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Our group has been developing an Nb-rod-processed CuNb-reinforced Nb3Sn Rutherford cable for developments in high-field superconducting magnets, such as a 25-T cryogen-free superconducting magnet. The Rutherford cable has good mechanical, electrical, and superconducting properties in high fields. In this paper, we investigated the influence of winding coil diameters on the transport properties of the Rutherford cable for the coil application wound with a react-and-wind method. We prepared two Rutherford coils with diameters of 110 mm (0.2% pure bending strain) and 70 mm (0.6% pure bending strain) with 0.7% prebending treatment in order to measure the critical current at various temperatures in fields up to 18 T. We found that the Rutherford coil with a diameter of 110 mm has good transport properties. The critical current of the Rutherford coil with a diameter of 70 mm exhibited a deterioration of about 14% in comparison to the coil having a diameter of 110 mm. Although the tensile strain dependence of the critical current $(I_{c})$ suggests a large deterioration for the 0.6% pure bent coil, the Rutherford coil can keep the high $I_{c}$ under a large pure bending strain.

We have developed a CuNb-reinforced Nb3Sn (CuNb/Nb3Sn) wire. Critical current $(I_{c})$ of prebent CuNb/Nb3Sn coils with various diameters was investigated in order to develop a Nb3Sn superconducting magnet by a react-and-wind (R&W) method. It was found that the prebending treatment enhances $I_{c}$ of the small pure bending coil. In the small pure bending strain region, $I_{c}$ of the prebent coil with over 96-mm outer diameter is larger than that of the as-reacted coil. However, the as-reacted coils exhibited large $I_{c}$ in the large pure bending strain region. Calculated results on the basis of the perfect current transfer model with a neutral axis shift successfully indicated the enhancement behavior of $I_{c}$ by pure bending strains. Hence, we can understand the relationship between coil diameter and prebending treatment for the R&W method using CuNb/Nb3Sn wires.

Nb-rod-method Cu-Nb reinforced Nb3Sn (Cu-Nb/Nb3Sn) wires have been successfully developed for commercialization of the react-and-wind (R&W) processed Nb3Sn coils. Superconducting performance of the Cu-Nb/Nb3Sn wires is improved by applying the prebending treatment at room temperature, because of releasing the residual stress of Nb3Sn filaments (prebending strain effects). The purpose of this study is to confirm the efficient use of the prebending strain effects for optimizing critical current $(I_{c})$ characteristics under pure bending strain on the R&W coil design. The Cu-Nb/Nb3Sn strands of 0.8-mm diameter were heat treated at 670 °C for 96 h on stainless steel grooved cylindrical holders of different radii of 10.1–32.1 mm. After half of the reacted strands were applied repeating prebending strain of ±0.5%, each of the prebent strands and the as-reacted (without prebending) strands was transferred to a Ti-6Al-4V alloy grooved cylindrical holder of 15.6-mm radius. Then, those $I_{c}$ measurements were carried out under applied pure bending strains ranging from −0.9% to +0.84% at 11–17 T, 4.2 K. As a result, the prebent strand showed no deterioration of $I_{c}$ in the applied pure bending strain ranging from −0.5% to +0.5% and had larger $I_{c}$ than that of the as-reacted strand at no pure bending strain. In this paper, the $I_{c}$ enhancements of the prebent Cu-Nb/Nb3Sn strands under pure bending strains are analyzed by using the $I_{c}$ characteristics under axial strains.

We developed Cu-Nb reinforced Nb 3 Sn Rutherford cables for wide-bore high magnetic field coils that were able to be produced by React-and-Wind technique. The Cu-Nb/Nb 3 Sn strands were reinforced by internal Cu-20 vol%Nb composites fabricated by the Nb-rod-method and were manufactured through the bronze-process. The Rutherford cables composed of sixteen un-reacted Cu-Nb/Nb 3 Sn strands of 0.8-mm diameter were heat-treated at 670 °C for 96 hours. After that, repeated bending strains (pre-bending strains) were applied to the flatwise direction of the reacted Nb 3 Sn Rutherford cables at room temperature. Critical current (Ic) values of Cu-Nb/Nb 3 Sn strands extracted from the Rutherford cables were compared to those of the single strands that had undergone the same processing as the cables. I c values under the applied tensile stress of the Rutherford cable were increased by the pre-bending treatment as similar to the single strand. The performances of Cu-Nb/Nb 3 Sn Rutherford cables were improved by utilization of the pre-bending process.

We are planning to develop three large superconducting magnets, using CuNb-reinforced Nb3Sn Rutherford cables with the prebending treatment. CuNb-reinforced Nb3Sn wires using a new Nb-rod-processed CuNb composite were developed for the Rutherford cables. In this study, the prebending effects for the mechanical and the superconducting properties of the Nb-rod-processed CuNb/Nb3Sn wire were investigated. We found that the CuNb/Nb3Sn wire with 0.8% prebending treatment had largely enhanced critical current at 4.2 K. The reduction of the n-value was observed around 0.8% prebending strain. The mechanical properties of the prebent wires were enhanced. Young's modulus and 0.2% proof stress of the wire with prebending treatment at 4.2 K are 180 GPa and 270 MPa, respectively. The residual strain was released from 0.30% to 0.15% by 0.8% prebending treatment.

