[Current topics of prion disease].
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14-3-3 Proteins↗
Biomedical subjects
H Furukawa
Publications and source records attributed to H Furukawa.
Involvement of nitric oxide in phencyclidine-induced place aversion and preference in mice.
The present study investigated the involvement of nitric oxide (NO) in phencyclidine (PCP)-induced place aversion and preference in the place conditioning paradigm. PCP-induced place aversion in naive mice was dose-dependently attenuated by administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a NO synthase (NOS) inhibitor, during the conditioning. The NOS activity and dopamine (DA) turnover in the hippocampus in mice showing PCP-induced place aversion were decreased, such changes being restored by administration of L-NAME during the conditioning. On the other hand, PCP-induced place preference in mice pretreated with PCP for 28 days was not attenuated by administration of L-NAME during the conditioning. Although NOS activity was not changed, the DA turnover in the cerebral cortex was increased in mice showing PCP-induced place preference. In mice pretreated with L-NAME and PCP for 28 days before the place conditioning paradigm, PCP neither induced place preference, nor changed the NOS activity or DA turnover. These results suggest that NO is involved in the acquisition of PCP-induced aversive effects, and in the development of PCP-induced preferred effects. Further, the functional change of the DAergic neuronal system mediated by NO in the hippocampus and cerebral cortex may be necessary for the expression of aversive effects and development of preferred effects, respectively, induced by PCP.
Animals↗
Comment on "Hydrodynamic coarsening of binary fluids"
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Journal Article↗
Fish oil diet affects on oxidative senescence of red blood cells linked to degeneration of spleen cells in mice.
The effect of dietary polyunsaturated fatty acids and alpha-tocopherol supplementation on erythrocyte lipid peroxidation and immunocompetent cells in mice was studied comparatively using seven dietary oils (15% oil/diet, w/w) including fish oil rich in eicosapentaenoic acid (EPA, 20:5, n-3) and docosahexaenoic acid (DHA, 22:6, n-3). A 43% increase in spleen weight, about twice as many spleen cells and no change in the subpopulations of spleen cells, as well as a significant depression of mitogen-induced blastogenesis of both T and B cells in the spleen were observed in mice fed fish oil for 30 days in comparison with soybean oil diet-fed mice. In the fish oil diet-fed mice, membranous lipid hydroperoxide (hydroperoxides of phosphatidylcholine and phosphatidylethanolamine) accumulation as a marker of oxidative senescence in red blood cells (RBC) was 2.7-3.5 times higher than that in mice fed soybean oil, although there was no difference in the plasma phosphatidylcholine hydroperoxide concentration. In spite of the supplementation of alpha-tocopherol to up to 10 times the level in the basal diet, the degeneration of spleen cells and the stimulated oxidative senescence of RBC found by the fish oil feeding could not be prevented. The results suggest that oral intake of excess polyunsaturated fatty acids, i.e. EPA and DHA, in a fish oil diet can lead to acceleration of membrane lipid peroxidation resulting in RBC senescence linked to the lowering of immune response of spleen cells, and that supplementation of alpha-tocopherol as antioxidant does not always effectively prevent such oxidative degeneration as observed in spleen cells and RBC in vivo.
Animals↗
Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.
To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.
Animals↗
Intracranial self-stimulation increases differentially in vivo hydroxylation of tyrosine but similarly in vivo hydroxylation of tryptophan in rat medial prefrontal cortex, nucleus accumbens and striatum.
