bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertainty of knee joint muscle activity during knee joint torque exertion: the significance of controlling adjacent joint torque
Authors: Nozaki Daichi , Nakazawa Kimitaka , Akai Masami
Published: April 2005

In the single-joint torque exertion task, which has been widely used to control muscle activity, only the relevant joint torque is specified. However, the neglect of the neighboring joint could make the procedure unreliable, considering our previous result that even monoarticular muscle activity level is indefinite without specifying the adjacent joint torque. Here we examined the amount of hip joint torque generated with knee joint torque and its influence on the activity of the knee joint muscles. Twelve healthy subjects were requested to exert various levels of isometric knee joint torque. The knee and hip joint torques were obtained by using a custom-made device. Because no information about hip joint torque was provided to the subjects, the hip joint torque measured here was a secondary one associated with the task. The amount of hip joint torque varied among subjects, indicating that they adopted various strategies to achieve the task. In some subjects, there was a considerable internal variability in the hip joint torque. Such variability was not negligible, because the knee joint muscle activity level with respect to the knee joint torque, as quantified by surface electromyography (EMG), changed significantly when the subjects were requested to change the strategy. This change occurred in a very systematic manner: in the case of the knee extension, as the hip flexion torque was larger, the activity of mono- and biarticular knee extensors decreased and increased, respectively. These results indicate that the conventional single knee joint torque exertion has the drawback that the intersubject and/or intertrial variability is inevitable in the relative contribution among mono- and biarticular muscles because of the uncertainty of the hip joint torque. We discuss that the viewpoint that both joint torques need to be considered will bring insights into various controversial problems such as the shape of the EMG-force relationship, neural factors that help determine the effect of muscle strength training, and so on.
Muscle sarcoplasmic reticulum Ca2+cycling adaptations during 16 h of heavy intermittent cycle exercise
Authors: Holloway G. P. , Green H. J. , Duhamel T. A. , Ferth S. , Moule J. W. , Ouyang J. , Tupling A. R.
Published: April 2005

The repetition-dependent effects of a repetitive heavy exercise protocol previously shown to alter muscle mechanic behavior (Green HJ, Duhamel TA, Ferth S, Holloway GP, Thomas MM, Tupling AR, Rich SM, and Yau JE. J Appl Physiol 97: 2166–2175, 2004) on muscle sarcoplasmic reticulum (SR) Ca2+-transport properties, measured in vitro, were examined in 12 untrained volunteers [peak aerobic power (V̇o2 peak) = 44.3 ± 0.66 ml·kg−1·min−1]. The protocol involved 6 min of cycle exercise performed at ∼91% V̇o2 peakonce per hour for 16 h. Tissue samples were obtained from the vastus lateralis before (B) and after (A) exercise at repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). Reductions ( P < 0.05) in maximal Ca2+-ATPase activity ( Vmax) of 26 and 12% with exercise were only observed at R1 and R16, respectively. Vmaxremained depressed ( P < 0.05) at R2 (B) but not at R9 (B) and R16 (B). No changes were observed in two other kinetic properties of the enzyme, namely the Hill coefficient (defined as the slope of the relationship between Ca2+-ATPase activity and free Ca2+concentration) and the Ca50(defined as the free Ca2+concentration needed to elicit 50% Vmax). Changes in Ca2+uptake (measured at 2,000 nM) with exercise and recovery generally paralleled Vmax. The apparent coupling ratio, defined as the ratio between Ca2+uptake and Vmax, was unaffected by the intermittent protocol. Reductions ( P < 0.05) in phase 1 Ca2+release (32%) were only observed at R1. No differences were observed between B and A for R2, R9, and R16 or between B and B for R1, R2, R9, and R16. The changes in phase 2 Ca2+release were as observed for phase 1 Ca2+release. It is concluded that the SR Ca2+-handling properties, in general, display rapid adaptations to repetitive exercise.
Myosin Loss in Denervated Rat Soleus Muscle after Dexamethasone Treatment
Authors: Horinouchi Hideo , Kumamoto Toshihide , Kimura Noriyuki , Ueyama Hidetsugu , Tsuda Tomiyasu
Published: April 2005

Objective: Critical illness myopathy (CIM) is an acute myopathy that appears in the setting of critical illness or during exposure to corticosteroids and neuromuscular blocking agents. Its pathological feature is selective loss of thick myosin filaments. Our aim is to gain further insight into the pathomechanism of myosin loss in this myopathy. Methods: To clarify the expression of myosin heavy chain (MHC) and ubiquitin ligase atrogin-1 in this myopathy, histological, immunohistochemical, SDS-PAGE, and semiquantitative reverse transcriptase-polymerase chain reaction studies were performed on innervated and denervated rat soleus muscles after saline and dexamethasone treatments. Results: Denervated muscles from dexamethasone-treated rats showed marked MHC loss. The mRNA expression of ubiquitin ligase atrogin-1 was significantly increased in denervated dexamethasone-treated muscles, suggesting that the ubiquitin-proteasome pathway plays an important role in muscular wasting in CIM. Furthermore, mRNA levels of MHC I, a myosin isoform, were decreased in the denervated dexamethasone-treated muscles. Conclusion: Our findings suggest that an altered transcription rate of myosin, as well as the upregulation of multiple ubiquitin ligases, may be responsible for selective myosin loss in this myopathy.
Glycyrrhizin Inhibits R5 HIV Replication in Peripheral Blood Monocytes Treated with 1-Methyladenosine
Authors: Takei Miwa , Kobayashi Makiko , Li Xiao-Dong , Pollard Richard B. , Suzuki Fujio
Published: April 2005

