Search

A 70s woman with a history of asthma and dyslipidemia underwent a robot-assisted abdominoperineal resection for rectal cancer. The ports were placed as per the method of Shizuoka Cancer Center and no intraoperative complications were observed. The colostomy was constructed in the left lower abdomen by the retroperitoneal route. The 12-mm port part was closed in 2 layers, the fascia and dermis, and the 8-mm port part was closed only in the dermis. The postoperative course was good; however, the patient vomited 10 days after surgery. Abdominal computed tomography revealed an incarcerated small intestine in the 8-mm port of the left abdomen, and it was diagnosed as port-site hernia incarceration. Emergency laparotomy hernia repair was performed on the day. A part of the 8-mm port was incised to 30-mm and the fascia dilatation to 30-mm was observed. The color tone of the incarcerated small intestine was good. Only adhesion peeling was performed, the small intestine was returned, and the fascia was closed. The postoperative course was uneventful and the patient was discharged 17 days after the second surgery. At the 1 year postoperative follow-up, recurrence of hernia or rectal cancer was not observed.

The recurrence of hepatocellular carcinoma(HCC)is primarily due to intrahepatic metastases. Additionally, extrahepatic HCC metastases most commonly occurs in the lungs, lymph nodes, adrenal glands, and bones. Systemic chemotherapy is the standard treatment for extrahepatic metastases. Although several reports on surgical resection of lymph node metastases (LNM) in patients with HCC have been published, its clinical benefits remain controversial. We report a case in which surgical resection of LNM was performed in a patient with HCC. The patient was a 74-year-old woman diagnosed with HCC and non-B non-C chronic hepatitis, for which she underwent a laparoscopic partial hepatectomy. The pathological diagnosis was St-A, 1.6×1.4 cm, confluent multinodular type, pT1N0M0, fStage Ⅰ. Nine months later, 2 LNM on the liver hilum were detected and managed with sorafenib. Sorafenib was discontinued after 2 months due to the development of Grade 3 hand-foot syndrome. Since no new lesions were detected on follow-up, lymph node resection was performed. The patient remains disease-free 4.5 years postoperatively.

"Arbovirus" is a term for a virus transmitted to mammals by hematophagous arthropods; arboviruses; replicate in both mammals and arthropods. Since the life cycle of arboviruses is highly dependent on arthropods, control of the arthropods (vectors) is generally considered important for the control of arbovirus infection. Various pathogens that cause diseases in the medical and veterinary fields are grouped into arboviruses with a history of their discoveries since the early 20th century. Furthermore, because of recent advances in sequencing technology, new arboviruses have been discovered one after another. Here we would like to overview the known arboviruses and their infections.

A 78-year-old woman was found to have gallbladder wall thickening on ultrasonography during a routine health check-up and was referred to our clinic. On contrast-enhanced endoscopic ultrasonography, a papillary lesion measuring 14mm was detected in the fundus, which showed a heterogeneous enhancement at the early phase. She underwent cholecystectomy and gallbladder bed resection. Histological examination revealed that the tumor consisted of mucinous atypical cells, regularly arranged in a high-papillary architecture with delicate fibrovascular cores, which led to the diagnosis of intracholecystic papillary neoplasm of the gallbladder.

Zoonoses originate from pathogens harbored in domestic and wild animals and therefore it is likely impossible to completely eradicate zoonotic diseases. For pre-emptive measures to attempt to predict the emergence of zoonosis outbreaks and the prevention of future epidemics and pandemics, it is imperative to identify natural host animals carrying potential pathogens and elucidate the routes of pathogen transmission into the human population. Our research team is conducting epidemiological research studies in Zambia and Indonesia for the control of viral zoonotic diseases. In this review, we present the research findings, including the discovery of orthopoxviruses and polyomaviruses in wildlife in Zambia and the identification of herpesviruses in bats in Indonesia among our activities.