We have examined using microdialysis the effect of intracranial self-stimulation (ICSS) on the in vivo hydroxylation rate of tyrosine and tryptophan in the medial prefrontal cortex (mPFC), nucleus accumbens (NAC) and striatum (STR). A decarboxylase inhibitor NSD-1015 was included in the perfusate, which enabled the simultaneous measurement of 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) as an index of the in vivo hydroxylation level of tyrosine and tryptophan. When rats were exposed to 1 h of ICSS at the medial forebrain bundle (MFB), their extracellular levels of DOPA significantly increased in the mPFC, NAC and STR, but with a different magnitude and time course. The same stimulation produced a delayed increase in extracellular 5-HTP, compared to DOPA, in these brain regions. The profile of 5-HTP response demonstrated no apparent difference among the regions. These findings indicate that ICSS of the MFB can increase differentially the in vivo hydroxylation of tyrosine but similarly the in vivo hydroxylation of tryptophan in the mPFC, NAC and STR.
5-Hydroxytryptophan↗
Anti-tumor-promoting effects of isoflavonoids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.
As a part of screening studies for anti-tumor promoters, fifteen isoflavonoids isolated from plants of the genus Millettia (Leguminosae) were evaluated by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All of the compounds tested in this study showed inhibitory activity against EBV, without showing any cytotoxicity. Auriculasin (11) and millepurone (13), which is an oxidized isoflavone analogue, both having one or more prenyl side-chains and a 3',4'-dihydroxyphenyl group in the molecule, showed more potent activity than any of the other compounds tested. Furthermore, millepurone (13) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The results of the present investigation indicate that some of these isoflavonoids might be valuable anti-tumor promoters.
Animals↗
Gelatin-containing diphtheria-tetanus-pertussis (DTP) vaccine causes sensitization to gelatin in the recipients.
Gelatin-specific T cell response was performed to determine whether a series of vaccinations with gelatin-containing DTP is a primary sensitization process in gelatin allergy. Thirty-seven recipients with gelatin-containing DTP who developed adverse reactions after vaccination and eight recipients of DTP without gelatin who also developed adverse reactions were studied. In addition, 10 subjects receiving gelatin-containing vaccine and 10 subjects inoculated with non-gelatin vaccine who did not show any adverse reactions were also investigated. All subjects inoculated with gelatin-containing DTP vaccine showed positive T cell responses against gelatin, however, occurrence of adverse reactions did not correlate with T cell responses. We conclude that DTP vaccine containing gelatin induces sensitization to gelatin in the recipients, but the mechanism of local reactions remains unknown.
Child↗
Prolongation of canine liver allograft survival by a novel immunosuppressant, FTY720: effect of monotherapy and combined treatment with conventional drugs.
BACKGROUND: The immunosuppressive effect and other properties of a novel immunosuppressant, FTY720, have been studied mostly in the experimental transplantation of various extrahepatic organs. In this experiment, we evaluated the antirejection potency and adverse effects of this agent on liver grafts using a canine liver transplantation model. METHODS: Forty-eight orthotopic liver transplantations were performed by the standard technique under a veno-venous bypass. Liver recipients were divided into two studies: a single-dose study with FTY720 at various doses and a combined dose study with conventional immunosuppressants (cyclosporine or tacrolimus) alone and combined with FTY720. Survival, biochemical and hematological tests, blood levels of immunosuppressants, and postmortem histology were determined. RESULTS: The median survival of untreated control animals was 9 days, whereas treatment with FTY720 at a dose of 0.1 mg/kg/day prolonged graft survival to 49.5 days. FTY720 at 1 mg/kg/day showed a slight but insignificant prolongation to 16 days, but when the dose was increased to 5 mg/kg/day, the graft was rejected at 10 days. The combination of FTY720, 0.1 mg/kg/day, with a subtherapeutic dose of cyclosporine, 5 mg/kg/ day, prolonged median animal survival from 40 days with cyclosporine alone to 74 days. A combination of FTY720 (0.1 mg/kg/day) with tacrolimus (0.5 mg/kg/ day) compromised animal survival, reducing survival from 83.5 days with tacrolimus alone to 30.5 days due to infectious complication and emaciation by overimmunosuppression. No evident drug-induced side effects were observed. CONCLUSIONS: FTY720 has a potent immunosuppressive effect when used alone at 0.1 mg/kg/day in canine liver transplantation. FTY720 is a promising candidate for future clinical application in orthotopic liver transplantation.