R5 HIV replicated in freshly isolated human peripheral blood monocytes after treatment with 1-methyladenosine (fresh PBM/MA), an immunosuppressive compound isolated from tumorous ascites fluids, while viral replication was not demonstrated in untreated peripheral blood monocytes (fresh PBM). The R5 HIV replication in fresh PBM/MA was inhibited by glycyrrhizin (GL). Without any other stimulation, fresh PBM/MA produced CCL2 and IL-10, while these soluble factors were not released from fresh PBM. GL greatly inhibited the production of CCL2 and IL-10 in fresh PBM/MA. After treatment with CCL2 and/or IL-10, CCR5 mRNA expression in fresh PBM was markedly enhanced, while only a trace level of the mRNA expression was detected in these cells in the absence of CCL2 or IL-10. CCR5 mRNA expression in fresh PBM treated with CCL2 or IL-10 was clearly inhibited by GL. These results indicate that GL inhibits R5 HIV replication in fresh PBM/MA through the inhibiting CCR5 expression mediated by CCL2 or IL-10.
Cytochemical Analysis of Pancreatic Islet Lipoapoptosis: Hyperlipidemia-Induced Cytoinvolution following Expression of the Diabetes (db/db) Mutation
Authors: Garris David R.
Published: April 2005

The diabetes (db/db) genotype mutation induces a hyperglycemic-hyperinsulinemic endometabolic state in C57BL/KsJ mice, manifesting a type II NIDDM diabetes-obesity syndrome (DOS) associated with intrinsic leptin receptor expression defects. The severity of the DOS-induced premature pancreatic dysfunction and cytoatrophic involution has been linked to the severity of hypercytolipidemia which develops in pancreatic islets following systemic lipoidosis. The current studies define the cytochemical changes associated with pancreatic islet and acinar vesicular degranulation (deproteinization), cytoinvolution and B-cell dysfunction relative to the onset of cellular (nuclear DNA fragmentation) apoptosis in 20- to 26-week-old chronic db/db mutants relative to control (+/?) indices. The db/db mutation induced dramatic increases in body weights, blood glucose as well as serum and tissue triglyceride concentrations relative to +/? parameters. In contrast, pancreatic tissue weights and insulin concentrations were significantly decreased in db/db groups in association with premature islet cytoatrophy relative to +/? indices. Concurrent elevations in db/db tissue triglyceride concentrations and islet cytolipid depositions accompanied the progressive pancreatic cytoatrophic alterations. Diminished B-cell vesicular (insulin) granulation was pronounced in atrophic pancreatic islets, which were also characterized by hyperplasic acinar cellular intrusion and subsequent proteolytic B-cell dissolution coincident with 3′-DNA fragmentation-indexed (TUNEL-labeled) nuclear apoptosis. The chronic expression of the db/db mutation exacerbated these pancreatic islet B-cell atrophy indices, characterized by insulin vesicular degranulation, suppressed systemic insulin concentrations, invasive hypercytolipidemia, progressive cellular atrophy and hyperplasic acinar proteolytic dissolution, culminating in islet volume/mass reduction and chronic db/db-related pancreatic involution. The results of these studies indicate that pancreatic islet B-cell apoptosis is coincident with the progressive hypercytolipidemia component of the type II DOS promoted by the db/db genotypic mutation. These data suggest that the severity of progressive pancreatic lipoapoptosis disrupts regulatory cellular metabolic cascades, resulting in nuclear fragmentation, organelle dissolution and the subsequent promotion of a nonhomeostatic cytochemical milieu which ultimately renders islet B-cell populations susceptible to acinar proteolytic dissolution and progressive pancreatic involution.
A Single Nucleotide Polymorphism in the 5′ Untranslated Region of the EGF Gene Is Associated with Occurrence and Malignant Progression of Gastric Cancer
Authors: Hamai Yoichi , Matsumura Shunji , Matsusaki Keisuke , Kitadai Yasuhiko , Yoshida Kazuhiro , Yamaguchi Yoshiyuki , Imai Kazue , Nakachi Kei , Toge Tetsuya , Yasui Wataru
Published: April 2005

Objective: Epidermal growth factor (EGF) has many biological functions and plays an important role in the progression of various tumors including gastric cancer. An A-G single nucleotide polymorphism (SNP) at position 61 in the 5′-untranslated region (UTR) of the EGF gene has recently been reported to be associated with different levels of EGF production. We examined whether this polymorphism is correlated with the development and malignant phenotypes of gastric cancer. Methods: The study population included 200 gastric cancer patients and 230 healthy control subjects. The SNP in the 5′-UTR of the EGF gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results: The A allele was significantly less frequent in patients than in controls (p = 0.01). Individuals with the A/A or A/G genotype showed a significantly lower risk of gastric cancer than those with the G/G genotype [adjusted odds ratio (OR) = 0.56], whereas the same genotypes were associated with malignant progression of this cancer, e.g. deeper tumor invasion, increased lymph node metastasis and advanced clinical stage, and histological classification in gastric cancer patients (adjusted OR = 1.80, 1.98, 2.26 and 1.89, respectively). Conclusions: Our findings suggest that the A-G polymorphism of EGF is involved not only in the occurrence but also in the malignant progression of gastric cancer.
The Expression Pattern of UDP-N-Acetyl-α-D-Galactosamine-Polypeptide N-Acetyl-Galactosaminyl Transferase-3 in Squamous Cell Carcinoma of the Esophagus
Authors: Ishikawa Makoto , Kitayama Joji , Kohno Kimitoshi , Nagawa Hirokazu
Published: April 2005