We report a case of a large gastric gastrointestinal stromal tumor (GIST), which became resectable and achieved pathological complete response after neoadjuvant chemotherapy with imatinib mesylate. A 59-year-old man presented with left hypochondrial pain. Abdominal computed tomography (CT) revealed gastric GIST invading the spleen and the diaphragm. Administration of imatinib mesylate was initiated as neoadjuvant chemotherapy. Six months after neoadjuvant chemotherapy with imatinib mesylate, abdominal CT revealed a reduction in tumor size. We judged the tumor resectable and performed partial gastrectomy and splenectomy. Histologically, number of myofibroblasts increased, but no viable tumor cells were observed. Pathological complete response was obtained.

A 47-year-old woman underwent colectomy for advanced colon cancer and thereafter received regorafenib therapy as fourth-line chemotherapy. On treatment day 12, the patient developed erythema multiforme (EM) induced by the regorafenib therapy. Immediately after regorafenib was withdrawn, the patient was treated with oral bepotastine and steroid ointment, which relieved the EM without progressing to Stevens-Johnson syndrome (SJS). Regorafenib is used for third- or fourth-line chemotherapy. Progression of regorafenib-induced EM to SJS may cause critical dysfunction among patients. Before administering regorafenib therapy, the patient should be made aware of this potential adverse effect and be advised to withdraw the treatment and visit the hospital immediately if symptoms of EM are observed.

A 73-year-old man visited our hospital for consultation regarding a pancreatic tumor. Abdominal computed tomography, magnetic resonance imaging, and endoscopic ultrasound scan (EUS) revealed tumor 2 cm in diameter located in the pancreatic tail. EUS-guided fine needle aspiration (EUS-FNA) suggested pancreatic mixed acinar-endocrine carcinoma, and he underwent distal pancreatectomy. Few reports exist where preoperative EUS-FNA suggested pancreatic mixed acinar-endocrine carcinoma; thus, we report this case.

Recently, the family Polyomaviridae was classified as 3 genera, such as Orthopolyomavirus, Wukipolyomavirus which contain mammalian polyomaviruses and Avipolyomavirus which only contain avian polyomaviruses. We have recently isolated novel polyomaviruses, including Mastomys Polyoamvirus (MasPyV) and Vervet monkey Polyoamvirus-1 (VmPyV-1) by epidemiological activities and examined functions of their encoding proteins. In addition, we have been investigating the mechanisms of replication of human polyomavirus, JC polyomavirus (JCPyV). We recently obtained the results of function of JCVPyV-encoding proteins, including early protein (Large T antigen) and late proteins (VP1 and Agno). In this review, we summarized the data of our basic research activities.

Local recurrences often develop after the resection of bile duct cancer. Imaging modalities do not have sufficient sensitivity or specificity to enable the definite diagnosis of recurrent bile duct cancer, and it may be difficult to decide when to start chemotherapeutic treatment. It is difficult to obtain specimens by conventional endoscopy after Roux-Y biliary reconstruction. The double-balloon endoscope(DBE) has 2 balloons: one at the tip of the endoscope and the other at the over- tube. The 2 balloons are inflated alternately and the endoscope can move through the small intestine in a caterpillar-like manner. DBE simplifies the approach to Roux-Y choledochojejunostomy and to obtaining a pathological specimen. Moreover, endoscopic biliary drainage and cholangiography can be performed with the DBE. Recently, the DBE has enabled systemic chemotherapy to be started after obtaining pathological evidence of malignancy, as well as biliary drainage instead of percutaneous transhepatic biliary drainage in cases with recurrent bile duct cancers. Here, we present 3 cases of recurrent bile duct cancer diagnosed and treated by a DBE.

A 69-year-old woman who had locally advanced pancreatic cancer underwent proton beam radiotherapy(67.5 GyE/25 Fr) concurrent with gemcitabine chemotherapy (GEM 800 mg/m2 day 1, 8) at Hyogo Ion Beam Medical Center, followed by GEM chemotherapy (1,000 mg/m2 day 1, 8, 15/28 day)at Kobe University Hospital. She visited our hospital because she was suffering from dyspnea 212 days after first administration of GEM. A chest computed tomography revealed that infiltrations were spreading in the bilateral lung fields. A bronchoscopy showed diffuse alveolar hemorrhage. We diagnosed GEM related interstitial lung disease with diffuse alveolar hemorrhage. We introduced steroid pulse therapy (methylprednisolone 1 g/day) for 3 days followed by oral prednisolone (40 mg/day), which was tapered gradually. She recovered and was discharged on the 24th day after admission.