Animals↗
1,1-Dimethylallylcoumarins potently suppress both lipopolysaccharide- and interferon-gamma-induced nitric oxide generation in mouse macrophage RAW 264.7 cells.
We investigated the suppressive effects of 16 coumarin-related compounds on both lipopolysaccharide (LPS)- and interferon (IFN)-gamma-induced nitric oxide (NO) generation in a mouse macrophage cell line, RAW 264.7. Notably, coumarins possessing prenyl unit(s) were found to be highly active, a tendency consistent with our previous study. Among the coumarins tested, 1,1-dimethylallylcoumarins showed the highest inhibitory activity. Western blotting analysis revealed that they inhibited NO generation by suppressing inducible NO synthase (iNOS) protein expression. Our ongoing studies suggest that coumarins are prominent natural compounds that attenuate excessive and prolonged NO generation at inflammatory sites.
Animals↗
K-ras point mutation in the nerve plexuses around the superior mesenteric artery in resectable adenocarcinoma of the pancreatic head: distribution pattern and related factors.
BACKGROUND: Adenocarcinoma of the pancreas is likely to spread into the nerve plexuses around the superior mesenteric artery (SMA) at a microscopic level. Since there has been no detailed report on how minute cancer invasion is distributed among the peri-SMA plexuses or which cases are more vulnerable to such an event, it has long been controversial how to treat this area when resecting the pancreatic head cancer. HYPOTHESIS: The K-ras mutation assay is more sensitive than the conventional histologic diagnosis in detecting minute cancer invasion around the SMA. DESIGN: Prospective consecutive series. SETTING: Cancer center hospital. PATIENTS AND METHODS: The entire circle of the peri-SMA tissues was obtained from 24 patients who had received an extended pancreatectomy for adenocarcinoma of the pancreatic head. They were divided into right and left hemicircular samples (48 samples), and each sample was used for both histologic and genetic diagnoses. Since all patients' primary tumors were positive for point mutation at codon 12 of the K-ras gene, the presence or absence of the mutation was determined for the peri-SMA plexuses using the mutant allele specific amplification method. RESULTS: Compared with results of the histologic examination, the K-ras mutation assay was more sensitive in detecting positive findings in the peri-SMA plexuses (12 samples from 9 patients). According to the distribution of the K-ras mutation into the right- and left-half samples, 24 patients were classified into the following 4 patterns (right/left): negative/negative in 15 patients; positive/negative in 6 patients; positive/positive in 3 patients; and negative/positive in 0 patients. In 3 patients who showed a positive/positive pattern in the genetic diagnosis, their right-half samples included more cancer cells that were detectable by routine microscopy. There was no relation between K-ras mutation and lymphatic invasion, while K-ras mutation was particularly related with the invasion of portal vein (P =.04) and posterior peripancreatic tissues (P =.002). All 3 patients with K-ras mutation in bilateral plexuses were classified by the TNM staging system as T4 using Union Internationale Contre le Cancer classification. CONCLUSIONS: The K-ras mutation (at codon 12) assay indicated a simple and regular pattern of cancer extension into the nerve plexuses around the SMA from adenocarcinoma of the pancreatic head: (1) The left half of the plexus was unlikely to be involved by cancer in cases in which the right half was intact. (2) Cancer extension into the peri-SMA plexuses occurred after the posterior confine of the pancreas had been involved by direct invasion from the primary pancreatic tumor. (3) The left half was not involved in cancerous tumors classified as T1 to T3 but was occasionally involved in those classified as T4 tumors. These data seem to provide a useful indicator of some additional treatments (resection, irradiation, etc) for the peri-SMA region when a locally advanced pancreatic head cancer is treated with a curative intent.
Adenocarcinoma↗
Penetrating knife injury to the heart.