Objective: UDP-N-acetyl-α-D-galactosamine-polypeptide N-acetylgalactosaminyl transferase-3 (GalNAc-T3) regulates the initial glycosylation of mucin-type O-linked proteins. Although a different expression of GalNAc-T3 has been reported in various cancers, the expression has not been characterized in squamous cell carcinoma (SCC) of the esophagus. Methods: We have also evaluated the expression of this enzyme in surgically resected esophageal mucosa. By immunohistochemical staining using a specific antibody, we evaluated the expression of GalNAc-T3 in 66 esophageal SCC and 28 dysplasia samples, and analyzed the relationship between the expression of GalNAc-T3 and clinicopathological features. Results: GalNAc-T3 was positively detected in the majority of the cases of SCC, but not in dysplasia as well as the normal counterparts in resected esophagus. GalNAc-T3 was determined to be positive in 37 cases (68.5%) of differentiated carcinomas, but only in 4 cases (33.3%) of undifferentiated carcinomas (p < 0.05). Hematogeneous metastasis was observed in 13 of 41 (31.7%) GalNAc-T3-positive tumors, which was significantly more frequent than in negative tumors (2/25, 8%; p < 0.05). The number of metastatic nodes was significantly higher in tumors with GalNAc-T3-positive than GalNAc-negative expression (4.2 ± 3.2 vs. 2.8 ± 1.3, p < 0.05). The survival rate tended to be lower for patients with GalNAc-T3-positive tumors, although the difference was not statistically significant (p = 0.18). Conclusion: GalNAc-T3 may play a positive role in the process of carcinogenesis and progression in esophageal SCC. Functional inhibition of GalNAc-T3 may be effective for the prevention and treatment of esophageal SCC.
Alteration of Gene Expression in Intervertebral Disc Degeneration of Passive Cigarette- Smoking Rats: Separate Quantitation in Separated Nucleus pulposus and Annulus fibrosus
Authors: Ogawa Takeshi , Matsuzaki Hiromi , Uei Hiroshi , Nakajima Shinya , Tokuhashi Yasuaki , Esumi Mariko
Published: April 2005

Objective: We constructed a passive cigarette-smoking model with rats to investigate the molecular mechanism of intervertebral disc degeneration, and foundby gene expression analysis that passive cigarette smoking stimulated the stress-responsive signal pathway and inhibited the apoptotic pathway. In this study, to clarify that these changes were derived from either nucleus pulposus (NP) or annulus fibrosus (AF), we separately collected NP and AF and quantitatively analyzed gene expression. Methods: Total RNA was extracted from NP and AF of the lumbar intervertebral discs from rats which were kept in a smoking box for 4 and 8 weeks. Gene expression was measured by real-time PCR of cDNA synthesized from the total RNA. Results: Stress-responsive protein, heat shock protein 70, was expressed similarly in NP and AF, and wasupregulated to the same degree after 8 weeks of passive cigarette smoking. The protein tyrosine phosphatase gene was expressed more strongly in AF than in NP, and wasupregulated after 8 weeks of smoking in both tissueparts. The type II collagen and aggrecan genes were predominantly expressed in AF and NP, respectively. Conclusion: These results indicate that passive cigarette smoking stimulates both NP and AF, and induces the stress-responsible genes such as heat shock protein 70 and protein tyrosine phosphatase in both.
Clinical Importance of Transforming Growth Factor-β but Not of Tumor Necrosis Factor-α Gene Polymorphisms in Patients with the Myelodysplastic Syndrome Belonging to the Refractory Anemia Subtype
Authors: Balog Attila , Borbényi Zita , Gyulai Zsófia , Molnár Lenke , Mándi Yvette
Published: April 2005

Objectives: Tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) are cytokines that play key roles in the myelodysplastic syndrome (MDS). There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-β1 protein, located in codon 10 in exon 1 and in the –308 promoter region of TNF-α. The objective of this study was to investigate the association between TNF-α and TGF-β1 gene polymorphisms and the susceptibility to MDS and the progression of the disease among patients with MDS belonging to the refractory anemia (RA) subtype. Methods: The diagnosis of MDS (n = 50) was based on the FAB criteria. The TNF-α genotypes were analyzed by PCR-RFLP and the TGF-β genotypes were analyzed using an amplification refractory mutation system. Results and Conclusions: Compared with healthy control subjects, patients with RA showed no significant deviations in genotype or allele frequencies of TNF-α. The TT homozygosity at codon 10 of TGF-β1 was significantly higher among patients with bi- or pancytopenia (severe group) than in the patients with anemia only (mild group; odds ratio = 6.99, p = 0.003). These findings suggest that the TGF-β1 gene polymorphism in codon 10 and the –308 TNF-α gene polymorphism do not predispose to the development of RA, but the TGF-β1 gene polymorphism may affect disease progression.
HLA-DR Binding Prediction and Experimental Evaluation of T-Cell Epitopes of Mycolyl Transferase 85B (Ag85B), a Major Secreted Antigen of Mycobacterium tuberculosis
Authors: Mustafa Abu S. , Abal Adnan T. , Shaban Fatma , El-Shamy Abdulsalam M. , Amoudy Hanady A.
Published: April 2005

Objective: To identify T-cell epitopes of Ag85B by analysis of its sequence for prediction to bind HLA-DR alleles and evaluate the predicted peptides for recognition by T cells in antigen-induced proliferation assays. Materials/Subjects and Methods: The complete sequence of Ag85B was analyzed for HLA-DR binding prediction to 51 HLA-DR alleles by using a virtual matrix-based prediction program (ProPred). Synthetic peptides covering the sequence of mature Ag85B were also analyzed for binding to HLA-DR alleles, and evaluated for recognition in antigen-induced proliferation assays with Ag85B-specific T-cell lines established from the peripheral blood mononuclear cells of 10 HLA-DR-heterogeneous tuberculosis patients. Results: The ProPred analysis of the full-length Ag85B (325 aa), signal peptide (40 aa) and the mature protein (285 aa) predicted their binding to 100, 76 and 98% of the 51 HLA-DR alleles, respectively. The analysis of 31 synthetic peptides for binding to HLA-DR alleles showed that 4 of them could bind >50% HLA-DR alleles, and were considered promiscuous. Testing of Ag85B-specific T-cell lines with synthetic peptides showed that all of the T-cell lines responded to one or more peptides of Ag85B, and 9 of the 10 cell lines responded to one or more of the four peptides considered promiscuous for binding to HLA-DR alleles. Conclusion: The ProPred program was useful in predicting the HLA-DR alleles binding regions of Ag85B and identifying the promiscuous peptides recognized by T cells.
Comparison of Postoperative Hepatic Function between Laparoscopic and Open Cholecystectomy
Authors: Hasukic Sefik , Kosuta Dragutin , Muminhodzic Kasim
Published: April 2005