We report a case of postoperative liver metastasis arising from pancreatic carcinoma treated with a novel procedure that we developed-percutaneous isolated hepatic perfusion (PIHP). A 69-year-old man diagnosed with pancreatic body cancer(pT3, pN0, pStage III) was treated using distal pancreatectomy and adjuvant therapy with gemcitabine(GEM). Six months later, a metastasis to the medial segment of the liver was found using computer tomography(CT). The patient was treated by chemotherapy with S-1, but the liver metastasis grew, and we therefore employed PIHP as the third-line therapy, using 80 mg doxorubicin (DXR) and 62 mg mitomycin C (MMC). Six weeks after PIHP, the tumor marker carbohydrate antigen 19-9( CA19-9) had decreased from 44,469 to 4,268 U/mL, and the carcinoembryonic antigen(CEA) level decreased from 28.8 to 5.4 U/mL. Although the size of the carcinoma remained the same on CT, some cells had liquefied as a result of necrosis. However, the patient died about 1 year after PIHP due to the growth of liver metastasis, peritoneal metastasis, and local recurrence, reflected by a progressively increasing level of tumor marker. In this case, PIHP seemed to be ineffective due to local recurrence and peritoneal metastasis as well as early enlargement of liver metastasis. However, the reduction in tumor marker levels and the observed tumor necrosis, suggest that PIHP is a potentially effective and promising treatment for liver metastasis arising from pancreatic carcinoma.

Progressive multifocal leukoencephalopathy (PML) is caused by reactivation of latently infected JCV when hosts' immune system is impaired by HIV infection, hematologic diseases, collagen diseases, immunemodulatory therapy and so on. PML was rare but HIV infection and Natalizumab have made it much more common while the prognosis is much better than other PML. PML patients present with various signs and symptoms including hemiparesis, dementia, aphasia, visual disturbance, cranial nerve paresis, cerebellar signs and bladder bowel disturbance. Brain MRI reveals characteristic demyelinating lesions in the CNS white matter and CSF mild increase of protein with or without mild mononuclear pleocytosis. Detection of JCV genome from CSF is crucial for the clinical diagnosis of PML. PML was once thought to be fatal but some HIV infected PML patients showed halting progression or even recovery after introduction of HAART. In addition, anti-malarial drug mefloquine was found to be effective. Recovery of immunity may provoke some inflammatory responses known as immune reconstruction inflammatory syndrome (IRIS) which requires high dose corticosteroid. In Japan, we are providing free test of CSF-JCV genome and organized a unique system for surveillance and clinical research of PML. Using this system we hope to improve diagnosis and therapy of PML in Japan.

A 44-year-old man presented with difficulties in gripping a ball with the left hand upon playing tennis. He developed muscle weakness involving the left limbs, as well as memory decline, with subsequent gradual worsening of such symptoms. Cranial MRI showed multiple high intensity lesions in the white matter on T2-weighted imaging and FLAIR imaging. Serologic testing was positive for HIV infection and laboratory studies revealed a CD4+T cell count of 103 cells/microl and a plasma HIV-1 RNA load of 240,000 copies/ml. Accordingly, the diagnosis of AIDS was made. Although the initial result of DNA amplification by PCR for detection of the JC virus with CSF was negative, PML was suspected because of the presence of multifocal white matter lesions. Four weeks after the commencement of highly active anti-retroviral therapy (HAART), the HIV-1 RNA load was decreased from 680,000 to 480 copies/ml, although the CD4+T cell count was unchanged. JC virus DNA became positive at the second examination. Five weeks after the commencement of HAART, general fever, disturbance of consciousness, and brain edema suddenly developed, and the patient died within two days. Histological examination of the autopsied brain revealed demyelination and reactive gliosis within the white matter and JC virus antigen was detected in oligodendrocytes, consistent with a diagnosis of PML. The most striking feature was an intense perivascular infiltration by CD8+T cells with proteinaceous fluid exudation, suggesting an occurrence of HAART-induced immune reconstitution inflammatory syndrome. Immune reconstitution inflammatory syndrome should be considered as a fatal complication of HAART in patients with AIDS-related PML.

