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Plasma 5-hydroxytryptamine (serotonin), tryptophan, neopterin and cortisol levels were measured in patients with depressive cancer cachexia and in healthy controls during the same time period. Patients with advanced cancers had significantly raised neopterin, a marker of endogenous gamma-interferon (IFN-γ) production, and cortisol values, but decreased serotonin and tryptophan levels. Much work has been done to elucidate the possible role of serotonin in depressive states. IFN-γ induces a high level of indoleamine dioxygenase (IDO), a tryptophan degrading enzyme, and high cortisol levels induce high tryptophan oxygenase activity, which in turn increases metabolism along the tryptophannicotinic acid pathway. These results suggest that persistent immune activation and intense adrenal activity occur in patients with cancer cachexia, resulting in disorders involving tryptophan metabolism followed by depression in cancer cahexia.

Mental retardation is detected in 20-30% of children with epilepsy at hospitals specializing in treatment of childhood epilepsy. However, the incidence of mental deterioration in childhood epilepsy is not high. In this study, mental deterioration was found in 52 (1.8%) of the 2,880 children with epilepsy at Okayama University Hospital. The patients showing mental deterioration mostly suffered from specific epileptic syndromes, such as West syndrome, Lennox-Gastaut syndrome, severe myoclonic epilepsy in infancy and epilepsy with continuous spike-waves during slow wave sleep. These types of epilepsy show generalized electroencephalographic (EEG) abnormalities. It is presumed that mental deterioration is caused by the total effects of prolonged diffuse EEG abnormalities and the age of the patients. Antiepileptic drugs exert a relatively minor effect on mental deterioration.

A simian cell line, Si-IIA, harboring Epstein-Barr-virus (EBV) -related herpesvirus (Si-IIA-EBV), produces malignant lymphoma in rabbits when administered by intravenous inoculation. In this study, we analyzed the Si-IIA-EBV genome and compared it with human EBV and herpesvirus macaca fascicularis 1 (HVMF 1 ), which is associated with B-cell lymphoma developing in SIV-infected immunosuppressed monkeys. DNA from Si-IIA-EBV was amplified by the polymerase chain reaction using three different primer pairs complementary to human EBV (B95-8) DNA; two of the primer pairs covered part of the long internal repeat 1 region (IR 1) and the third covered part of the BRRF 1 region. Direct sequencing of the three PCR products revealed that Si-IIA-EBV DNA had about 82% nucleotide homology to the human EBV DNA in all three regions and 92.4% homology to HVMF1 in the IR1 region. The blotting pattern by Southern blot analysis was different between Si-IIA-EBV and human EBV.

We purified a 44-kDa nuclear protein from salt-extract of permeable mouse ascites sarcoma cells in an effort to isolate factors involved in the repair of acid-depurinated DNA. It was copurified with a major AP endonuclease (APEX nuclease) by sequential column chromatography then further purified by sodium dodecyl sulphate-poly-acrylamide gel electrophoresis as a possible DNA repair support factor. Its partial amino acid sequences were determined, and a cDNA clone for the protein was isolated from a mouse T-cell cDNA library using long degenerate oligonucleotide probes deduced from the amino acid sequence. The complete nucleotide sequence of the cDNA (1.7 kilobases) was determined. Northern hybridization using this cDNA detected two transcripts: 1.8kb being the major one and 2.6 kb being the minor one. The complete amino acid sequence for the protein predicted from the nucleotide sequence of the cDNA indicates that the 44-kDa protein consists of 394 amino acids with a calculated molecular weight of 43,698. In tests performed thus far, the recombinant 44-kDa protein expressed in Escherichia coli has not expressed any repair-support activity. It remains to be analyzed whether the protein attains this activity after appropriate posttranslational modifications. Most parts of the 44-kDa protein cDNA and the deduced amino acid sequence were found to be identical to those of the protein p38 -2G4, recently reported as a cell cycle-specifically modulated nuclear protein of 38kDa. The p38-2G4 may be a truncated form of the present 44-kDa protein.

