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BackgroundEmerging evidence suggests that fish consumption may have beneficial effects on mood disorders. However, no study has been reported on this issue in young adults to date. The aim of this study was to investigate the relationship between fish consumption and depressive symptoms in Japanese undergraduate students.MethodsThe 20-item Center for Epidemiologic Studies Depression Scale was used to measure depressive symptoms with a cut-off score of 16. A total of 4190 completed questionnaires (from 2124 men and 2066 women) were received for analysis.ResultsMultivariate logistic analysis showed that fish intake was inversely associated with risk of depressive symptoms in undergraduate students. After adjustment for possible confounders, the odds-ratios (95% confidence intervals) for fish intake 1–2 times/month, 1–2 times/week, 3–4 times/week, and almost every day (compared with “almost never”) were 0.78 (0.62–0.99), 0.70 (0.56–0.87), 0.67 (0.53–0.85) and 0.65 (0.46–0.92), respectively. This association tended to be stronger in women than in men.ConclusionsFrequent fish consumption in undergraduate students seems to moderate depressive symptoms. Further research is warranted to clarify the causality.

Optimal management of cavernous sinus hemangiomas remains unclear. Total microsurgical removal of these neoplasms may be extremely difficult due to their rich vascularization. Three cases of cavernous sinus hemangioma treated with low-dose Gamma Knife radiosurgery are presented. Marginal dose varied from 10 to 13 Gy. Treatment planning and radiation dosimetry were done with a goal of conformal and selective coverage of the lesion with 50% prescription isodose line using multiisocenter technique. In all cases significant shrinkage of the neoplasm was marked at 3 months after treatment. Mean volume reduction at 12 months after radiosurgery was 60% (range: 45-75%). In all patients the shrinkage of the neoplasm was accompanied by notable improvement of the preexistent oculomotor nerve palsy. No radiosurgery-related complications were met during follow-up. In conclusion, low-dose Gamma Knife radiosurgery seems to be very effective for management of cavernous sinus hemangiomas, and can be considered as a treatment modality of choice for these lesions.

The brain is frequently affected by the spread of lung cancer, and haematogenous metastasis is a common route to brain metastasis. We therefore developed an isogenic brain metastasis model of lung cancer to use the Lewis lung carcinoma cell line and analysed dynamics of neoplastic cells after extravasation. Histological analysis revealed two characteristic patterns: metastatic foci exhibiting an angiocentric pattern were designated 'perivascular proliferations'; neoplastic cells infiltrating the brain parenchyma were designated 'invasive proliferations'. Electron microscopic observation of perivascular proliferations showed that neoplastic cells were confined to the perivascular space. In invasive proliferations, however, fragments of collagen fibre were observed in the gaps between neoplastic cells, indicating that the neoplastic cells had disintegrated the pia-glial membrane. We analysed the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 by using both immunohistochemical analysis and real-time polymerase chain reaction analysis. MMP-2 expression was significantly higher in invasive proliferations. MMP-9 expression was significantly higher in day 7, but there was no significant difference in day 11. The pia-glial membrane and perivascular space are the barriers that neoplastic cells must overcome to infiltrate the brain. In conclusion, our findings suggest that brain metastasis requires two distinct processes.

Summary Objective: There is no widely accepted method to repair articular cartilage defects. Bone marrow mesenchymal cells have the potential to differentiate into bone, cartilage, fat and muscle. Bone marrow mesenchymal cell transplantation is easy to use clinically because cells can be easily obtained and can be multiplied without losing their capacity of differentiation. The objective of this study was to apply these cell transplantations to repair human articular cartilage defects in osteoarthritic knee joints. Design: Twenty-four knees of 24 patients with knee osteoarthritis (OA) who underwent a high tibial osteotomy comprised the study group. Adherent cells in bone marrow aspirates were culture expanded, embedded in collagen gel, transplanted into the articular cartilage defect in the medial femoral condyle and covered with autologous periosteum at the time of 12 high tibial osteotomies. The other 12 subjects served as cell-free controls. Results: In the cell-transplanted group, as early as 6.3 weeks after transplantation the defects were covered with white to pink soft tissue, in which metachromasia was partially observed. Forty-two weeks after transplantation, the defects were covered with white soft tissue, in which metachromasia was observed in almost all areas of the sampled tissue and hyaline cartilage-like tissue was partially observed. Although the clinical improvement was not significantly different, the arthroscopic and histological grading score was better in the cell-transplanted group than in the cell-free control group. Conclusions: This procedure highlights the availability of autologous culture expanded bone marrow mesenchymal cell transplantation for the repair of articular cartilage defects in humans. © 2002 OsteoArthritis Research Society International

