papers on the philosophy of science and his biographies of Lord Florey and Fleming are reviewed. The biography of Sir Alexander Fleming is a great work that deserves to be on the shelves of every library.
Haematopoietic stem cell transplantation as primary therapy of sporadic adult Burkitt lymphoma*
Authors: Song Kevin W. , Barnett Michael J. , Gascoyne Randy D. , Horsman Douglas E. , Forrest Donna L. , Hogge Donna E. , Lavoie Julyle C. , Nantel Stephen H. , Nevill Thomas J. , Shepherd John D. , Smith Clayton A. , Sutherland Heather J. , Voss Nicholas J. , Toze Cynthia L. , Connors Joseph M. 
Published: March 2006

SummaryHigh dose chemoradiotherapy and haematopoietic stem cell transplantation (SCT) is used as primary therapy for patients diagnosed with Burkitt lymphoma (BL). Forty‐three adults presented with sporadic BL in British Columbia between 1987 and 2003. Twenty patients had bone marrow involvement. Sixteen patients did not proceed to SCT because of chemorefractory disease (n = 9) or other reasons (n = 7). Twenty‐seven patients proceeded to SCT and had a 3‐year event‐free survival of 51%. In conclusion, approximately 50% of patients with chemosensitive BL who undergo SCT can be cured; however, a significant number of patients will not proceed to SCT because of early resistance or recurrence.