To evaluate worker's exposure to mixed solvents, equations for the calculation of the biological hazard index, which is defined as biological levels tolerable for exposure to mixture, were developed. When biological levels of exposure indicators were not affected by coexposure, rules similar to those for airborne monitoring could be applied. Namely, when the components had additive effects, the biological hazard index was calculated from the concentration of urinary metabolites or parent solvents, by an equation which was essentially similar to the equation for the calculation of the hazard index. In the present study, the confidence limits of the biological hazard index and predictive limits for individual specimens were calculated. These equations could be used under the condition that the uptake, metabolism and elimination of solvents were practically unaffected by coexposure. When urinary metabolites or solvents of some components of a mixed solvent alone were determined and those of the remaining components were not determined, the concentration of urinary metabolites or solvents of remaining components were estimated from the airborne concentration of the other components.

A new myeloid cell line, MTO-94, was established from the bone marrow of a patient with myelodysplastic syndrome (MDS). MTO-94 cells matured in culture medium without the addition of growth factors, and yielded neutrophils with pseudo-Pelger Huët anomaly or hypersegmentation until 6 months. Ten months after the start of cell cultivation, MTO-94 consisted of myeloblasts. Surface phenotypes were as follows: CD7 90.3%, CD13 99.6%, CD33 75.6%, HLA-DR 96.3% and CD34 0.9%. The karyotype was 46, XY, i(17q). The proliferation of MTO-94 cells was enhanced by rhlL-3, G-CSF, rhGM-CSF and rhSCF but not by rhlL-6 and erythropoietin. MTO-94 cells with i(17q) might be useful in the study of biological aspects of not only MDS, but also hematological malignancies with i(17q) as the sole chromosomal anomaly.

The findings of three-dimensional computed tomography (3DCT) and two-dimensional computed tomography (2DCT) with helical CT scanning were compared for 21 patients with maxillofacial bone fractures. The results of this study suggest that the 3DCT evaluation can be divided into 3 groups. The first group, in which 3DCT is superior to 2DCT, includes severe complicated midface fractures, for example, tripod fractures and complicated maxillary bone fractures. The second group, in which 3DCT is equal to 2DCT, includes simple fractures, for example, nasal bone fractures and isolated zygomatic fractures. In this group, patients and their families could easily understand the nature of the fracture and clinical course shown by 3DCT as compared with conventional X-ray and 2DCT. The third group, in which 3DCT is inferior to 2DCT, includes blowout fractures. Although 3DCT does not provide additional information in blowout fractures, helical scanning permits clear observation of multiplanar images without artifacts arising from metal prostheses by excluding lower slices during image reconstruction. We conclude that 3DCT provides useful information, especially in regard to the extent of complex fracture lines, as in tripod fractures.

We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50%), and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.

The purpose of this study was to investigate the surgical outcomes and to determine indicators of the necessity of surgical intervention. Twelve consecutive patients harboring symptomatic sacral perineural cysts were treated between 1995 and 2003. All patients were assessed for neurological deficits and pain by neurological examination. Magnetic resonance of imaging, computerized tomography, and myelography were performed to detect signs of delayed filling of the cysts. We performed a release of the valve and imbrication of the sacral cysts with laminectomies in 8 cases or recapping laminectomies in 4 cases. After surgery, symptoms improved in 10 (83%) of 12 patients, with an average follow-up of 27 months. Ten patients had sacral perineural cysts with signs of positive filling defect. Two (17%) of 12 patients experienced no significant improvement. In one of these patients, the filling defect was negative. In conclusion, a positive filling defect may become an indicator of good treatment outcomes.

The direct intracellular delivery of proteins has, until recently, been difficult to achieve, due primarily to the bioavailability barrier of the plasma membrane. During the past 15 years, a variety of peptides called protein transduction domains (PTDs) or cell penetrating peptides (CPPs), have been characterized for their ability to translocate into live cells. The most commonly studied are homeodomain transcription factors such as Antennapedia, the herpes simplex virus (HSV) type 1 protein VP22, and the human immunodeficiency virus (HIV-1) transactivator TAT protein. Recently, polyarginine exhibits even greater efficiency in terms of delivery of several peptides and proteins. Numerous examples of biologically active full-length proteins and peptides have been delivered to cells and tissues, both in vitro and in vivo. These studies offer new avenues for treatment of several diseases. The main mechanism of protein transduction is an electrostatic interaction with the plasma membrane, penetration into cells by macropinocytosis, and a release to cytoplasm and nuclei by retrograde transport. Moreover, the intercellular transfer of endogenous transcription factors, such as TAT and homeoproteins, seems to point to an original and important mode of signal transduction. The protein transduction systems have opened up several possibilities, not only for the development of new peptide/protein drugs but also for consideration of their physiological and developmental implications.