Etoposide (VP16) is a drug used not only for the treatment of lymphoma but also for the collection of peripheral blood stem cells (PBSCs). We analysed the efficacy and adverse effects of collecting PBSCs and the relation between the infused cell dose and the clinical outcome in lymphoid malignancies.Investigating 30 patients with non-Hodgkin's lymphoma, one patient with Hodgkin's lymphoma, and five patients with multiple myeloma, we compared the effects of several doses of etoposide with those of CHOP or CHOP-like treatments or salvage treatments. We also analysed the relation between the amount of CD34(+) cells collected (above or below 5.0 × 10(6) /kg/day) and prognosis of these patients.We found the collected cell count to be highest in patients treated with 500 mg/m(2) of VP16 and lowest in those not treated with VP16 (P = 0.0073). A CD34(+) cell count above 100/μL on the collection day indicates that the target amount of CD34(+) cells (4.0 × 10(6) /kg) can be readily obtained and was reached most rapidly by the patients who had received 500 mg/m(2) of VP16 (P = 0.01). The longer duration of neutropenia in those patients (P = 0.000006) resulted in longer antibiotic treatment (P = 0.0052). Both progression-free survival (PFS) and overall survival (OS) were better for the patients who yielded more than 5.0 × 10(6) CD34(+) cells/kg/day (P = 0.087 for PFS and P0.033 for OS).We show here that 3 days of VP16 at 500 mg/m(2) was useful for the collection of PBSCs and that patients who yielded more than 5.0 × 10(6) CD34(+) cells/kg/day survived longer than those who yielded less.

Stereotactic radiosurgery is an alternative to conventional surgery for the treatment of trigeminal neuralgia. To better define the safety of radiosurgery and optimal technical choices, we reviewed our patient records and the literature. A total of 334 patients presenting with trigeminal neuralgia were treated between December 1992 and September 2005. A minimum of 1 year of follow-up was available for 262 patients. The mean age was 68 years (range: 30-90); 128 patients were male and 134 female. A neurovascular conflict was clearly visualized on MRI in 167 patients. Twenty-one had a past history of multiple sclerosis and 110 had already received conventional surgical treatment for trigeminal neuralgia. The intervention consisted of gamma knife radiosurgery (GKS) to the retrogasserian cisternal portion of the Vth cranial nerve. The median maximal dose used was 85Gy (range: 70-90). Actuarial curves show a plateau at 5 years for both the risk of hypoesthesia and recurrence. At 5 years, 58% of the patients remain pain-free and 83% have no trigeminal nerve disturbance. The median delay for pain cessation was 15 days. The initial pain-relief rate was 89%. None of the complications reported for the other techniques were observed. Patient selection (typical versus atypical, age, past surgery, multiple sclerosis) and details of operative technique (maximum dose, volume of nerve treated, target location, etc.) had a major influence on the probability of pain relief and toxicity risk. The details of operative technique are turning out to have a major influence on the clinical results. In our experience, high-dose (80-90Gy) retrogasserian (7-8mm from the brainstem) GKS provides the patient with a better chance of long-term pain relief and a lower risk of trigeminal nerve functional disturbance. GKS applied to the cisternal anterior trigeminal nerve using high doses provided safe and effective treatment for trigeminal neuralgia over the long term.

Preoperative morphological assessments and anatomical delineation are keys to treatment of adult patients with congenital heart disease. We report on 2 cases where morphological assessments by multidetector-row computed tomography (MDCT) were useful. Case 1. A 33-year-old male was diagnosed with atrial septal defect (ASD) complicated by mitral regurgitation (MR), tricuspid regurgitation (TR), and severe pulmonary hypertension. In establishing the diagnosis, we carefully examined and confirmed that there was no possibility of ostium primum defect or other complicating malformations. MDCT was useful for demonstrating the location and morphology of the defect, anatomical relation to the tricuspid ring and the presence or absence of complicating malformations. Case 2. A 61-year-old female was diagnosed with double-chambered right ventricle with an intraventricular pressure gradient of 80 mmHg. MDCT extensively and clearly delineated the position and shape of abnormal muscle bundles and the morphology of complicating ventricular septal defect (VSD). MDCT was also useful in the determination of specific surgical procedures and the quick understanding of the anatomy during surgery, and even in postoperative assessments of therapeutic effects.

Chondrosarcoma of rib origin is rare. A 50-year-old man without symptom was pointed out an abnormal shadow on chest X-ray. Computed tomography (CT) showed a low density mass arising from the right chest wall, and a CT-guided needle aspiration biopsy disclosed the tumor consisted of cartilage matrix with a partial necrosis. We suspected the tumor to be a chondrosarcoma of rib origin and performed a wide resection with the right 3rd and 4th ribs. The defect of the chest wall was repaired with double prolene mesh. Histological examination revealed grade 2 chondrosarcoma. Postoperative course has been uneventful for 25 months.