A 7-strand Nb3Sn superconducting cable, which consists of three pre-bent CuNb/Nb3Sn strands, three stainless-steel (SS) strands, and a center SS strand, was fabricated. 2.5 turns of the cable was wound on a 262-mm diameter GFRP bobbin A triplet consisting of three pre-bent CuNb/Nb3Sn strands was also tested for comparison. The reinforcement effect of stainless-steel strands in a cable was investigated to develop a high-strength large-current superconducting cable. The hoop stress test result indicated that the stainless-steel reinforced CuNb/Nb3Sn cable showed better performance than the CuNb/Nb3Sn triplet under the hoop stress, because the stainless-steel strands reduced the hoop stress on Nb3Sn strands. Furthermore, the solder impregnation of the cable, which made the seven strands a monolithic conductor, improved its performance.

An application of the prebending effect to a cabling process using Nb3Sn strands was demonstrated. The prebending effect is the enhancement effect of superconducting properties due to the repeated prebending treatment for practical bronze-route Nb3Sn wires. CuNb/Nb3Sn and Cu/Nb3Sn strands were applied prebending treatment using 10 fixed pulleys with 0.8% prebending strain. Four kinds of triplets, i.e., prebent CuNb/Nb3Sn, no-prebent CuNb/Nb3Sn, prebent Cu/Nb3Sn and no-prebent Cu/Nb3Sn triplets were fabricated. Critical currents were measured for the four kinds of triplets in magnetic fields up to 11 T at 4.2 K. The obvious critical current enhancement due to the prebending effect was maintained for the prebent CuNb/Nb3Sn triplet. The results imply that the prebending treatment for high-strength Nb3Sn strands is applicable to the cable conductor fabrication.

TEPCO and Furukawa have been developing a compact 66 kV-class high- T c superconducting (HTS) cable that employs two new important technologies. One technology reduces AC losses of HTS cable. In our studies, we found that using twisted filaments in the HTS tapes in the multi-layer conductor and adjusting winding pitches of layers dramatically reduces AC losses. Another technology is related to the mass production of HTS cable. To facilitate mass production, we improved the cable design. A three-phase prototype HTS cable was then successfully fabricated with machines at Furukawa Electric. The results of the performance testing of the cable demonstrated that the proposed design and the production method were appropriate.

A patient with primary non-Hodgkin's (B-cell type) lymphoma of the kidney developed hypercalcemia at the terminal stage of the disease. Although the plasma parathyroid hormone level was low, urinary cyclic AMP excretion was elevated. Serum osteocalcin (BGP) was suppressed and the plasma level of 1,25(OH)2D was within the normal range. Serum concentrations of PTH-related protein (PTHrP)-like immunoreactivity (PRP-LI) were elevated, and the tissue concentration of PRP-LI in the postmortem lymph node showed high level along with elevated serum PRP-LI, furthermore the production of PTHrP by the tumor was demonstrated by immunohistochemistry and Northern blotting analysis. These findings indicate that the hypercalcemia of the patient was caused by the PTHrP-producing B-cell lymphoma. Hypercalcemia was restored to normocalcemia by bisphosphonate treatment. Our case will add further information on humoral hypercalcemia in B-cell lymphoma, which rarely has been demonstrated to produce PTHrP.

A Rutherford flat cable that is applicable for operational currents up to 1000 A at 13–14 T was developed using a bronze-processed high-strength Nb3Sn strand with CuNb reinforcement (CuNb/Nb3Sn). The critical current for a 0.8-mm diameter CuNb/Nb3Sn strand is 98 A at 14 T and 4.2 K in the residual strain state. A test coil using the CuNb/Nb3Sn Rutherford flat cable composed of 16 CuNb-reinforced Nb3Sn strands was fabricated. We measured the critical current properties of the Rutherford test coil and obtained an excellent critical current of 1840 A at 14 T and 4.2 K. By using the strain gauges attached onto the stainless-steel reinforcement tape that was co-wounded with the Rutherford flat cable, it was found that a 300-MPa hoop stress at 4.2 K was applied to the CuNb/Nb3Sn strand. This implies that the critical current for a CuNb/Nb3Sn strand is enhanced to be 115 A at 14 T and 4.2 K through the stress-strain effect of the critical current at 300 MPa.