A 39-year-old man attempted to kill himself using a small knife to penetrate the left anterior chest wall because of trouble at work and with his girlfriend. On arrival at the emergency room, his consciousness was not clear and vital signs were unstable. The knife remained vertically located in the left anterior chest wall. A large left hemothorax was identified by chest X-ray, and moderate cardiac tamponade was detected by echocardiography. Left-sided chest drainage was performed by inserting a chest drainage tube, and about 2500 ml of hemorrhagic effusion was drained. An emergency operation was performed to relieve the cardiac tamponade and repair the penetrating cardiac injury. About an hour after arrival at the emergency room, a median sternotomy was performed in the operating room. The knife had injured the surface of the right ventricular outflow tract, the left lung, and the 3rd intercostal artery and vein. Cardiopulmonary bypass was immediately prepared for the repair of the cardiac injury. The wounds were successfully repaired with pledgeted sutures under cardiac beating. The postoperative course was uneventful with no sign of infection. The patient was discharged at 9 days after the operation. Here we have reported a case of successful surgical repair of a penetrating knife injury to the heart, which was managed by immediate resuscitation and emergency surgery.
Adult↗
Surgical repair of postinfarction ventricular septal rupture.
OBJECTIVES: Postinfarction ventricular septal rupture is fatal without surgical repair because of heart failure and secondary multiple organ failure. We investigated surgical results of postinfarction ventricular septal rupture and discussed the surgical strategy of postinfarction ventricular septal rupture. METHODS: Twelve patients (mean age 71.3 +/- 7.4 years, with range from 61 to 81 years) underwent surgical repair of postinfarction ventricular septal rupture, from 1990 to 1998 in our Institute. There were 6 women and 6 men. The ventricular septal rupture was anterior in 10 patients and inferior in 2. The operative technique for anterior ventricular septal rupture was reconstruction of the septum with a Dacron patch after infarctectomy, according to the method of Daggett et al. For posterior ventricular septal rupture, reconstruction of the septum with a Dacron patch after infarctectomy was performed and the ventricular incision was closed with a two-layer patch. Coronary artery bypass grafting was performed in 5 patients for severe proximal coronary artery stenosis using saphenous vein grafts. RESULTS: Overall hospital mortality was 0%. A postoperative residual shunt was recognized in 3 patients, but all were well-controlled conservatively and re-operation was not needed. The patients have been followed up for a mean of 59.5 months. There have been two late deaths due to non-cardiac problems. Acturial survival rate for the 12 patients was 90% at 1 year and 75% at 5 years. CONCLUSIONS: The Daggett method is simple and fast, and is an effective and reliable technique for the repair of ventricular septal rupture.
Aged↗
Aneurysms in the ascending aorta adherent to the sternum after cardiac surgery.
Sternotomy in a patient with an aneurysm in the ascending aorta adherent to the sternum after cardiac surgery can result in fatal hemorrhage or brain damage unless the distal ascending aorta can be identified and secured immediately. A left anterolateral thoracotomy was used in three patients with adherent aneurysms. The distal ascending aorta was isolated, and dissection was performed between the aneurysm and the sternum. There was no complication. This method was safe, and blood loss was minimized.
Adult↗
Effects of phencyclidine on behavior and extracellular levels of dopamine and its metabolites in neonatal ventral hippocampal damaged rats.