JC virus (JCV) is a causative agent of progressive multifocal leukoencephalopathy (PML) that occurs mainly in immunosuppressed patients, especially those with HIV/AIDS. JCV belongs to the Polyomavirus that are characterized by non-enveloped icosahedral capsids containing small, circular, double-stranded DNA genomes. JCV is widely distributed among the population world-wide. However, infections are usually restricted by the immune system. In this article we briefly provide an overview of the interaction between JCV and host immunity. We also review the biological and physical characteristics and the lifecycle, receptors interaction, intracellular trafficking, viral transcription and replication, progeny virus propagation of JCV to examine the pathogenicity mechanism of PML.

JC virus (JCV) is a causative agent of progressive multifocal leukoencephalopathy and belongs to Polvomavirus. In this article we describe our recent research relating to this virus. First, JCV's major capsid protein VP1 possesses a nuclear localization signal (NLS) and has the ability to construct a virus-like particle (VLP). We have investigated the mechanism of nuclear entry of JCV using VLP, and clarified the role of NLS. In vitro transport assay revealed that wild type VLP (wtVLP), but not ANLSVLP, entered the nuclei of cells. The nuclear transport of wtVLP was dependent on the addition of importins alpha and beta and was prevented by antibodies to nuclear pore complex (NPC). These results suggested that JCV VLP binds to cellular importins via the NLS of VP1 and is transported into the nucleus through the NPC. Second, a yeast two-hybrid screen of a human brain cDNA library demonstrated that the fasciculation and elongation protein zeta 1 (FEZ1) and the heterochromatin protein 1alpha (HP1alpha) are proteins that interacted with JCV agnoprotein (Agno). In vitro binding assay showed that Agno interacts directly with FEZ1 and HP1alpha. We have also shown that Agno induces the dissociation of FEZ1 from microtubules and dissociates the interaction between HP1alpha and lamin B receptor. We have demonstrated that interaction between Agno and these host proteins inhibited nuclear egress of JCV. Third, in order to inhibit JCV infection in infected cells, we synthesized siRNA which is specific for JCV Agno. Immunoblotting and immunocytochemical analysis demonstrated that expression levels of agnoprotein and VP1 were significantly inhibited by specific siRNA. In addition, levels of viral mRNAs and viral production were decreased in the cells transfected with Agno siRNA. Furthermore, viral production of cell treated with Agno siRNA was significantly inhibited. These results indicate that post-infection treatment with siRNAs, that targets JCV Agno suppresses virus production in JCV infected cells. Thus, siRNA directed against JCV encoding genes may provide a useful tool for suppression of JCV infection.

JC virus (JCV) is a causative agent of progressive multifocal leukoencephalopathy and belongs to Polyomavirus. In this article we describe our recent research relating to this virus. First, JCV's major capsid protein VP1 possesses a nuclear localization signal (NLS) and has the ability to construct a virus-like particle (VLP). We have investigated the mechanism of nuclear entry of JCV using VLP, and clarified the role of NLS. In vitro transport assay revealed that wild type VLP (wtVLP), but not deltaNLSVLP, entered the nuclei of cells. The nuclear transport of wtVLP was dependent on the addition of importins alpha and beta and was prevented by antibodies to nuclear pore complex (NPC). These results suggested that JCV VLP binds to cellular importins via the NLS of VP1 and is transported into the nucleus through the NPC. Second, a yeast two-hybrid screen of a human brain cDNA library demonstrated that the fasciculation and elongation protein zeta 1 (FEZ1) and the heterochromatin protein lalpha (HPla) are proteins that interacted with JCV agnoprotein (Agno). In vitro binding assay showed that Agno interacts directly with FEZ1 and HPlalpha. We have also shown that Agno induces the dissociation of FEZ1 from microtubules and dissociates the interaction between HPlalpha and lamin B receptor. We have demonstrated that interaction between Agno and these host proteins inhibited nuclear egress of JCV. Third, in order to inhibit JCV infection in infected cells, we synthesized siRNA which is specific for JCV Agno. Immunoblotting and immunocytochemical analysis demonstrated that expression levels of agnoprotein and VP1 were significantly inhibited by specific siRNA. In addition, levels of viral mRNAs and viral production were decreased in the cells transfected with Agno siRNA. Furthermore, viral production of cell treated with Agno siRNA was significantly inhibited. These results indicate that post-infection treatment with siRNAs, that targets JCV Agno suppresses virus production in JCV infected cells. Thus, siRNA directed against JCV encoding genes may provide a useful tool for suppression of JCV infection.