Objective: In this prospective study, we evaluated the effects of pneumoperitoneum on hepatic function during laparoscopic (LC) and open cholecystectomy (OC). Subjects and Methods: One hundred patients who underwent LC (n = 50) or OC (n = 50) were included in the study. The groups were similar in age, sex, weight and height. Following liver function tests (total bilirubin; γ-glutamyltransferase, GGT; alkaline phosphatase, ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were obtained preoperatively and at 24 and 48 h postoperatively. Similar anesthesiologic protocol was used for both LC and OC. During LC, the intra-abdominal pressure was maintained within the conventional range of 12–14 mm Hg. Results: Total bilirubin, ALP, GGT and LDH levels remained unchanged from baseline in both groups without significant difference between them. A higher number of patients had increased values of ALT (26/50 vs. 5/50) and AST (23/50 vs. 6/50) in LC compared to OC group. Although the difference was statistically significant (p < 0.000 for ALT and p = 0.0004 for AST) the increased level decreased at 48 compared to 24 h. Conclusion: The results indicate that LC is associated with transient elevation of ALT and AST. The disturbances in the function of the liver after LC are self-limited and not associated with any morbidity in patients with a normal liver function.
Dual Modality of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Patients with Cervical Carcinoma of Unknown Primary
Authors: Freudenberg Lutz S. , Fischer Markus , Antoch Gerald , Jentzen Walter , Gutzeit Andreas , Rosenbaum Sandra J. , Bockisch Andreas , Egelhof Thomas
Published: April 2005

Objective: To evaluate an optimized F-18-flurodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) acquisition protocol for head and neck cancer and assess the usefulness of combined FDG-PET/CT in locating unknown primary tumors in patients with biopsy-proven cervical lymph node metastases. Subjects and Methods: Twenty-one patients with cervical lymph node metastases of unknown primary tumors underwent staging with FDG-PET/CT. The images of FDG-PET alone, CT alone, FDG-PET/CT read side by side and fused and FDG-PET/CT were evaluated separately by 2 physicians. Imaging results were correlated with either histology (n = 14) or clinical follow-up (n = 7). Results: On the fused FDG-PET/CT images, primary tumors were identified in 12 patients (57%); with FDG-PET alone and FDG-PET and CT read side by side 11 (52%) primary tumors were found while CT alone identified 5 (23%) primary tumors. Conclusion: Our data indicate that fused FDG-PET and CT images increased the sensitivity of detecting carcinoma of unknown primary (CUP) tumors compared to CT alone, but not to FDG-PET alone or FDG-PET and CT read side by side. Hence accurate fusion of functional and morphologic data by FDG-PET/CT is a promising imaging modality in the clinical workup of patients with cervical CUP tumors.
Evaluating Diabetic Foot Infection with Magnetic Resonance Imaging: Kuwait Experience
Authors: Al-Khawari Hanaa A. , Al-Saeed Osama M. , Jumaa Taleb H. , Chishti Fayaz
Published: April 2005

Objective: The aim of this study was to evaluate the capability of magnetic resonance imaging (MRI) to depict and characterize the changes seen in diabetic foot infections. Subjects and Methods: MRI studies of 29 diabetic patients with suspected foot infection were evaluated. Sagittal and transverse T1-weighted images before and after intravenous gadolinium, and transverse fat-suppressed T2-weighted images were performed on the affected regions. The MRI findings were compared to subsequent clinical and/or histopathological findings. Results: The MRI findings were: osteomyelitis in 14 patients, abscess in 5, cellulitis in 26, tenosynovitis in 4 and neuropathic joint in 8. Three cases were normal. Pathological confirmations were obtained in 19 patients. MRI and histological diagnosis were in concordance in 79% of osteomyelitis cases, 100% of neuropathy cases and 100% of cellulitis cases. The sensitivity and specificity of MRI in diagnosing osteomyelitis were 100 and 63%, respectively. The positive predictive and negative predictive values, and the accuracy were 79, 100 and 84%, respectively. MRI helped surgical planning for limb salvage procedures in 6 of the osteomyelitis cases and in a cellulitis case. Conclusion: The results indicate that MRI is a sensitive and accurate imaging modality for the evaluation of foot infections in diabetic patients and for planning proper treatment.
The Acute Scrotum: A Review of 40 Cases
Authors: Abul Fawzi , Al-Sayer Hilal , Arun Narayanaswamy
Published: April 2005

Objective: To determine the relative importance of clinical presentation, laboratory studies, and ultrasonography in the diagnosis of acute scrotum, and to suggest an effective method of management. Subjects and Methods: Forty patients who were hospitalized between January 2002 and December 2002 for acute scrotum were studied with respect to history, physical examination, blood tests, urine analysis including culture, and scrotal ultrasonography with color Doppler study. Results: Epididymitis (n = 24) was the commonest cause of acute scrotum followed by testicular torsion (n = 11), torsion of testicular appendages (n = 4), and idiopathic scrotal edema (n = 1). Both mean age (40.7 vs. 13.8 years), and average duration of pain at presentation (4.5 days vs. 19.1 h) were higher in patients with epididymitis than in torsion. Onset was usually insidious in epididymitis, sudden in testicular torsion, and variable in torsion of testicular appendages. The majority (87.5%) of patients with epididymitis were managed conservatively. The testis was salvaged in 81.8% of patients with testicular torsion. The accuracy of ultrasonography was only 72.7% in testicular torsion, but was good in epididymitis. Conclusion: Our results show that a careful clinical evaluation, by an experienced examiner, provides the correct diagnosis in acute scrotum rather than ultrasonography. It is of utmost importance to exclude testicular torsion in those who are younger than 16 years and whose pain duration is less than 24 h.
Reference Ranges of Lymphocyte Subsets of Healthy Adults in Turkey
Authors: Yaman Akgün , Çetiner Salih , Kibar Filiz , Taşova Yeşim , Şeydaoğlu Gülşah , Dündar İsmail H.
Published: April 2005