Little is known about the histological effect of hepatic arterial infusion with degradable starch microspheres (DSM), adriamycin (ADM), and mitomycin C (MMC) on liver metastasis of colorectal cancer. We histologically examined hepatic metastases resected following this therapy and investigated their relation to macroscopic changes in size. Neither a histological nor macroscopic effect was found in 2 patients receiving this therapy only one time. A 57-year-old woman with a solitary liver metastasis who received this therapy repeatedly (five times every 3 to 4 weeks) subsequently showed a partial response. She underwent hepatic metastasectomy 5 months after the end of the therapy. Histological examination showed that the greater part of the metastatic lesion was composed of fibrous tissues without any viable cancer cells. In conclusion, it should be noted that repeated infusions of DSM.ADM.MMC for liver metastases of colorectal cancer can have a marked histological effect even though the lesion does not show a complete response.

We investigated whether the efficacy of peroral doxifluridine and hepatic arterial 5-FU infusion on synchronous liver metastasis of colorectal cancer could be predicted based on the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in the primary colorectal lesions. Ten patients with synchronous liver metastasis of colorectal cancer were given doxifluridine (600-800 mg/body/day) orally and 5-FU (500 mg/body, once or twice a week) through the hepatic artery following resection of the primary lesions between June 1996 and July 2001. The levels of TP and DPD in the primary lesions were determined by an enzyme-linked immunosorbent assay. The level of TP, DPD, and the ratio of TP/DPD in patients with partial response (n = 4) were 89.8 +/- 30.0 U/mg protein, 23.5 +/- 25.7 U/mg protein, and 3.8 +/- 1.4, respectively, while those in patients with no response or progressive disease (n = 6) were 41.8 +/- 9.7 U/mg protein, 25.8 +/- 15.8 U/mg protein, and 2.2 +/- 1.6, showing significant difference (p0.01) in the level of TP between the groups. These results indicate that determining the level of TS in primary colorectal lesions may be useful for predicting the efficacy of this regimen for patients with synchronous liver metastasis of colorectal cancer.

Inflammatory cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor-alpha are produced in great quantities in inflamed rheumatoid joints. However, little is known about the pathogenic significance of each cytokine in the proliferative synovitis and destruction of bone and joint. We investigated the role of cytokine receptor signals transduced into cells at the foci of rheumatoid inflammation.Synovial fluid (SF) cells from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were examined for the activation of a group of cytokine receptor signaling molecules, signal transducers and activators of transcription (STAT).DNA binding of STAT1 in SF cells was observed in 8 out of 14 patients with RA, but in none of the 10 patients with OA studied, and this was prevented by preincubation of these cells with neutralizing anti-IL-6 antibody. IL-6 activated both STAT1 and STAT3 in normal peripheral blood (PB) leukocytes, and preferentially STAT1 in rheumatoid SF cells. Moreover, STAT1 activation in rheumatoid SF cells appeared to be continuous, in contrast to the transient activation in normal PB leukocytes.STAT1 and STAT3 are differentially regulated in response to IL-6 in different cell types. The continuous STAT1 activation may be of pathogenic significance in the progression and persistence of RA.

The relationship between clinicalfeatures and biochemical parameters of synovialfluid after serial intra-articular injections of sodium hyaluronate (SI-6601D) was investigated.SI-6601D (sodium hyaluronate with an average molecular weight of 8.4 x 10(5); 25mg/2.5ml/syringe) was injected intra-articularly into the knees of 25 patients with rheumatoid arthritis (RA) every week for 5 consecutive weeks. Clinical and biochemical parameters were monitored before and after injection. Clinicalfindings included pain, as a summation of 3 categories (pain at rest, pain in motion and pain in passive motion, each assessed on a 4-step rating scale), and inflammation, also as a summation of 3 categories (swelling, patellar ballotement and local warmth, each assessed on a 4-step rating scale). Pain on walking of patient was qualitatively assessed by visual analogue scale (VAS). The aspirated volume of synovialfluid (SFV) was recorded and levels of prostaglandin (PG) E2, transforming growth factor beta-1, tumor necrosis factor alpha, interleukin I receptor antagonist, chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate were measured.Significant improvement in pain symptoms (p0.0001), inflammation (p0.0001), VAS pain (p0.001) and SFV (p0.05) were observed after the 5 injections. Levels of PGE2 (p0.05) and C4S (p0.05) in the synovialfluid were significantly decreased.SI-6601D improved local clinical symptoms in RA patients by suppressing PGE2 and, therefore, may be a useful treatment for local inflammation in RA.