Stereotactic surgery for Parkinson's disease can be performed using different neuroimaging methods. Ventriculography has been used to locate the coordinates of the structures close to the third ventricle. Although it has several potential disadvantages related to the intraventricular injection of iodine contrast, it is considered a precise method. Computed tomography and magnetic resonance imaging have been used in some centers. In order to compare their efficacy, 50 stereotactic thalamotomies for Parkinson's disease were performed using either ventriculography (VE) (25) or magnetic resonance imaging (MRI) (25). In 14 out of 25 VE procedures, computed tomography (CT-scan) was also used and showed a significant mean difference of coordinate Y and Z. The clinical results employing either VE or MRI were similar, with 80% abolition of tremor in the VE group, and 84% in the MRI group, after a follow up period of at least 3 months. Another 12% of VE and 16% of MRI group showed significant improvement of tremor. Complication rate was 4% in both groups. MRI-guided stereotactic thalamotomy in Parkinson's disease has shown good clinical results, comparable to VE-guided stereotaxis. A cirurgia estereotáxica para doença de Parkinson (DP) pode ser realizada com diferentes métodos de neuroimagem. A ventriculografia (VE) tem sido empregada para determinar as coordenadas estereotáxicas das estruturas próximas ao terceiro ventrículo. Apesar de várias desvantagens relacionadas com a injeção intraventricular de contraste iodado, é considerada como uma técnica precisa. A tomografia computadorizada (TC) e a ressonância magnética (RM) têm sido utilizadas em alguns centros. Para comparar a eficácia dos diferentes métodos, 50 talamotomias estereotáxicas para DP foram realizadas utilizando VE (25 casos) e RM (25 casos). Em 14, dos 25 casos com VE, o emprego concomitante de TC demonstrou diferença média importante nas coordenadas Y e Z. Os resultados clínicos utilizando-se VE ou RM foram similares, com 80% de abolição de tremor no grupo com VE e 84% com RM durante seguimento mínimo de 3 meses. Além disso, 12% do grupo com VE e 16% do grupo com RM apresentaram significativa melhora do tremor. índice de 4% de complicações foi encontrado em ambos os grupos. Não houve mortalidade. A talamotomia estereotáxica guiada por RM para DP demonstrou resultados comparáveis aos obtidos com VE.

The heterosexual transmission of hepatitis C virus (HCV) remains controversial, and data from general populations are scanty. In this cross-sectional study, we assessed the seroprevalence of antibodies to hepatitis C virus (anti-HCV) and the presence and genotype of HCV-RNA among 109 married couples within an endemic, community-based Japanese population. Overall, 25% of the husbands and 32% of the wives had anti-HCV. Spouses with anti-HCV-positive partners were around 2 times more likely to have anti-HCV than spouses with anti-HCV-negative partners (p = 0.01). Of 6 couples in which both spouses had HCV-RNA, however, 3 presented discordant HCV genotypes (type 1b vs. 2b). The couples' anti-HCV concordance status was not significantly influenced by the presence or absence of HCV-RNA among anti-HCV-positive partners (odds ratio [OR]: 0.8 for wives, 0.6 for husbands), nor by the length of marriage, the number of pregnancies or the use of contraceptives. No significant associations with anti-HCV were observed for serum markers of sexually transmitted agents, including human T-lymphotropic virus (OR = 1.1, 95% confidence interval [CI] 0.5-2.3), Treponema pallidum (OR = 0.7; CI 0.1-6.1) and hepatitis B virus (OR = 1.6; CI 0.9-3.0). Our results suggest that the clustering of HCV infection among specific couples within this endemic population may not be attributable to heterosexual transmission. Follow-up studies are necessary to determine the risk of heterosexual transmission of HCV in endemic areas.

Os autores apresentam série 50 pacientes submetidos a cirurgia estereotáctica para processos expansivos intracranianos. Em 12 casos realizou-se um procedimento terapêutico: ressecção tumoral guiada em 5 pacientes e aspiração do conteúdo da lesão nos outros 7. Neste estudo confirmam-se a grande precisão e a baixa morbidade relacionadas com as técnicas estereotácticas. A tomografia computadorizada e a ressonância magnética determinam com acurácia as coordenadas estereotácticas, mas em certos casos a estereo-angiografia cerebral deve ser realizada. As ressecções tumorais guiadas por estereotaxia permitem o tratamento de lesões cerebrais profundas ou em áreas funcionais anteriormente consideradas como inoperáveis. A literatura pertinente é discutida.

The efficacy and safety of oral placebo or odanacatib 10, 25, or 50 mg once weekly for 52 weeks were evaluated in a double-blind, randomized, multi-center study in Japanese female and male patients with osteoporosis.Odanacatib is a selective and reversible cathepsin K inhibitor that decreases bone resorption and increases bone mineral density (BMD).The primary efficacy endpoint was percent change from baseline to week 52 in lumbar spine BMD. Secondary endpoints included percent change in total hip, femoral neck, and trochanter BMD and in bone biomarkers after treatment for 52 weeks.In this study, 286 patients [94% female, mean age (SD) 68.2 (7.1) years] were included in the analysis. The least-squares mean percent changes from baseline to week 52 in the groups receiving placebo, 10, 25 and 50 mg of odanacatib for lumbar spine (L1~L4) BMD were 0.5, 4.1, 5.7, and 5.9% and for total hip BMD were -0.4, 1.3, 1.8, and 2.7%, respectively. The changes in femoral neck and trochanter BMD were similar to those at the total hip. Bone turnover markers were reduced in a dose-dependent manner. However, the effects of odanacatib on bone formation markers were less compared with the effects on bone resorption markers. Tolerability and safety profiles were similar among all treatment groups with no dose-related trends in any adverse events.Weekly odanacatib treatment for 52 weeks increased BMD at the lumbar spine and at all hip sites in a dose-dependent manner and was well tolerated in Japanese patients with osteoporosis.