Abstract: The aim of this study was to determine the reference ranges of lymphocyte subsets in serologically HIV-negative healthy adults in Turkey. Materials and Methods: Blood samples from 220 healthy adults, 105 female and 115 male, collected into tubes containing EDTA were investigated for lymphocyte subsets using flow cytometry. The age range was 18–80 years (44.80 ± 16.69). Results: The mean percentage and absolute values of the lymphocyte subsets were as follows: CD3: 72.70 ± 8.44%, 1,680 ± 528 cells/µl; CD4: 47.37 ± 9.10%, 1,095 ± 391 cells/µl; CD8: 28.99 ± 5.99%, 669 ± 239 cells/µl; CD19: 10.96 ± 4.44%, 254 ± 122 cells/µl and CD56: 7.03 ± 3.26%, 161 ± 92 cells/µl, respectively. The ratio of CD4/CD8 was 1.68 ± 0.43. There was no statistically significant difference in the percentages and absolute values of lymphocyte subsets between the genders (p > 0.05). Conclusion: Immunophenotyping has been used to establish reference values of lymphocyte subsets in normal healthy adults in Turkey.
Acute Transient Cerebral Toxicity Associated with Administration of High-Dose Methotrexate
Authors: Mittal Rakesh , Mottl Hubert , Nemec Jaroslav
Published: April 2005

Objective: To report the first case of transient central nervous system toxicity after administration of high-dose methotrexate (HDMTX) in the Middle East. Clinical Presentation: A 10-year-old boy was diagnosed with osteosarcoma of the proximal end of the left tibia. He underwent primary amputation and was started on adjuvant chemotherapy, which included administration of HDMTX. He developed acute cerebral toxicity after the 5th dose of HDMTX in the form of diplopia, seizures and disorientation. He recovered completely without any complication or neurological sequelae. Conclusion: The acute cerebral toxicity associated with HDMTX was completely reversible and without any sequelae.
Transcriptional Activation of Nucleus tractus solitarii/Area postrema Catecholaminergic Neurons by Pharmacological Inhibition of Caudal Hindbrain Monocarboxylate Transporter Function
Authors: Patil Gopal D. , Briski Karen P.
Published: April 2005

Evidence that intracerebral lactate administration alters electrophysiological sensitivity of metabolic-signaling neurons and hypoglycemic counterregulation suggests that this substrate fuel is a monitored indicator of in central nervous system energy balance. Catecholaminergic (CA) neurons in the caudal hindbrain nucleus tractus solitarii (NTS)/area postrema (AP) complex participate in the origin and/or relay of stimuli that signal deficient glucose provision to the brain. The present studies evaluated the responsiveness of this neurochemical phenotype to lactate insufficiency by investigating the effects of pharmacological inhibition of local monocarboxylate transporter activity on the transcriptional status of these cells. Adult female rats were sacrificed by transcardial perfusion 2 h after infusion of graded doses of the monocarboxylate transporter inhibitor, α-cyano-4-hydroxycinnamic acid (4-CIN), or vehicle into the caudal fourth ventricle, and tissue sections through the NTS/AP were processed by dual-label immunofluorescence histochemistry for demonstration of cytoplasmic tyrosine hydroxylase (TH) and the inducible nuclear AP-1 regulatory factor, Fos. While vehicle administration resulted in negligible Fos immunostaining within the NTS, 4-CIN-treated animals exhibited dose-dependent increases in mean numbers of Fos-ir- and TH-/Fos-ir-positive neurons in this structure. These data show that pharmacological suppression of lactate trafficking in the caudal hindbrain elicits the genomic activation of NTS/AP CA neurons. In light of evidence implicating this neurochemical phenotype in signaling of cellular energy imbalance, the current results support the view that diminished uptake and/or catabolism of lactate may underlie CA neuronal activation of neural pathways governing compensatory behavioral and physiological responses to metabolic substrate deficiency.
Early Supported Discharge for Stroke Patients Improves Clinical Outcome. Does It Also Reduce Use of Health Services and Costs?
Authors: Fjaertoft Hild , Indredavik Bent , Magnussen Jon , Johnsen Roar
Published: April 2005

Background: An early supported discharge service (ESD) appears to be a promising alternative to conventional care. The aim of this trial was to compare the use of health services and costs with traditional stroke care during a one-year follow-up. Methods: Three hundred and twenty patients were randomly allocated either to ordinary stroke unit care or stroke unit care combined with ESD which was coordinated by a mobile team. The use of all health services was recorded prospectively; its costs were measured as service costs and represent a combination of calculated average costs and tariffs. Hospital expenses were measured as costs per inpatient day and adjusted for the DRG. Results: There was a reduction in average number of inpatient days at 52 weeks in favour of the ESD group (p = 0.012), and a non-significant reduction in total mean service costs in the ESD group (EUR 18,937/EUR 21,824). ESD service seems to be most cost-effective for patients with a moderate stroke. Conclusion: Acute stroke unit care combined with an ESD programme may reduce the length of institutional stay without increasing the costs of outpatient rehabilitation compared with traditional stroke care.
Gamma Knife Radiosurgery for Tumors Involving the Cavernous Sinus
Authors: Liu A-Li , Wang Chungcheng , Sun Shibing , Wang Meihua , Liu Peng
Published: April 2005