RATIONALE: The use of neonatal hippocampal lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia. OBJECTIVE: To examine the role of NMDA neurotransmission in the neonatal ventral hippocampal damaged rat. METHODS: In initial experiments, we compared the effects of mild environmental stress (HAB) and the injection of saline and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. We also examined the effects of a single injection of phencyclidine (PCP, 10 mg/kg, IP) on locomotor activity and extracellular levels of dopamine (DA) and its metabolites in the nucleus accumbens (NAc) of lesioned and sham-operated rats using an in vivo brain microdialysis method. RESULTS: Compared with sham-operated controls, the lesioned rats showed increased locomotor activity at postnatal day 56 (PD56) but not at PD35 after HAB and MAP administration. Similarly, the lesioned rats showed increased locomotor activity at PD56 but not at PD35 after PCP administration. Unexpectedly, the increase in DA levels was significantly greater in the sham-operated rats than in the lesioned rats. CONCLUSIONS: The results suggest that neonatal hippocampal lesioned rats are accompanied by the dysfunction of NMDA neurotransmission. They also suggest that hyperresponsiveness to PCP following neonatal hippocampal lesions does not depend on the extracellular DA concentration in the NAc.
Animals↗
Observed localization of the long-term cultured rat adherent natural killer cells in mammary tumor tissues.
Adherent natural killer (A-NK) cells were isolated from splenic lymphocytes and treated with long-term culture in the presence of recombinant interleukin-2 (rIL-2). Immunocytochemical and flow-cytometric analysis revealed that most of the A-NK cells strongly expressed lymphocyte-function-associated antigen 1 (LFA-1alpha, and LFA-1beta) throughout the incubation. All A-NK cells from 8- to 150-day cultures, particularly those cultured for 8 days, showed significant cytolytic activity against all targets. Analysis of the tissue distribution of the injected [3H] uridine-labeled A-NK cells demonstrated that, in the first 3 h, most (over 60%) cells localized in the lungs, and that most cells remained temporally within the cavities of blood capillaries of the lungs and moved gradually into lymphoid and other tissues. Peritumoral injection of various kinds of adjuvant, particularly Freund's complete adjuvant (FCA) plus bacillus Calmetee-Guerin (BCG), resulted in a marked accumulation of [3H]A-NK cells in mammary tumor tissues 24 h after injection, and simultaneously in the formation of vessels resembling high-endothelium venules (HEV), infiltration of LFA-1+ lymphocytes and expression of the ICAM-1 molecule on the tumor cells in the sites of tumor tissues. When 30 x 10(6) A-NK cells were intravenously administered, significant retardation of tumor growth and prolongation of survival of tumor-bearing rats were observed in the groups that received the prior injection of adjuvants, especially FCA + BCG and Freund's incomplete adjuvant (FIA) + BCG. The suppressive effect of combination therapy on tumor growth was blocked effectively by the injection of anti-ICAM-1 mAb. These results indicate that the prior injection of proper adjuvant into the peritumoral region is effective for the selective accumulation or infiltration of A-NK cells into the sites of tumor tissues, and results in the marked retardation of tumor growth.
Adjuvants, Immunologic↗
Rhabdomyosarcoma presenting as an anterior cervical mass in an adult: report of a case.
We report herein the case of a 61-year-old man who was referred to our hospital for treatment of a rapidly growing tumor in the right anterior cervical region. A 13 x 14 x 15 cm mass was palpated on physical examination. Computed tomography (CT) findings indicated a thyroid tumor, but cytology results suggested rhabdomyosarcoma. A tumor, measuring 9.3 x 7.2 x 5.2 cm and weighing 220 g, was resected and histopathological examination confirmed a diagnosis of rhabdomyosarcoma. Cervical rhabdomyosarcoma is rarely found in adults.
Diagnosis, Differential↗
Late-type recurrence at the port site of unexpected gallbladder carcinoma after a laparoscopic cholecystectomy: report of a case.
A 73-year-old woman had a laparoscopic cholecystectomy for unexpected gallbladder cancer and 9 days later underwent both a liver bed resection and lymph node dissection. Four years later, she underwent a further resection of a port site recurrence of gallbladder cancer and no other site of recurrence was observed. The seeding of cancer cells during the removal of the resected gallbladder might have caused this tumor. This case may show that the port site recurrence did not necessarily indicate an incurable stage of the disease. In addition, an excision of the recurrent tumor also appeared to eliminate the disease in the patient.
Abdominal Muscles↗