The repeated prebending treatment for Nb3Sn wires with CuNb reinforcing stabilizer (CuNb/Nb3Sn) largely enhances the critical current. Since the employment of the highstrength CuNb/Nb3Sn wire is very effective for a react-and-wind process Nb3Sn superconducting magnet, we focus on the application of this prebending effect to the reactand-wind process of high-strength strand cables. The Rutherford flat cables composed of sixteen CuNb/Nb3Sn strands were fabricated to be applicable to the react-and-wind method. High-strength CuNb/Nb3Sn strand cables will exhibit the critical current of Ic = 1890 A at 13 T and 4.2 K. In order to construct a compact hybrid magnet, a 20 T-440 mm room temperature bore superconducting magnet consisting of YBCO, CuNb/Nb3Sn, and NbTi section coils is designed, using such Rutherford flat cables in pool-boiling liquid helium.

Biologic effect of human hepatocyte growth factor (hHGF), which is now known to be the same protein of scatter factor and tumor cytotoxic factor, on gastric cancer cell lines were examined. hHGF messenger RNA expression was undetectable in human gastric cancer cell lines TMK-1 (poorly differentiated adenocarcinoma) and MKN-28 (well differentiated adenocarcinoma). Human fetal lung fibroblast cell line MRC-5 and human stomach derived fibroblast ST-Fib expressed high levels of hHGF mRNA. hHGF production was also confirmed in the culture media of the fibroblast cell lines by enzyme linked immunosorbent assay. Interestingly, TMK-1, having weak expression of E-cadherin, showed marked scattering on 0.1% collagen gel with hHGF (10 ng/ml). The same scattering activity was also observed with fibroblast conditioned medium or with stomach derived fibroblast ST-Fib co-culture. Contrarily, well differentiated adenocarcinoma cell line MKN-28 maintaining strong E-cadherin expression did not show this morphologic change. The expression of c-met proto-oncogene, which encodes the receptor for hHGF, and the biochemical character of hHGF receptor did not differ significantly between TMK-1 and MKN-28. On the other hand, Western blot analysis using specific antibody to phosphotyrosine revealed a difference in phosphoprotein pattern between the two cell lines. These results indicate that hHGF produced by the stromal fibroblasts has a histologic type-specific morphogenic activity on gastric cancer cells with different expression of E-cadherin in a paracrine manner in vivo and a different post-receptor signal transduction mechanism.

The aim of the study was to assess the efficacy/safety of once- (100 mg q.d.) or twice-daily (50 mg b.i.d.) sitagliptin 100 mg/day in Japanese patients with type 2 diabetes (T2DM). In this randomized, double-blind study, 80 patients with inadequate glycemic control (HbA1c=6.5-10%; FPG

Full-length cDNA clones for succinyltransferase of the rat alpha-ketoglutarate dehydrogenase complex were isolated from rat heart cDNA libraries in lambda gt11. The cDNA clones were identified as those for rat succinyltransferase by the identity of their predicted amino acid sequence with the NH2-terminal amino acid sequence of rat succinyltransferase determined by protein chemical analysis and the known amino acid sequence of bovine succinyltransferase. The clone with the longest cDNA consisted of 2747 base pairs and coded for a leader peptide of 56 amino acid residues and a mature protein of 386 amino acid residues. The primary structure of rat succinyltransferase showed close similarity to Escherichia coli and Azotobacter vinelandii succinyltransferases, in the COOH-terminal part forming the lipoyl-binding domain and the NH2-terminal part forming the inner core-catalytic domain. However, the rat succinyltransferase did not contain a sequence motif that has been found as an E3- and/or E1-binding site in the dihydrolipoamide acyltransferases of three alpha-ketoacid dehydrogenase complexes (Hummel, K. B., Litwer, S., Bradford, A. P., Aitken, A., Danner, D. J., and Yeaman, S. J. (1988) J. Biol. Chem. 263, 6165-6168, Reed, L. J., and Hackert, M. L. (1990) J. Biol. Chem. 265, 8971-8974). The absence of this sequence was confirmed by direct sequencing of the polymerase chain reaction product of rat heart mRNA and by computer analysis. These results show that the rat succinyltransferase does not have the sequence motif of the putative E3- and/or E1-binding site.