Fluoropyrimidine therapy for elderly colorectal cancer patients remains controversial. Tumoral levels of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and the ratio of TP to DPD determined by an enzyme-linked immunosorbent assay were compared between colorectal cancer patients aged 75 or over (elderly group, n = 25) and those 74 years or less (control group, n = 87), in order to examine the characteristics of colorectal cancers in the elderly from the viewpoint of metabolic and anabolic pathways of fluoropyrimidines. The level of TP was 78.4 +/- 47.0 unit/mg protein in the elderly group and 82.4 +/- 70.9 unit/mg protein in the control group (p = 0.86). The level of DPD was 53.7 +/- 43.1 unit/mg protein in the elderly group and 52.6 +/- 37.7 unit/mg protein in the control group (p = 0.73). The ratio of TP to DPD was 2.0 +/- 1.2 in the elderly group and 1.8 +/- 0.9 in the control group (p = 0.44). These three parameters did not differ between the groups when divided according to Dukes' stage (Dukes' A.B versus Dukes' C.D). These results suggest that there are no age-specific characteristics in relation to conversion of fluoropyrimidines such as capecitabine and doxifluridine to 5-fluorouracil (FU) and degradation of 5-FU in colorectal cancers.

In the present study, we investigated mutations of the adenomatous polyposis coli (APC) and beta-catenin genes to clarify possible molecular mechanisms underlying development of lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Male Wistar rats, 6 weeks of age, were given 2000 ppm BHP in drinking water for 12 weeks and then maintained without further treatment until sacrifice at week 25 DNA was extracted from paraffin-embedded tissues, and PCR-single-strand conformation polymorphism analysis, followed by nucleotide sequencing, was performed. No APC mutations were detected in 17 hyperplasias, but 2 of 15 adenomas (13.3%) and 8 of 20 adenocarcinomas (40.0%) showed changes within exon 1 to the mutation cluster region in exon 15. For beta-catenin, no mutations were detected in 17 hyperplasias, but 3 of 15 adenomas (20.0%) and 5 of 20 adenocarcinomas (25.0%) had alterations within or flanking codons corresponding to important phosphorylation sites. Immunohistochemical staining showed beta-catenin protein localized in the cell membranes in the surrounding normal-appearing lung and 216 hyperplasias and localized mainly in the cytoplasm and/or nucleus in 10 of 37 adenomas (27.0%) and 21 of 40 adenocarcinomas (52.5%). These results suggest that the APC-beta-catenin-T-cell factor signaling pathway is involved in the acquisition of growth advantage from adenomas to adenocarcinomas in BHP-induced rat lung carcinogenesis.

A pilot study was performed to evaluate the feasibility and efficacy of irinotecan hydrochloride (CPT-11) plus carboplatin (CBDCA) for treatment of advanced or recurrent colorectal cancer. Fifteen patients with colorectal cancer (nonresectable, 1; noncurative resection, 5; recurrent disease, 9) were treated with CPT-11 (40-50 mg/m2) plus CBDCA (70-100 mg/m2) once a week for 2-3 weeks followed by a one-week rest. This treatment was repeated until disease progression or severe toxic effects were found. The total dose of CPT-11 ranged from 135 to 1,214 (median, 467) mg/m2 and that of CBDCA ranged from 267 to 2,022 (median, 933) mg/m2. Adverse effects included nausea (grade 2) in 2 (13.3%) diarrhea (grade 2) in 2 (13.3%), leukopenia (grade 3) in 2 (13.3%), thrombocytopenia (grade 1) in one (6.7%), and hair falling (grade 3) in one (6.7%). The response rate of 14 evaluable patients was 14.3% (CR, 1; PR,1; NC,7; PD,5). The median survival time of all patients was 405 days from the start of chemotherapy. The survival time of patients with CR, PR, and NC (n = 9) tended to be longer than that of those with PD (n = 5) (p = 0.06). The median time to disease progression was 105 days. These results suggest that this combination chemotherapy is feasible and effective in the treatment of advanced or recurrent colorectal cancer.

A 38-year-old male was admitted to our hospital complaining of dysphagia, sore throat and fever. An upper GI series revealed a "double-barrelled" esophagus. Endoscopic examination of the esophagus showed multiple ulcers and mucosal bridges resulting from laceration of the submucosal layer. An acute ulcer of the stomach was also found. Fasting and total parenteral nutrition for several weeks failed to bring about any changes in the endoscopic findings. As treatment, the mucosal bridges throughout the esophagus were divided with a diathermy knife under endoscopic control. Soon after the procedure, the patient's symptoms disappeared completely, and the massive dissection of the esophagus had improved except for slight depressions.