Cyclooxygenase (COX)-2 of astrocytic tumors was studied by immunohistochemistry. COX-2 was expressed in 8 of 12 (75%) glioblastoma multiforme, 1 of 7 (14%) anaplastic astrocytoma, but none in astrocytoma. COX-2 was detected by an immnoblotting in 2 of 9 human glioblastoma cell lines (KNS42 and U138). In glioblastoma cell lines, NS398 and Etodolac inhibited cell proliferation and induced apoptosis. The result showed that COX-2 expression may be related with histological grades and COX-2 inhibitors will be one of promising therapeutic tools in human astrocytic tumors.

Hemostatic abnormalities were examined in 40 patients with deep vein thrombosis (DVT), 40 patients treated with warfarin, and 30 healthy volunteers. Plasma D-dimer levels were measured by an enzyme linked fluorescent assay (ELFA; Vidas-D-dimer) and an enzyme immunosorbent assay (ELISA; D-dimer-ELISA). Plasma levels of D-dimer, thrombin-antithrombin complex (TAT), soluble fibrin monomer (SFM) were significantly higher in patients with DVT than in the other groups. Both the sensitivity and specificity of D-dimer for diagnosis of DVT were the highest among hemostatic molecular markers examined. The most adequate cut off value of Vidas-D-dimer was 0.6 microgram/ml. Plasma levels of Vidas-D-dimer were well correlated with D-dimer ELISA, SFM and TAT. As the time of measurement for Vidas-D-dimer is less than one hour, the measurement of D-dimer using a EFLA might be useful for the diagnosis of DVT in bed side.

We report a case of a patient with primary cerebral neuroblastoma who has survived for 8 years. A 10-year-old boy was admitted to our hospital because of headache and nausea. CT scan on admission revealed a large cystic tumor on the right frontal lobe. Subtotal tumor resection was carried out. A second operation was performed for the residual tumors which were removed meticulously with confirmation of the absence of tumor cells on each frozen section. After tumor removal, YAG laser was applied at each local area. Histological diagnosis disclosed primary cerebral neuroblastoma. Because of postsurgical meningitis and parent's refusal, neither chemotherapy nor radiation therapy was performed. There have been no findings of the tumor recurrence during the last eight years, and now the patient is enjoying high school life to the full, without any neurological deficits. In reviewing the literature, outcomes of neuroblastoma cases are very poor. Our case seems to be one of the rare long-survival cases.

Object: To compare the results of vitrectomy for phakic cases and those of aphakic cases with proliferative diabetic retinopathy (PDR) accompanied by rubeosis iridis., Materials & Methods: We reviewed 34 eyes of 24 cases that underwent vitrectomy for proliferative diabetic retinopathy with rubeosis iridis., Result: Phakic eyes needed significantly more reoperations (p < 0.001) than aphakic eyes. Aphakic eyes had significantly more successful visual results (p < 0.05) and better control of intraocular pressure (p < 0.005) than phakic eyes., Conclusion: This study showed the possibility that phakic eyes had more ischemic retina producing more angiogenic factors than aphakic eyes which had the same grade of rubeosis iridis. Phakic eyes with pre-operative rubeosis iridis need thorough clearance of ocular ischemia by panretinal photocoagulation.