We evaluated the plasma homocysteine (tHcy) and nitric oxide metabolites (nitrite plus nitrate; NOx) data of consecutive patients undergoing diagnostic coronary angiography (n=79) with respect to the presence and severity of coronary artery disease (CAD), the presence of acute coronary syndromes (ACS), and the risk status of patients. Hyperhomocysteinemia (>15 micromol/L) was detected in 11% of the controls (n=19) and 37% of CAD patients (n=60) (p=0.03). Plasma tHcy in CAD patients was not significantly different from controls, but those with 3-vessel disease had a significantly higher tHcy concentrations than did controls (p=0.049). The patients with 3-vessel disease and ACS had the highest concentrations of tHcy (16.9 +- 4.4 micromol/L), and the difference from the ACS patients with 1- and 2-vessel involvement was significant (p=0.03). In patients with 1-vessel involvement, tHcy was correlated with NOx (r=0.62, p=0.005); in patients with 2- and 3-vessel disease this correlation could not be observed. The high-risk patients (n=51) had a higher mean number of vessel involvement and tHcy (p<0.001, p<0.05, respectively) but lower NOx (p<0.05) when compared to the low-risk patients (n=28). It appears that in the early stages of atherosclerosis hyperhomocysteinemia causes an increase in NOx production, but with progression of the disease this compensatory increase disappears.

Human esophageal cancers have been shown to express high levels of epidermal growth factor receptor (EGFR) and a relationship between high EGFR expression and local advance, the number of lymph node metastases, life expectancy, and sensitivity to chemo-radiotherapy has been demonstrated. We examined the use of gefitinib, an orally active EGFR-selective tyrosine kinase inhibitor, as a new strategy for treatment of esophageal carcinoma. The effects of gefitinib were evaluated in monotherapy and in combination with radiotherapy in human esophageal carcinoma cell lines. Gefitinib produced a dose-dependent inhibition of cellular proliferation in all of the 8 esophageal carcinoma cell lines examined, with IC50 values ranging from 5.7 microM to 36.9 microM. In combination, gefitinib and radiotherapy showed a synergistic effect in 2 human esophageal carcinoma cell lines and an additive effect in 5 cell lines. Western blotting demonstrated that gefitinib blocked activation of the EGFR-extracellular signal-regulated kinase (Erk) pathway and the EGFR-phosphoinositide-3 kinase (PI3K)-Akt pathway after irradiation. These results suggest that further evaluation of EGFR blockade as a treatment for esophageal cancer should be performed, and that radiotherapy combined with EGFR blockade may enhance the response of esophageal carcinoma to therapy.

The purposes of this study were to examine whether body sway is altered immediately after strabismus surgery in children and to find preoperative clinical factors associated with body sway. In a prospective study, body sway was measured on 1-3 days before surgery and on the third day after surgery; for the measurements, computerized static stabilometry was carried out on 28 consecutive patients with strabismus (age range: 3 to 12 years old; mean: 7.4) who underwent strabismus surgery under general anesthesia. The linear length of the sway path (cm), the linear length of the sway path in a particular unit of time (cm/second), and the area of the sway path (cm2), indicative of the extent of body sway, all increased significantly among a total of 28 patients in both conditions of the patient's eyes open and closed, as well as among those in a subgroup of 16 patients with exotropia, after they had undergone strabismus surgery (p < 0.05, Wilcoxon signed ranks test). The center of pressure along the Y axis of orientation from the toe to the heel was found to deviate significantly toward the heel postoperatively, as compared with the preoperative center in the subgroup of 16 patients with exotropia (p < 0.05). Before surgery, 15 patients with no stereoacuity exhibited a greater amount of body sway when their eyes were open than did 13 patients with measurable stereoacuity (p < 0.05, Mann-Whitney U-test). In the subgroup of 16 patients with exotropia when their eyes open, 3 patients with abnormal head posture exhibited more extensive body sway than did 13 patients without abnormal head posture (p < 0.05). Body sway was found to significantly increase immediately after strabismus surgery in children with strabismus. Stereoacuity and abnormal head posture are 2 clinical factors associated with preoperative postural instability.