A uricosuric agent, bucolome, has been shown to intensify the anticoagulant effect of warfarin. The aims of the present study were to clarify its mechanism(s) and to apply in vitro approaches for predicting this potentially life-threatening in vivo interaction. An in vivo study revealed that Japanese patients given warfarin with bucolome (300 mg/day, n = 21) showed a 1.5-fold greater international normalized ratio than those given warfarin alone (n = 34) despite that the former received a 58% smaller warfarin dose than the latter. Enantioselective assays revealed that bucolome increased plasma unbound fractions of (S)- and (R)-warfarin by 2-fold (p.01), reduced unbound oral clearances of (S)- and (R)-warfarin by 84 (p.01) and 26% (p.05), respectively, and inhibited the unbound formation clearance for (S)-warfarin 7-hydroxylation by 89% (p.01). In contrast, bucolome elicited no appreciable changes in the plasma unbound (S)-warfarin concentration versus the international normalized ratio relationship. In vitro studies with recombinant human cytochrome P-450 2C9 and liver microsomes showed that bucolome was a potent mixed-type inhibitor for (S)-warfarin 7-hydroxylation, with K(i) of 8.2 and 20.2 microM, respectively. An in vitro model incorporating maximum unbound bucolome concentration in the liver estimated as a sum of hepatic artery and portal vein concentrations and in vitro K(i) made an acceptable prediction for bucolome-induced reductions in in vivo total (bound + unbound) oral clearance, unbound oral clearance, and unbound formation clearance for (S)-warfarin. In conclusion, the augmented anticoagulant effect of warfarin by bucolome due to the metabolic inhibition for pharmacologically more potent (S)-warfarin may be predictable from in vitro data.

Emergent coronary artery bypass grafting (CABG) for the treatment of acute coronary syndrome has increased the operative mortality. Forty-nine patients underwent urgent or emergent CABG for the treatment of medically refractory unstable angina in 10 patients, and for acute myocardial infarction (AMI) in 39 patients. Ten operative deaths were occurred in the AMI patients, and the mortality was 20 percent. The preoperative risk factors were evaluated in 10 patients who died in the operative period. Cardiopulmonary resuscitation before operation, intra aortic balloon pumping, the use of catecholamine, and intubation with or without percutaneous cardiopulmonary support revealed operative risk factor. Because the patients who have preoperatively shock, it seemed to be needed that the rescue of the patients should improve the clinical results for urgent or emergent CABG.

To identify the optimal treatment of rheumatoid shoulder, we analyzed the clinical results of shoulder surgeries according to each type of shoulder destruction pattern.Forty-seven shoulder surgeries for rheumatoid arthritis (18 arthroscopic synovectomies, 10 total shoulder replacements, 19 humeral head replacements) were assessed clinically and compared in regard to 5 different destruction patterns of rheumatoid shoulder (nonprogressive, arthrosis-like, erosive, collapse, and mutilating patterns).For nonprogressive-type shoulders, we were able to obtain both pain relief and range of motion (ROM) improvement with arthroscopic synovectomy. For erosive-type shoulders, we could obtain pain relief but no ROM improvement with synovectomy; and we obtained both pain relief and ROM improvement with prosthetic replacement. For the collapse-type shoulders, we could not obtain pain relief or ROM improvement with arthroscopic synovectomy, but did obtain pain relief with prosthetic replacement. For mutilating-type shoulders, we could obtain only pain relief with prosthetic replacement. The results of the various surgeries for rheumatoid shoulder were distinctly different depending on the shoulder destruction patterns.These findings could be of value for the selection of treatment, including a surgical procedure, for rheumatoid shoulders. For the nonprogressive-type and for erosive-type shoulders before bone destruction progresses, arthroscopic synovectomy should be selected. For erosive-type shoulders after bone destruction, for the collapse-type, and for mutilating-type shoulders, prosthetic replacement should be selected. In regard to the prosthetic replacement, the humeral component should be cemented because the incidence of migration in noncemented humeral component procedures was high.

A 33-year-old male was admitted because of severe neutropenia (55/microliter) in 1985. A diagnosis of autoimmune neutropenia was not made. CD4+ T-lymphocyte count was 128/microliter and CD4/CD8, 0.1, though the titers of immunoglobulins were in normal range. Nine times examinations of CD4+ T-lymphocyte count resulted in 5 times lower counts than 300/microliter between 1985 and 1993. His HIV (type 1 and type 2) studies were negative. He suffered from EB virus infection in 1987. The titers of VCA-IgG and EA-IgG had been elevated for half a year after that. He was operated polyp-like tumors in bilateral nasal cavities on February in 1994. The diagnosis was Burkitt's lymphoma that was also demonstrated by in situ hybridization using EB virus RNA. He was treated with a modification of COPBLAM III, but he died on June in 1994. Autopsy revealed tumor cell infiltrations in multiple organs. We suspect that he developed Burkitt's lymphoma 82 months later, when he had complicated EB virus infection in condition of idiopathic CD4+ T-lymphocytopenia caused by unknown origin.