Vitreous hemorrhage recurred in 11 eyes out of a series of 120 eyes treated by vitrectomy for proliferative diabetic retinopathy during a 10-month period. Neovascularization from the scleral wound, or fibrovascular proliferation, was identified as the cause of rebleeding in 4 eyes from findings during revitrectomy. None of the 4 eyes showed retinal disorders attributable as the cause of rebleeding. Rebleeding in these 4 eyes developed after an average of 9.0 weeks after initial surgery. The proliferative membrane was oval in shape and expanded from the residual vitreous which had been incarcerated in the scleral wound. The proliferative membrane obtained during revitrectomy was poor in cellular components and contained extracellular matrix. Blood vessels of various sizes were also present. Electron microscopically, the membrane was rich in extracellular components. It contained two types of cells, i.e., high and low electron density cells. These cells often had microvilli and seemed to be of epithelial origin. The findings show that vitreous rebleeding may develop from fibrovascular proliferation from the scleral wound after diabetic vitrectomy. The proliferated membrane showed histological similarities with the fibrovascular proliferation usually seen in the diabetic retina and may represent a type of anterior proliferation secondary to retinal ischemia.

Gene expression of HGF and c-met proto-oncogene was examined during rat brain development and in cultured PC-12 cells, using reverse-transcriptase (RT)-polymerase chain reaction (PCR) technique. The both mRNAs of HGF and c-met proto-oncogene were remained at low levels in the middle and late stages of gestation (E-13 and E-18). After birth, and the level of both mRNA expression suddenly increased. During P-1 and P-12, their high level of expression continued and then decreased in P-20 and adult brain. Both HGF mRNA and c-met photo-oncogene mRNA were transiently expressed between day 2 and day 5, and disappeared in cultured PC-12 cells treated with NGF. The neurites of PC-12 cells that were treated with anti-sense oligonucleotides of HGF and c-met proto-oncogene, were shorter and fewer in number than untreated control cells. We conclude that neurite extension of PC-12 cells treated with NGF may ensue by way of c-MET protein activation and signal transduction pathways. Thus, c-MET protein activation and up-regulation of the two mRNAs may also play an important role in neuronal maturation in the developing rat brain.

An anonymous questionnaire survey was conducted among persons who had undergone screening for AIDS at public health centers under the auspices of 7 local government bodies (Hokkaido, Metropolitan Tokyo, Aichi Prefecture, Osaka Prefecture, Kobe City, Saga Prefecture, Okinawa Prefecture). There were 1,230 replies, for a response rate of 46.8%. Questions in the survey pertained to general knowledge of AIDS, information desired by the recipients, desired ways to foster awareness, and a desirable examination system. A comparison was made in terms of gender, marriage status (married, single) and age (less than 40 years of age, more than 40 years of age), respectively. The survey results were as follows. 1. Concerning the infection route, accurate response rate was low with regard to the mother-child infection, mosquito transmission, and use of contaminated needles. 2. Desired methods to promote AIDS awareness expressed among replies were given in the following order or frequency: "information via radio and TV," "spread of knowledge through telephone consultation," and "holding an AIDS Week or similar kinds of campaigns." 3. Information sought by respondents frequently included AIDS treatment, pathology, and spread. This trend was most obvious among those under 40 years of age. 4. As for the AIDS examination system, replies most often reflected the hope that the examination site would be the Public Health Center, the charge would be gratis, and that one could be examined at night during the week, and on days off. 5. For those undergoing examination where there was no actual concern of possibility of HIV infection, single persons, accounted for around 80% of the overall. 6. More than half of those who had been examined mentioned having experienced concerns about maintaining confidentiality at the time they were examined.