This paper presents a double-gated Spindt-type field emitter with thick extraction gate electrode. Simulation of the dependence of the electric field at the top of the emitter tip on the thickness of the extraction gate electrode is done. This emitter is fabricated using a silicon-on-insulator wafer as a starting material. The current-voltage characteristics show that emission current is obtained at an extraction gate voltage of about 66 V

We analyzed the cranial computerized tomography scans (CT) of 1000 consecutive patients with the history of seizures. The seizures were classified in generalized tonic-clonic seizures (GS) and partial seizures (PS) on the basis of the clinical semiology, as it was described by the patients and family members. Seizure types were correlated with age group, sex and CT findings. GS were observed in 70.7% of the patients and PS in 29.3 %. An increased incidence of GS was noted among the age groups 0 to 10 yrs (31%) and 11 to 20 yrs (21.8%). For PS the 0 to 10 yrs (24.5 %), 21 to 30 yrs (16.7%) and 31 tp 40 yrs (18.5%) age groups were the most prevalent groups. The CT scan findings for the GS group were the following: normal studies 48.8 % of the patients, calcifications/cysticercosis (14.0%), neurocysticercosis/cysts (9.6 %), hydrocephalus (4.3%), ischemia (4.2 %), non-definite lesions (4.1 %), tumor (2.5%), and others (12.5%). In the PS group we found 37.4% of normal studies, calcifications/cysticercosis (11.2%), neurocysticercosis/cysts (12.2%), tumor (10.5%), ischemia (5.4%), hydrocephalus (3.7%), non-definite lesions (8.1%) and others (11.6%). We emphasize the importance of CT scan imaging in patients presenting with seizures, particularly in the diagnosis of cysticercosis.

Analizamos retrospectivamente as tomografias computadorizadas (TC) de crânio de 1000 pacientes consecutivos, com história clínica de crises epilépticas classificadas do ponto de vista clínico em generalizadas (CG) e parciais (CP). Nossos resultados mostraram a presença de CG em 70,7% dos pacientes, sendo 57,1% do sexo masculino e 42,9% do sexo feminino e, CP em 29,3%, sendo 60,0% do sexo maculino e 40,0% do sexo femninino. As faixas etárias de maior incidência foram entre 0 a 10 (31,0%) e 11 a 20 (21,8%) anos nos pacientes com CG e 0 a 10 (24,5%), 21 a 30 (16,7%) e 31 a 40 anos (18,4%) nos pacientes com CP. Os resultados tomográficos no grupo com CG foram: normais (48,8%) e alterados em 51,2%, sendo esses achados definidos como calcificações/cisticercose (14,0%), neurocisticercose/cistos (9,6%) hidrocefalia (4,4%), infarto (4,2%), indefinido (4,0%), tumor (2,5%) entre outros (12,5,%). Nos pacientes com CP os exames tomográficos foram normais em 37,4%, alterados em 62,7%, tendo os diagnósticos de neurocisticercose/cistos (12,2%), calcificações/cisticercose (11,2%), tumor (10,5%), indefinido (8,1%), infarto (5,4%), hidrocefalia (3,7%) e outros (11,6%). Salientamos a importância da TC em pacientes com epilepsia, particularmente para o diagnóstico de neurocisticercose. We analized the cranial computorized tomography scans (CT) of 1000 consecutive patients with the history of seizures. The seizures were classified in generalized tonic-clonic seizures (GS) and partial seizures (PS) on the basis of the clinical semiology, as it was described by the patients and family members. Seizure types were correlated with age group, sex and CT findings. GS were observed in 70.7% of the patients and PS in 29.3 %. An increased incidence of GS was noted among the age groups 0 to 10 yrs (31%) and 11 to 20 yrs (21.8%). For PS the 0 to 10 yrs (24.5 %), 21 to 30 yrs (16.7%) and 31 tp 40 yrs (18.5%) age groups were the most prevalent groups. The CT scan findings for the GS group were the following: normal studies 48.8 % of the patients, calcifications/cysticercosis (14.0%), neurocysticercosis/cysts (9.6 %), hydrocephalus (4.3%), ischemia (4.2 %), non-definite lesions (4.1 %), tumor (2.5%), and others (12.5%). In the PS group we found 37.4% of normal studies, calcifications/cysticercosis (11.2%), neurocysticercosis/cysts (12.2%), tumor (10.5%), ischemia (5.4%), hydrocephalus (3.7%), non-definite lesions (8.1%) and others (11.6%). We emphasize the importance of CT scan imaging in patients presenting with seizures, particularly in the diagnosis of cysticercosis.

A 71-year-old woman was admitted for further examination of an increased serum LDH level. Abdominal ultrasonography and CT scan showed a large tumor in her spleen. Because malignant lymphoma was suspected, the spleen was removed for diagnosis and treatment planning. The histopathological and immunohistochemical features of the tumor indicated diffuse large B-cell lymphoma (DLBL). The flow-cytometric immunophenotype of the lymphoma cells was CD2-, CD3-, CD4-, CD5-, CD8+, CD10+, CD19+, CD20+, CD23-, kappa+, lambda-, CD25+, and CD56-. From these findings, the patient was diagnosed as having CD8+ DLBL. To our knowledge, this is the first reported case of primary splenic CD8-positive DLBL.