Hydroxyapatite (HA) granules of 100 to 300 microm, 0.9 to 1.2 mm and 3.0 to 5.0 mm were mixed in a ratio of 10:45:45 and packed into massive bone deficiencies in revision operations for total hip arthroplasty. We did not use additional graft or cup support for deficiencies of the lateral and medial wall. The procedure was carried out in 40 hips between 1986 and 1992. The radiographic spaces seen at the interface between HA and bone immediately after surgery disappeared within three months. Some spaces appeared between HA granules near the bone in the lateral part of two joints, and three sockets migrated in patients with severe segmental and cavitary deficiencies. Direct bonding of HA to bone was observed radiologically without morphological changes, except in the three joints with migration. All patients could walk without pain but the three with definite loosening needed crutches.

We investigated the late negative components of the contingent negative variations (CNVs) in the verbalization task. Six subjects were instructed to perform three different motor tasks, jaw opening, vocalization of a meaningless sound and that of a word, in response to a sound stimulus following a visual warning stimulus with interstimulus interval of 4.0 sec. The electroencephalograms (EEGs) were recorded from the midline-central (Cz), left and right temporal areas (T3 and T4) and frontal areas (F7 and F8). EEGs were averaged 16 times using the visual stimulus pulse as a trigger to obtain the CNVs in each motor task. There was no significant difference between the tasks of the jaw opening and vocalization of the sound in the CNV amplitudes at bilateral electrodes. However, the amplitudes of the CNVs at the left frontal and temporal areas were significantly larger in the case of vocalization of the word than in that of jaw opening (p0.05). On the other hand, there was no significant difference between these two tasks in the CNV amplitudes at the right frontal and temporal areas. Our results suggested that the CNVs generated over the left hemisphere might reflect the brain activities involved in language production.

Until recently, the only effective treatment for bleeding esophageal varices was surgery, including portal-systemic shunts, nonshunting operations, and selective shunts. New operations were developed from the neccessity to find a better therapeutic modality for the treatment. This article describes the history of development of surgical treatment for portal hypertension as well as introducing the outline of several such procedures. The history of nonoperative treatments, especially endoscopic injection screlotherapy, is also described: Endoscopic sclerotherapy as a treatment for bleeding esophageal varices had been employed before many definitive surgical procedures. In accordance with the development of fiberoptic endoscopy, endoscopic sclerotherapy came into prominance. The less invasive treatment is appreciated and popularized even among surgeons today, who once believed that shunt operation (or nonshunting operation) was the best modality of treatment for esophageal varices. Finally, this article provides readers with a simplified guide to Japanese participation in the development of treatment for esophagogastric varices.

CGP 41251 (4'-N-benzoyl staurosporine, CAS 120685-11-2) has been shown to exert increased selectivity for the inhibition of protein kinase C (PKC) activity. In the present study the effect of CGP 41251 formulated in gelucire as an antitumor agent was studied in various types of murine and human tumor models. When administered at a dose of 75 mg/kg 3 times daily for 9 days, CGP 41251 prolonged the life span of the mice bearing B16 melanoma (ILS = 36%). CGP 41251, administered orally at doses of 25-225 mg/kg once daily for 9 days, however, did not show distinct efficacy in four kinds of murine tumor models (B16 melanoma, colon 26, colon 38 and M5076). In s.c.inoculated human tumor xenograft models, CGP 41251, administered orally at a dose of 200 mg/kg once daily for 4 weeks showed a broad antitumor spectrum. CGP 41251 inhibited the growth of gastric cancer (H-55), colorectal cancer (H-26), breast cancer (H-31) and lung cancer (H-74 and LC-376) with inhibition rates of 58-80%. In a histopathologic study, increase in central necrosis and condensed nuclei and vacuolar degeneration were observed, but there was no structural destruction by the treatment of CGP 41251. In addition, CGP 41251 decreased the number of PCNA (proliferating cell nuclear antigen) immunoreactive cells in human tumor cells H-55, H-26 and H-74. These results indicate that CGP 41251 shows a broad antitumor spectrum against human tumors, and it is suggested that CGP 41251 is a promising oral antitumor agent which has a novel mechanism of action.