We attempted to prepare colloidal iron within tissues by means of microwave irradiation. Mouse tissue blocks were fixed with a mixture of paraformaldehyde and ferric chloride in a cacodylate buffer, immersed in a cacodylate buffered ferric chloride solution, and irradiated in a microwave processor. Colloidal iron was prepared within tissues or cells, and was observed in the form of electron dense fine granules (1-2 nm in diameter) by transmission electron microscopy. Collagen fibrils in the connective tissue showed colloidal iron deposition at regular periodical intervals. Cells in the splenic tissue showed that fine colloidal granules were deposited on the ribosomes but not on the nuclear chromatin. This finding suggests that ferric ions could not diffuse into the nucleus, which was surrounded by the nuclear envelope. The podocyte processes of the renal glomerulus were stained diffusedly. Though this microwave in situ colloidal iron preparation method has some limitations, it is convenient for use in biomedical specimen preparation in transmission electron microscopy.

Previous EEG studies have shown that transcendental meditation (TM) increases frontal and central alpha activity. The present study was aimed at identifying the source of this alpha activity using magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously on eight TM practitioners before, during, and after TM. The magnetic field potentials corresponding to TM-induced alpha activities on EEG recordings were extracted, and we attempted to localize the dipole sources using the multiple signal classification (MUSIC) algorithm, equivalent current dipole source analysis, and the multiple spatio-temporal dipole model. Since the dipoles were mapped to both the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), it is suggested that the mPFC and ACC play an important role in brain activity induced by TM.

To evaluate recent improvements in lung cancer screening, we compared the results of recently conducted lung cancer screening with those of a previous screening. This study compared the survival of lung cancer patients detected by lung cancer screening conducted between 1976 and 1984 (early period) with that conducted between 1989 and 1997 (late period). Two hundred seventy-six patients with lung cancer were detected in the early period and 541 patients with lung cancer were detected in the late period. The median survival time (late : 49.8 vs. early : 27.8 months) and the 5-year survival rate (late : 47.8 vs. early : 34.8%) of the patients with lung cancer detected in the late period were significantly better than those in the early period (p = 0.0054). Among patients undergoing resection, the proportion of pathological stage I patients in the late period was significantly higher than that in the early period (late : 60.8 vs. early : 54.9%, p = 0.005). Multivariate analysis showed that the screening time period was a significant prognostic factor (hazard ratio = 0.685, 95% confidence interval : 0.563-0.832, p = 0.0002). These results were consistent with the findings of case-control studies of lung cancer screening programs in the late period recently conducted in Japan, which also showed a greater efficacy for screening than for previous case-control studies in the early period.

We describe here a patient with a recurrent hemangiopericytoma of the superior mediastinum 23 years after an initial complete resection. In the current biopsy specimen, the tumor cells were much more anaplastic than those seen 23 years ago. Although the patient was treated with chemotherapy, which consisted of ifosfamide and epirubicin, the tumor was unresponsive and he died 6 months later from disease progression. Careful long-term follow-up is mandatory for patients with hemangiopericytomas because recurrence with greater malignancy can develop following an extended disease-free interval.

This study was carried out to determine whether an extracorporeal membrane oxygenation (ECMO) support could be sufficiently conducted by the right ventricle alone from the viewpoint of the hemodynamics and blood gas state. Six infant dogs underwent a bypass between the left pulmonary artery and left atrium with an in-line oxygenator after a left pneumonectomy. Partial ECMO support was conducted simply by opening the circuit, and total ECMO support was conducted by ligating the right pulmonary artery. After the establishment of partial ECMO, approximately one-third of the right ventricular output was passively shunted through the bypass circuit, and the cardiac index and central venous pressure did not change. The mean pulmonary arterial pressures increased significantly. After a complete ligation of the right pulmonary artery, all 6 dogs survived for 12 h, but the cardiac output and blood pressure decreased significantly. The blood gas state was sufficiently maintained throughout the experiment. The results suggest the possibility of using the pumpless ECMO support. However, the flow resistance of the membrane oxygenator proved to still be too high for use in a total pumpless ECMO. Further studies on long-term ECMO and the development of a membrane oxygenator with a considerably low flow-resistance are needed.