Cyclin D1, one of the G(1) cyclins, is frequently overexpressed in several types of carcinomas and is thought to play an important role in tumorigenesis and tumor progression including hepatocellular carcinoma. We constructed a retrovirus vector-carrying rat cyclin D1 cDNA in the reverse orientation, resulting in expression of antisense (AS) cyclin D1 mRNA. For efficient transduction of this recombinant retrovirus, two-step gene transfer was performed. The rat hepatoma cell line (dRLh84) was infected with this recombinant retrovirus after preinfection with adenovirus expressing the retrovirus receptor. In the rat hepatoma cells, AS cyclin D1 mRNA was expressed, inducing a decrease in the expression of endogenous cyclin D1 mRNA and an inhibition of cell growth. Moreover, two-step gene transfer of AS cyclin D1 into s.c. hepatoma xenografts resulted in inhibition of tumor growth and prolonged animal survival. In the virus-infected tumor xenografts, expression of cyclin D1 was immunohistochemically inhibited, and apoptosis of hepatoma cells was detected. These findings suggest that transduction of AS cyclin D1 is useful as an adjunct to standard treatments for hepatocellular carcinoma.

Surgical treatment of pancreatic adenocarcinoma has failed to produce many cures secondary to high rates of intraperitoneal relapses and liver metastases. The aim of this ex vivo study was to evaluate the inherent chemosensitivity, radiosensitivity and hyperthermic sensitivity of pancreatic adenocarcinoma and to investigate the usefulness of a 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay utilized in each sensitivity test.Nine human pancreatic adenocarcinomas were tested ex vivo after growth in nude mice. After 72 hr of chemotherapy, radiotherapy and hyperthermia, efficacy was assessed using MTT assay to determine the ratio of surviving fraction of treated cells-to-that of untreated control cells (TIC ratio).Tumor sensitivities as measured by the IC50 (drug concentration producing 50% growth inhibition) varied largely between drugs, ranging larger than 3 x 10(5) ng/mL for 5-FU, larger than 1.5 x 10(2) ng/mL for MMC, 20 ng/mL to 1.4 x 10(3) ng/mL for ADM, and 80 ng/mL to 2.4 x 10(3) ng/mL for CDDP. D0 (dose of radiation reducing the surviving fraction to 37%) ranged from 3.2 to 8.3 Gy (mean +/- standard deviation; 5.8 +/- 1.6 Gy). For hyperthermia, the mean T50 (duration of hyperthermia reducing the surviving fraction to 50%) at 43 degrees C was 9.4 +/- 3.3 min 4.8 to 14.2 min). The T/C ratio at 43 degrees C for 12 min was less than that at 41 degrees C for 30 min (p = .01; the Wilcoxon signed-ranks test). No clear relationship among chemosensitivity, radiosensitivity, hyperthermic sensitivity and pathologic features could be established.Nine human pancreatic adenocarcinomas varied widely in their sensitivity to chemotherapies, especially for 5-FU. These results suggested that MTT assay may be useful in excluding some less sensitive cases of pancreatic cancer. For hyperthermia, sufficient therapeutic time and temperature may realize enough effect against pancreatic adenocarcinoma.

We previously reported that the retroviral vector expressing the herpes simplex virus-thymidine kinase gene under the control of 0.3-kb human alpha-fetoprotein (AFP) gene promoter (AF0.3) provided the cytotoxicity to ganciclovir (GCV) in high-AFP-producing human hepatoma cells but not in low-AFP-producing cells. Therefore, specific enhancement of AFP promoter activity is likely to be required to induce enough cytotoxicity in low-AFP-producing hepatoma cells. In this study, we constructed a hybrid promoter, [HRE]AF, in which a 0.4-kb fragment of human vascular endothelial growth factor 5'-flanking sequences containing hypoxia-responsive element (HRE) was fused to AF0.3 promoter. By means of the reporter gene transfection assay, hypoxia-inducible transcriptions that were mediated by [HRE]AF promoter were detected in low- and non-AFP-producing human hepatoma cells, but not in nonhepatoma cells. When the herpes simplex virus-thymidine kinase gene controlled by [HRE]AF promoter was transduced into hepatoma and nonhepatoma cells by a retroviral vector, the exposure to 1% O2 induced GCV cytotoxicity specifically in the hepatoma cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors consisting of the virus-infected hepatoma cells gradually disappeared by GCV administration. These results indicate that the hypoxia-inducible enhancer of the human vascular endothelial growth factor gene, which is directly linked to human AFP promoter, involves selective and enhanced tumoricidal activity in gene therapy for hepatocellular carcinoma.