Objective: To study the features of diagnosis and radiosurgery of tumors involving the cavernous sinus. Methods: From December 1994 to the end of 2000, 175 patients with cavernous sinus lesions were treated by Leksell gamma knife (GK) in our Institute. Ninety patients (51.4%) had had open surgery previously. Our experience of treating cavernous sinus tumors by GK was analyzed retrospectively. Results: A Hundred and forty-four (82.3%) patients were followed from 1 to 84 months (median 32.5 months); total tumor control rate was 94%. Surgery was performed after radiosurgery in 3 patients because of tumor enlargement. Metastatic tumor in the cavernous sinus was highly sensitive to irradiation. These lesions shrunk markedly on MRI 2–3 months after GK surgery. The median survival time was 12.2 months, and patients died of noncavernous sinus lesions. Conclusion: With high tumor control rate and few complications, GK surgery could become a main option for small benign or residual tumors involving the cavernous sinus. It is also very useful as part of comprehensive therapy for metastatic tumors in the cavernous sinus.
The Klumpke Family – Memories by Doctor Déjerine, Born Augusta Klumpke
Authors: Bogousslavsky Julien
Published: April 2005

In this paper, we present a translation of an unpublished autobiographical document by Augusta Déjerine-Klumpke, reporting her early years before she came to Paris to study medicine, when she was able to become one of the first women in France to hold a hospital position, as an extern and an intern. This American-born girl later married Jules Déjerine, who was to become the second successor to Charcot at La Salpétrière 23 years later. The present document gives a vivid account on the preceding years, and emphasizes the extraordinary dynamism and enthusiasm of a young woman, whose efforts and contributions influenced neurology at the turn of the 20th century, and dramatically changed the role of women in medical careers.
Clinical Characteristics of Stroke Patients with Antiphospholipid Antibodies
Authors: Terashi Hiromi , Uchiyama Shinichiro , Hashimoto Shiori , Miyazaki Kazuhide , Tsutsumi Yukiko , Yamazaki Masako , Iwata Makoto
Published: April 2005

Background: Antiphospholipid syndrome is important as a cause of ischemic stroke, although clinical characteristics of the syndrome are not well documented. Methods: We analyzed differences in clinical characteristics between 40 antiphospholipid-antibody (aPL)-positive and 40 aPL-negative stroke patients. Results: Stroke patients with aPL were significantly younger and were more likely to be women in comparison with stroke patients without aPL. Valvular heart disease, neurological complications and hematological disorders were more frequent in the aPL-positive group. The mean value of thrombin-antithrombin III complex was significantly lower in the aPL-positive group. Cerebral infarctions in the carotid system were less and large-artery lesions more frequent in the aPL-positive patients. Conclusions: Stroke patients with aPL have clinical characteristics distinct from stroke patients without aPL.
Is the Measurement of Cerebral Microembolic Signals a Good Surrogate Marker for Evaluating the Efficacy of Antiplatelet Agents in the Prevention of Stroke?
Authors: Wong K.S. Lawrence
Published: April 2005

Stroke is difficult to treat with few treatment options. Until such time as appropriate therapeutic regimens are established, prevention, both in the primary and in the secondary setting, is of paramount importance. Evaluation of pharmacological agents for the prevention of stroke in conventional clinical studies has the advantage that the outcome parameter is a direct measure of efficacy, and the disadvantage that many patients must be recruited and many evaluations performed over an extended period to provide adequate statistical power, making such studies lengthy and costly. Measurement of cerebral microembolic signals (MES) using transcranial Doppler ultrasonography has been proposed as a useful surrogate end point to investigate new antiplatelet agents and to evaluate further the benefits of existing antiplatelet therapies. MES measurements may provide a means of more directly evaluating the pharmacological activity of an antiplatelet agent. However, does measurement of MES accurately predict efficacy in stroke prevention? This review evaluates recent studies where the relationship between MES and cerebral ischaemic events has been explored and studies where the effects of antiplatelet agents on MES rates have been investigated. Overall, there is a growing body of evidence to suggest that MES may be used as a surrogate marker for cerebral infarction and clinical events, thus allowing quick appraisal of the efficacy of antiplatelet agents. Studies currently in progress should provide further insight into the value of the measurement of MES in clinical studies in stroke prevention.
Persistent Elevation of C-Reactive Protein May Predict Cardiac Hypertrophy and Dysfunction in Patients Maintained on Hemodialysis
Authors: Kim Byung-Soo , Jeon Doo Soo , Shin Mi Jung , Kim Young Ok , Song Ho Cheol , Lee Seung Hun , Kim Suk Young , Choi Euy Jin , Chang Yoon Sik , Bang Byung Kee
Published: April 2005