The integrin LFA-1 (CD11a/CD18) is a cell surface adhesion molecule required for leukocyte extravasation and subsequent immune and inflammatory responses. Rapid transition between nonadherent and adherent states of LFA-1 is of key importance to Ag-specific recognition of T lymphocytes. In this paper, LFA-1-mediated adhesiveness of peripheral blood (PB) and synovial fluid (SF) T lymphocytes to affinity-purified ICAM-1-coated plates was studied in patients with rheumatoid arthritis (RA) and in patients with non-RA panels, including osteoarthritis, ankylosing spondylitis, erythema nodosum, pseudogout, and pustulosis. LFA-1-mediated adhesiveness of SF T lymphocytes was not observed in any of the 10 non-RA patients studied, although cross-linking of the TCR on lymphocytes from these patients rapidly converted LFA-1 to an adhesive state. In contrast, SF T lymphocytes from 10 of 12 RA patients exhibited LFA-1-mediated adhesiveness without a requirement for cross-linking of the TCR. No difference was seen in the cell surface density of LFA-1 between non-RA and RA T lymphocytes, suggesting that the difference in adhesiveness was due to a high avidity state of LFA-1 on SF T lymphocytes in RA. Furthermore, exposure of PB T lymphocytes, which showed a low avidity state of LFA-1, to whole SF from RA patients that was depleted of T lymphocytes could induce a high avidity state of LFA-1 in vitro. Cellfree SF from RA patients also could stimulate adhesiveness, although to a lesser extent. These data suggest the existence of a LFA-1-activating environment that is selectively found in SF from RA patients.

A mediastinitis after a graft replacement of the ascending aorta is serious complication and sometimes could be lethal. We have experienced two cases of such a condition, recently. In both cases, the debridement of the mediastinum and omental transposition were performed. Case 1 had a recurrent mediastinitis due to residual dead space infection, but was cured by a percutaneous drainage and a continuous irrigation. In case 2, the omentum was carefully positioned to occupy the dead space around the graft, because of the experience of the first case and gave a good result. We believe that omental transposition is an effective treatment for the postoperative mediastinitis.

A case was 33 years old man who had complained chest pain during exercise. He was diagnosed anomalous origin of the left coronary artery from the pulmonary artery by coronary angiography. At operation, left main coronary artery originated from the posterior wall of the pulmonary artery. Numerous retrograde flow was seen through left coronary artery during aortic cross clamping. The left coronary ostium was closed, because sufficient extracardial anastomosis to coronary artery should be thought. The post operative course was uneventful and the patient is asymptomatic. The selective bronchial artery angiography was performed and it demonstrated collaterals between the bronchial artery and the left circumflex artery. The Thallium scintigraphy had showed ischemia of antrolateral wall of the left ventricle before operation, but postoperatively there was no ischemic redistribution.

The development of a new strip biopsy technique for endoscopic mucosectomy utilizing endoscopic saline injection and a double-channel endoscope permits the safe and simple resection of superficial type early gastric cancer which has been difficult to perform with conventional polypectomy techniques. Preresection assessment of the depth of invasion and postresection assessment of efficacy are important with regard to treatment of early gastric cancer, but conventional endoscopic ultrasonography employed for this purpose requires special equipment and involves intricate procedures. An ultrasonic probe which can be used endoscopically has recently been developed and is currently in the trial stage. The authors have conducted studies with respect to a 7.5 MHz radial scanning type Miniature Ultrasonic Probe as well as a 20 MHz manual linear scanning type Sonoprobe System. Experimental studies indicated that the former type is capable of delineating postresection ulcers, while the latter permitted delineation of tumors as hypoechoic images in 9 of 11 cases of early gastric cancer.

We evaluated endogenous serum erythropoietin (Epo) levels in 14 normal subjects (eight males and six females) after a single 400-ml phlebotomy. The subjects were followed up for 56 days. The hemoglobin (Hb) values of both males and females decreased to a nadir on days 3 to 7 post-phlebotomy. Hb values gradually increased, but did not completely recover to pre-phlebotomy levels by day 56. Serum Epo levels increased after 6 h post-phlebotomy, to 20.1 +/- 5.4 (mU/ml) in males and 20.7 +/- 7.0 in females, from the pre-phlebotomy levels of 14.6 +/- 4.0 in males and 13.4 +/- 4.1 in females, respectively. Epo levels continued to increase to peak levels of 25.5 +/- 6.3 in males and 28.7 +/- 11.5 in females on days 7 to 14 and thereafter decreased until day 56. Thus, the Epo response to a 400-ml phlebotomy was relatively small in magnitude and was not sufficient to initiate a significant increase in erythropoiesis. This finding suggests that the administration of recombinant human erythropoietin (rHu-Epo) may be effective for the prompt correction of anemia induced by autologous blood donation and for increasing the volume of predonated autologous blood.