Signal transductions induced by growth factors, such as hepatocyte growth factor (HGF) and epidermal growth factor (EGF), and the growth inhibitory factor such as transforming growth factor-β (TGFβ), have been successfully identified as being transduced to cell cycle molecules such as cyclin and cyclin-dependent kinase. Signal transduction in hepatocytes cultured with several growth-stimulatory and growth-inhibitory factors remains unclear. In addition, transcriptional factors regulating cyclin D1 gene expression, which are induced by growth factors, were not identified. In this study, we found that both HGF and EGF additively enhanced mitogen-activated protein kinase (MAPK) activity, and cyclin D1 and cyclin E gene expression resulted in increases in DNA synthesis in primary cultured rat hepatocytes with an additive manner. We also found that TGFβ1 inhibited cyclin E gene expression with no effect on HGF- and/or EGF-induced MAPK activity and cyclin Dl gene expression, resulting in complete inhibition of HGF- and/or EGF-induced DNA synthesis. We isolated the rat cyclin D1 genome containing -5kb 5’-flanking region and found two possible regions responsible for transcriptional factors in the cyclin D1 promoter.

A 29-year-old woman experienced Raynaud's phenomenon, swelling of her fingers, eruptions on her face, and muscle weakness in 1990. She was diagnosed as having mixed connective tissue disease (MCTD) and was treated with prednisolone (PSL) for 3 years. Most of her complaints disappeared after the treatment. In March 1997, she experienced fever, erythema, and lymphadenopathy. Although she was treated with PSL (20 mg/day) again, muscle weakness, mental disturbance, and recto-urinary disturbance appeared. When she was re-admitted to our hospital, increased levels of muscle-derived enzymes and positivity of anti-RNP antibody were found. High signal areas in her cerebrum were shown by magnetic resonance imaging, and slow and spike pattern was shown by electroencephalography. Hypoperfusion of the cerebral blood flow was suggested on single photon emission computed tomography. The number of mononuclear cells, amount of protein and level of interleukin-6 were found to be elevated in her cerebrospinal fluid (CSF). Her neurological manifestations were diagnosed as being due to MCTD, and showed characteristics similar to those of systemic lupus erythematosus. She was treated with PSL (60 mg/day) followed by steroid pulse therapy. Because the response to this treatment was partial, oral administration of cyclophosphamide (CPM) (100 mg/day) was added. Muscle weakness and neurological abnormalities as well as abnormal laboratory findings gradually improved over the following two months. We conclude that the treatment with CPM combined with PSL may be useful, when neurological manifestations of MCTD are serious and resistant to conventional therapy.

We report a case of copper deficiency with anemia and neutropenia due to dumping syndrome after total gastrectomy. Parenteral nutrition containing cupric sulfate promptly improved the dumping syndrome, anemia and neutropenia. This case suggests that total gastrectomy with dumping syndrome can cause copper deficiency, and that copper deficiency should be considered when encountering similar patients with severe anemia and neutropenia.

We report the use of laryngeal mask airway (LMA) to facilitate smooth emergence from anesthesia in 3 patients who underwent lung volume reduction surgery (LVRS) for severely symptomatic emphysema. To prevent coughing during emergence we replaced the endotracheal tube with LMA while patient was still in deep anesthesia. Emergence was smooth without coughing in all three patients, and ventilation with facemask was not needed after removal of LMA. We believe this technique is safe and beneficial for anesthetic management of LVRS.

Visceral larva migrans (VLM) is a disease usually observed in children in which the larvae of animal parasites invade and reside in human tissues for long periods. Although the common causal species of VLM are Toxocara canis and T. cati, we identified three adult patients with VLM, probably due to Ascaris suum, whose diagnosis was made by specific immunoserological tests. The patients complained of respiratory symptoms, and laboratory tests showed pronounced eosinophilia, but neither larvae nor eggs were detected in stool samples. We present the findings of various imaging studies of the patients. Multiple small hypoechoic mass lesions were demonstrated by ultrasound tomography, which disappeared after anti-helminthic therapy. Hepatic mass lesions were detected as low-density areas on computed tomography, as high signal intensities on T2-weighted magnetic resonance images, as space-occupying regions in liver scintigraphy, and as yellow-white nodules in laparoscopy. Although biopsied liver tissue specimens showed marked infiltrations of eosinophiles in the portal tracts and hepatic sinusoids, neither larvae nor eggs could be identified.

We a case of chronic Aspergillus sp. meningitis in a healthy 43-year-old woman successfully treated with fluconazole given orally (300 ms/day). The diagnosis was made by detection of anti-aspergillus antibodies and positive culture to Aspergillus sp. in the cerebrospinal fluid.