Background: C-reactive protein (CRP), which reflects chronic inflammation, is a strong predictor of cardiovascular mortality in hemodialysis patients. We investigated whether persistent elevation of CRP is associatedwith cardiac function and morphology in patients maintained on hemodialysis. Methods: Predialysis high-sensitivity CRP (hs-CRP) was measured twice at an interval of 3 weeks in 52 stable hemodialysis patients, and echocardiographic studies were performed. Results: 25 patients showed persistent elevation of predialysis hs-CRP (>3 mg/l, high CRP group). Patients in the high CRP group had a lower dialysis dose (p < 0.01), higher troponin T (p < 0.01), and higher fibrinogen (p < 0.01). Echocardiographic studies showed that left atrial diameter (LA, p < 0.05), interventricular septal thickness (IVST, p < 0.05), left ventricular end-diastolic volume (LVEDV, p < 0.05), and left ventricular mass index (LVMI, p < 0.05) were higher in the high CRP group. However the ejection fraction (EF) was lower in the high CRP group (p < 0.05), which also contained more patients with low EF (<40%) (p < 0.01). There was no difference in diabetes mellitus, acute infection and type of vascular access between the groups. hs-CRP level was positively correlated with troponin T (r = 0.416, p < 0.01) and fibrinogen (r = 0.560, p < 0.001), and IVST with hs-CRP level (r = 0.291, p < 0.05), whereas the EF was negatively correlated with hs-CRP(r = –0.301, p < 0.05). In addition, the high CRP group correlated positively with IVST (r = 0.281, p < 0.05), LVEDV (r = 0.322, p < 0.05), and LVMI (r = 0.312, p < 0.05) and negatively with EF (r = –0.311, p < 0.05). On multivariate analysis, the high CRP group (β = –0.312, β = 0.238, and β = 0.318, respectively) was a significant predictor of EF (R = 0.62, p = 0.025), LVMI (R = 0.928, p = 0.02) and IVST (R = 0.64, p = 0.01). Conclusions: Persistent elevation of CRP, which is an independent risk factor for EF, LVMI and IVST, may predict cardiac hypertrophy and dysfunction in patients maintained on hemodialysis.
Niche-Dependent Translineage Commitment of Endothelial Progenitor Cells, Not Cell Fusion in General, Into Myocardial Lineage Cells
Authors: Murasawa Satoshi , Kawamoto Atsuhiko , Horii Miki , Nakamori Shuko , Asahara Takayuki
Published: April 2005

Objective—

Previous studies from our laboratory have shown therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial ischemia. Our purpose was to investigate the mechanisms regulating EPC contribution to myocardial regeneration.

Methods and Results—

To evaluate niche-dependent expression profiles of EPCs in vitro, we performed coculture using cultured EPCs derived from human peripheral blood and rat cardiac myoblast cell line (H9C2). Reverse-transcription polymerase chain reaction (PCR) disclosed the expression of human-specific cardiac markers as well as human-specific smooth muscle markers. Cytoimmunochemistry presented several cocultured cells stained with human specific cardiac antibody. To prove this translineage differentiation in vivo, human cultured EPCs were injected into nude rat myocardial infarction model. Reverse-transcription PCR as well as immunohistochemistry of rat myocardial samples demonstrated the expression of human specific cardiac, vascular smooth muscle, and endothelial markers. We observed the distribution of colors (Qtracker; Quantum Dot Corp) in coculture to detect the fused cells, and the frequency of cell fusion was <1%.

Conclusions—

EPCs can contribute to not only vasculogenesis but also myogenesis in the ischemic myocardium in vivo. Transdifferentiation, not cell fusion, is dominant for EPCs commitment to myocardial lineage cells. Ex vivo expanded EPCs transplantation might have enhanced therapeutic potential for myocardial regeneration.
NADPH Oxidase–Dependent Superoxide Production Is Associated With Carotid Intima-Media Thickness in Subjects Free of Clinical Atherosclerotic Disease
Authors: Zalba Guillermo , Beloqui Oscar , José Gorka San , Moreno María U. , Fortuño Ana , Díez Javier
Published: April 2005

Objective—

Oxidative stress plays a critical role in the pathogenesis of atherosclerosis. The NADPH oxidase constitutes the main source of superoxide in phagocytic and vascular cells. This study aimed to investigate the levels of NADPH oxidase–mediated superoxide production in phagocytic cells and the association between phagocytic superoxide production and carotid intima-media thickness (IMT), a surrogate marker of asymptomatic atherosclerosis.

Methods and Results—

NADPH oxidase–mediated superoxide production was determined by a chemiluminescence assay using lucigenin and associated with IMT for 184 asymptomatic subjects free of overt clinical atherosclerotic disease. Compared with individuals in the lowest tertile of superoxide production, those in the upper tertile (>20 counts/sec) showed significantly higher IMT (
P
<0.05). In correlation analysis, a positive relationship was found between superoxide production and carotid IMT. Superoxide production also correlated positively (
P
<0.05) with body mass index (BMI). In multivariate analysis, the association of superoxide production with carotid IMT remained significant after adjustment for age, sex, systolic blood pressure, BMI, triglycerides, glucose, and smoking.

Conclusions—

In a population sample of adults without clinically overt atherosclerotic disease, increased NADPH oxidase activity was associated with enhanced carotid IMT, suggesting a relationship between phagocytic NADPH oxidase–mediated oxidative stress and the development of atherosclerosis.
Smad7 Gene Transfer Attenuates Adventitial Cell Migration and Vascular Remodeling After Balloon Injury
Authors: Mallawaarachchi Chandike M. , Weissberg Peter L. , Siow Richard C.M.
Published: April 2005

Objective—

Migration of adventitial fibroblasts contributes to arterial remodeling after angioplasty. This study used vascular gene transfer of smad7 to investigate whether antagonism of transforming growth factor-β1 signaling alters luminal loss and adventitial cell migration after balloon injury in rat carotid arteries.

Methods and Results—

Adenoviruses coordinating expression of β-galactosidase (β-gal) and smad7 or β-gal and green fluorescent protein (GFP) were applied to the perivascular surface of common carotid arteries. Balloon injury was performed 4 days after gene transfer, and animals were killed at 3, 7, and 14 days after injury. Uninjured arteries only expressed adventitial β-gal positive cells; however, after balloon injury in β-gal- and GFP-transfected arteries, β-gal-positive cells were observed within the medial layer of vessels and contributed to the population of cells within the neointima at 7 to 14 days. Overexpression of smad7 and β-gal resulted in a significant reduction in the number of β-gal–labeled cells in the neointima, concomitant with reduced luminal loss and decreased adventitial collagen content.