The purpose of this study was to clarify the significance of immunohistological staining for PCNA/cyclin in human colorectal lesions. Our results: The PCNA-positive cells existed at the bottom of colonic tubuli in the normal and hyperplastic conditions. In the neoplastic lesions, however, the positive cells were existed at the relatively surface of the mucosa (chi 2: P less than 0.01) and distributed irregularly from the bottom to the top of carcinoma tissue. These results suggested that immunohistological staining for PCNA would specifically detect the cell proliferation and be beneficial for practical use and clinical application of the diagnosis of the colorectal lesions.

Esophageal duplication cyst associated with pericardial defect in a 57-year-old man is reported. Differential diagnosis was very difficult in the preoperative examination. The tumor was a cyst and its wall was a perfect replica of normal esophagus e.g. esophageal duplication, and total left pericardial defect also was found at the operation. There was no malignant or inflammation findings in the excised specimens. The association of esophageal duplication cyst associated with pericardial defect is very rare.

The effect of cupric acetate on dimethylnitrosamine (DMN)-induced hepatocarcinogenesis in rats was investigated. The surviving rats in the group given DMN (25 ppm) in the drinking water alone were killed at 26 weeks and it was found that 12 of 16 rats had developed liver tumors. In the group given DMN and cupric acetate (sc injections of 2 mg of Cu/kg of body weight once a week for 26 weeks), 7 of 22 rats developed liver tumors. The incidence of liver tumors in rats given DMN and cupric acetate was thus only about 40% of that in rats given DMN alone. No tumor was observed in the group given saline or cupric acetate alone. The thymidine incorporation into the liver DNA of rats was measured at 2 and 4 weeks after the start of the carcinogenicity experiment. The thymidine incorporation into the liver DNA of rats given DMN was significantly suppressed by the administration of cupric acetate. The methylation of liver DNA in rats given a single dose of DMN was also significantly suppressed by sc injection of cupric acetate; the formation of both O6-methylguanine and 7-methylguanine was reduced. This result suggests that sc injection of cupric acetate may have a suppressive effect on the initiation of carcinogenesis in the liver.

Dimethylnitrosamine was administered to mice by ip injection once a week for 3 weeks and a high incidence of lung tumor was found 6 approximately 8 months after the final injection. In experiment I, the incidence of mice with lung tumors was 74% and the average number of nodules per mouse was 15.6 within 6.0 months after the final injection of dimethylnitrosamine. In mice given aluminium pretreatment, these values decreased to 65% and 6.7 (P less than 0.05), respectively. In experiment II, the incidence of mice with lung tumors was 100% and the average number of nodules per mouse was 8.7 within 7.5 months after the final injection of dimethylnitrosamine. In mice given aluminium pretreatment, these values decreased to 79% and 4.6 (P less than 0.05), respectively.

Dose-related suppression of the 3H-thymidine incorporation into liver DNA of rats after a single injection of dimethylnitrosamine by copper pretreatment was observed. The 3H-thymidine incorporation was not decreased by cadmium pretreatment. On the other hand, the 3H-thymidine incorporation into liver DNA of partially hepatectomized rats was decreased by both copper and cadmium pretreatments. Thymidine kinase activity in the liver of rats treated with dimethylnitrosamine was also decreased by copper pretreatment, but the enzyme activity was not decreased by cadmium pretreatment. Copper accumulation in the liver of copper-administered rats was predominantly in the nuclear fraction, followed by the soluble fraction. Cadmium accumulation in the liver of cadmium-administered rats was predominantly in the soluble fraction, followed by the nuclear fraction. Copper accumulation in the nuclear fraction may suppress the induction of thymidine kinase in the liver of rats by dimethylnitrosamine.

The concentration of total bile acids in the serum was measured in thirty-three patients before and after esophageal transection for esophageal varices, in an attempt to determine the influence of this surgery on the naturally developed portasystemic shunt and also the liver function relating to the bile acid metabolism. The levels of fasting total bile acids in the serum were decreased on the first postoperative day, but gradually increased up to the preoperative levels by the twenty-first postoperative day. The maximum value of total bile acids, as determined in ursodeoxycholic acid tolerance tests, was decreased after the esophageal transection (p less than 0.01). The average of the maximum total bile acids in UDCA tolerance tests was 79.5 microM in the preoperative stage, and 61.0 microM in the postoperative stage. This finding suggested that esophageal transection abolished the portasystemic collaterals and contributed to an increase in efficient hepatic blood flow, which led to the improvement of liver function.