Human T-lymphotropic virus type I (HTLV-I) carriers often have abnormal lymphocytes (Ably) that resemble malignant cells of adult T-cell leukemia (ATL). To identify predictors of the level of Ably in a longitudinal study of asymptomatic HTLV-I carriers, we analyzed data from 215 subjects (67 men and 148 women) with multiple Ably measurements on blood smears. Ably+ (those having Ably0.6% of leukocytes counted on a blood smear at least once) was strongly associated with a high proviral load (OR 8.9; 95% CI 4.1, 19.5). The association among those defined as Ably++ (Ably0.6% at all screens or Ably1.6% at least once) was higher (19.7; 6.9, 56.1). Ably++ was also significantly associated with male gender (2.8; 1.0, 7.8). Multivariate analysis of Ably level indicates that men with a high proviral load, high anti-HTLV-I titer and low anti-Tax reactivity have the highest Ably level.

Clonal proliferation of human T-lymphotropic virus type I (HTLV-I)-infected cells has been detected by Southern blot analysis and inverse PCR in patients with adult T-cell leukemia, patients with HTLV-I-associated diseases, and even in asymptomatic carriers. Combining inverse PCR with long PCR, we amplified the genomic DNA regions flanking the integration sites of the HTLV-I provirus to detect clones of infected cells. Inverse long PCR revealed that increased virus load was associated with an increase of both the number of cells in each clone and the number of clones. Clonal proliferations were found in both CD4- and CD8-positive cells in a carrier and a patient with HTLV-I-associated neuropathy/tropical spastic paraparesis. These HTLV-I-infected clones persisted over several years in the same carriers, and, moreover, most of the persistent clones were CD4 positive in a HTLV-I carrier. These findings indicate that HTLV-I infection plays an important role in the clonal expansion of lymphocytes and the prolonged survival of CD4-positive cells in vivo. Surviving T-lymphocytes may be susceptible to genetic changes, leading to the onset of leukemia.

In the surgical management of skull base lesions and vascular diseases such as giant aneurysms, involvement of the internal carotid artery may require the resection or the occlusion of the vessel. The anastomosis of the external carotid artery and the middle cerebral artery with venous graft may be indicated to re-establish the blood flow. To determine the best suture site in the middle cerebral artery, an anatomical study was carried out. Fourteen cerebral hemispheres were analysed after the injection of red latex into the internal carotid artery. The superior and inferior trunk of the main division of the middle cerebral artery have more than 2 mm of diameter. They are superficial allowing an anastomosis using a venous graft. The superior trunk has a disadvantage, it gives rise to branches for the precentral and post-central giri. The anastomosis with the inferior trunk presents lower risk of neurological deficit even though the angular artery originates from it. No tratamento cirúrgico das lesões da base do crânio e patologias vasculares como aneurismas gigantes, a ressecção ou oclusão da artéria carótida interna pode ser necessária. A anastomose das artérias carótida externa e cerebral média com interposição de enxerto venoso pode ser utilizada para restabelecer o fluxo sangüíneo. Para determinar o melhor local de sutura na artéria cerebral média, realizou-se um estudo anatômico. Quatorze hemisférios cerebrais foram analisados depois da injeção de látex vermelho na artéria carótida interna. Os ramos superior e inferior da divisão principal da artéria cerebral média têm mais de 2 mm de diâmetro. Eles são superficiais e permitem uma anastomose utilizando um enxerto venoso. O tronco superior tem a desvantagem de dar origem aos ramos para os giros pré e pós-centrais. A anastomose com o tronca inferior apresenta menor risco de déficit neurológico, apesar da artéria angular ter origem desse vaso.

A 64-year-old woman with a solitary mass (18 mm in diameter) of hepatocellular carcinoma underwent hepatic arterial infusion therapy with water-in-oil-in-water emulsion (W/O/W) prepared by the membrane emulsification technique using a controlled pore glass membrane. In the W/O/W, numerous microdroplets of iodized poppy-seed oil (IPSO), which contained many vesicles of aqueous solution of epirubicin, were suspended in the external aqueous phase. The mean diameter of the IPSO microdroplets was 30 microns. Seventeen milliliters of the W/O/W containing 40 mg of epirubicin and 5 ml of IPSO was infused into the proper hepatic artery. No severe side effects were encountered. Computed tomography taken 3 days after the treatment revealed a clearly defined deposition of IPSO within the tumor. Serum alpha-fetoprotein levels, 5.35x10(3) ng/ml, before treatment, decreased to 131 ng/ml on 38 days after treatment. The tumor was extirpated and histopathological examination revealed complete necrosis of the tumor.

Human hepatocyte growth factor (hHGF), now known to be identical with scatter factor and tumor cytotoxic factor, is thought to be involved in the regeneration of the liver in humans.We measured the levels of immunoreactive hHGF levels in peritoneal fluid before and after partial hepatectomy in 37 patients, 10 with and 27 without cirrhosis. The presence of hHGF was confirmed in human peritoneal fluid with rat hepatocytes in primary culture and Western blot.Levels of hHGF increased significantly in peritoneal fluid after surgery, with its total concentration being correlated with the weight of resected liver 168 hours postoperatively.Findings suggest that the hHGF levels in peritoneal fluid may indicate the extent of hepatic damage following partial hepatectomy and other liver diseases.