Conclusions—

We provide the first evidence that vascular smad7 overexpression attenuates remodeling and contribution of adventitial fibroblasts to neointima formation after balloon angioplasty. Smad7 may represent a novel therapeutic target to reduce the incidence of restenosis.
Genotype and Plasma Concentration of Cystatin C in Patients With Coronary Heart Disease and Risk for Secondary Cardiovascular Events
Authors: Loew Michael , Hoffmann Michael M. , Koenig Wolfgang , Brenner Hermann , Rothenbacher Dietrich
Published: April 2005

Objective—

Cysteine proteases and their inhibitors such as cystatin C are assumed to play an important role in the pathogenesis of atherosclerosis and coronary heart disease (CHD). The aim of the study was to investigate the impact of cystatin C polymorphisms on cystatin C plasma levels and on prognosis of patients with CHD.

Methods and Results—

Four polymorphisms in the promoter and exon 1 of the cystatin C gene (−82GC, −5GA, +4AC, and +148AG) and cystatin C plasma levels were determined in a cohort of 1013 patients with manifest CHD and aged 30 to 70 years participating in an in-hospital rehabilitation program. Patients were followed-up for a mean of 33.5 months and a combined end point (fatal and nonfatal cardiovascular disease [CVD] events) was used as the outcome variable. The major haplotype −82G/−5G/+4A was associated with cystatin C plasma levels with persons homozygous for the major haplotype having the highest levels (
P
=0.01). However, the haplotype was not associated with fatal and nonfatal cardiovascular events during the 3-year follow-up.

Conclusions—

The major haplotype −82G/−5G/+4A of the cystatin C gene determines plasma levels of cystatin C with homozygous persons having the highest plasma levels, but there was no association with secondary CVD events in this study.
Myocardial Interstitial Matrix Metalloproteinase Activity Is Altered by Mechanical Changes in LV Load
Authors: Deschamps Anne M. , Apple Kimberly A. , Leonardi Amy H. , McLean Julie E. , Yarbrough William M. , Stroud Robert E. , Clark Leslie L. , Sample Jeffrey A. , Spinale Francis G.
Published: April 2005

LV myocardial remodeling is a structural hallmark of hypertensive hypertrophy, but molecular mechanisms driving this process are not well understood. The matrix metalloproteinases (MMPs) can cause myocardial remodeling in chronic disease states, but how MMP activity is altered with a mechanical load remains unknown. The present study quantified interstitial MMP activity after a discrete increase in LV load and dissected out the contributory role of the angiotensin II Type 1 receptor (AT
1
R). Pigs (38kg) were randomized to undergo (1) increased LV load by insertion of an intra-aortic balloon pump (IABP) triggered at systole for 3 hours, then deactivated (n=11); (2) IABP and AT
1
R blockade (AT
1
RB; valsartan, 3 ng/kg/hr; n=6). MMP activity was directly measured in the myocardial interstitium using a validated inline digital fluorogenic microdialysis system. IABP engagement increased LV peak pressure from 92±3 to 113±5 and 123±7 mm Hg in the vehicle and AR
1
RB group, respectively, and remained elevated throughout the IABP period (
P
<0.05). With IABP disengagement, segmental shortening (% change from baseline of 0) remained depressed in the vehicle group (-32.2±11.8%,
P
<0.05) but returned to baseline in the AT
1
RB group (2.3±12.5%). MMP activity decreased with IABP in both groups. At IABP disengagement, a surge in MMP activity occurred in the vehicle group that was abrogated with AT
1
RB (3.03±0.85 versus 0.07±1.55 MMP units/hr,
P
<0.05). A transient increase in LV load caused a cyclic variation in interstitial MMP activity that is regulated in part by the AT
1
R. These temporally dynamic changes in MMP activity likely influence myocardial function and structure with increased LV load.
Cardiac Sarcoplasmic Reticulum Calcium Release and Load Are Enhanced by Subcellular cAMP Elevations in PI3Kγ-Deficient Mice
Authors: Kerfant Benoit-Gilles , Gidrewicz Dominica , Sun Hui , Oudit Gavin Y. , Penninger Josef M. , Backx Peter H.
Published: April 2005

We recently showed that phosphoinositide-3-kinase-γ–deficient (PI3Kγ
−/−
) mice have increased cardiac contractility without changes in heart size compared with control mice (ie, PI3Kγ
+/+
or PI3Kγ
+/−
). In this study, we show that PI3Kγ
−/−
cardiomyocytes have elevated Ca
2+
transient amplitudes with abbreviated decay kinetics compared with control under field-stimulation and voltage-clamp conditions. When Ca
2+
transients were eliminated with high Ca
2+
buffering, L-type Ca
2+
currents (
I
Ca,L
), K
+
currents, and action potential duration (APD) were not different between the groups, whereas, in the presence of Ca
2+
transients, Ca
2+
-dependent phase of
I
Ca,L
inactivation was abbreviated and APD at 90% repolarization was prolonged in PI3Kγ
−/−
mice. Excitation-contraction coupling (ECC) gain, sarcoplasmic reticulum (SR) Ca
2+
load, and SR Ca
2+
release fluxes measured as Ca
2+
spikes, were also increased in PI3Kγ
−/−
cardiomyocytes without detectable changes in Ca
2+
spikes kinetics. The cAMP inhibitor Rp-cAMP eliminated enhanced ECC and SR Ca
2+
load in PI3Kγ
−/−
without effects in control myocytes. On the other hand, the β-adrenergic receptor agonist isoproterenol increased
I
Ca,L
and Ca
2+
transient equally by ≈2-fold in both PI3Kγ
−/−
and PI3Kγ
+/−
cardiomyocytes. Our results establish that PI3Kγ reduces cardiac contractility in a highly compartmentalized manner by inhibiting cAMP-mediated SR Ca
2+
loading without directly affecting other major modulators of ECC, such as AP and
I
Ca,L
.