To determine whether HTLV-I infection is associated with uveitis, we investigated the bronchoalveolar lavage fluid (BALF) cells in 23 patients with uveitis. Of these, sarcoidosis was diagnosed in 13 patients, but could not be confirmed in the remaining 10 patients (non-sarcoidosis). Three of 13 patients (23.1%) with sarcoidosis and 7 of 10 non-sarcoidosis patients (70.0%) were HTLV-I seropositive. In BALF, no significant differences were observed between the HTLV-I seropositive and seronegative patients. However, in non-sarcoidosis patients, total cell counts, CD3+ and CD+ HLA-DR+ cells in BALF were significantly higher in seropositive patients than in seronegative patients. CD3+ CD25+ cells in BALF were markedly increased in 3 of 7 non-sarcoidosis seronegative patients. These findings indicated that BALF lymphocytes in HTLV-I seropositive non-sarcoidosis patients were more activated than those in seronegative non-sarcoidosis patients, supporting the hypothesis that HTLV-I infection may be associated with uveitis.

The mechanisms of erythromycin (EM) in chronic lower respiratory tract diseases including diffuse panbronchiolitis (DPB) has been reported. In this study we investigated the effect of EM on peripheral neutrophil adhesion molecules such as LFA-1 and Mac-1 obtained from six healthy subjects. Pretreatment of neutrophils with each concentration (10 ng/ml approximately 100 micrograms/ml) of EM resulted in no significant reduction in the expression of LFA-1 alpha, beta and Mac-1. Moreover, EM had no capability of reducing these expressions even when neutrophils were pretreated with 1 microgram/ml of EM at time from 0 to 60 min. These findings indicate that EM does not directly reduce the expression of LFA-1 alpha, beta and Mac-1 on peripheral neutrophil obtained from healthy subjects.

p53 gene which is known as a tumor suppressor gene locates in chromosome 17p and has a polymorphism at codon 72 (Arginine CGC-->Proline CCC). In this study, we examined the frequency of polymorphism and of heterozygosity in Japanese, and the loss of p53 gene in brain tumor tissues of the patients with heterozygosity using a novel method. The frequencies of heterozygosity, arginine type, proline type were 43%, 42% and 15%, respectively. Heterozygosity was observed in 15 out of 32 patients with brain tumors and loss of heterozygosity (LOH) in these 15 cases was demonstrated in 40%. Although we are not certain whether LOH of p53 region is inevitable process of oncogenesis of some brain tumors, some false negative results may occur. This quick technique requires small amount of samples and no radioactive isotope, therefore, can be applied to detect mutation and LOH occurred in p53 region in terms of the genesis and progression of human neoplasms.

It is well known that erythromycin (EM) therapy is effective on chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB). In this study we investigated the relationship between clinical findings and neutrophil chemotactic activity (NCA) in bronchoalveolar lavage fluid (BALF) in patients with DPB receiving orally EM therapy. The NCA in post-EM therapy BALF was significantly reduced (p less than 0.001) compared with that in BALF before EM therapy (30.17 +/- 7.84% vs 53.05 +/- 10.65%). On the respiratory function before and after EM therapy, DPB patients (20 cases) showed significant improvement of %VC, FEV1.0, RV/TLC (p less than 0.001, each) and V25 (p less than 0.05). And on the post-EM therapy blood gas, PaO2 and AaDO2 level were confirmed to be significantly improved (p less than 0.001). In addition, we examined the correlation between the improvement ratio of clinical finding and the reduction of NCA in BALF after EM therapy in 10 patients with DPB. We found the significant correlation between the improvement ratio of PaO2 and the reduction NCA in BALF of those patients (p less than 0.05). There were no significant relationships between the improvement ratio in other parameters as stated above and the reduction of NCA in BALF. These findings indicate that EM restrains the NCA in BALF of patients with DPB and impairs the accumulation of neutrophils in respiratory tract, ultimately contributes to the improvement of clinical symptoms such as sputum and clinical findings such as PaO2 in patients with DPB.

As one of the fundamental studies of the pre-operative chemotherapeutic methods in 22 cases with colonic cancer, we studied a progress of the concentration in blood and concentration in tissues including those in the portal vein after administration of UFT. The concentration of 5-FU in blood reached to the peak at 2 hours after administration of UFT and then decreased rapidly, while it was maintained for a long term in comparing with that of 5-FU (oral remedies; tablet and dry syrup). This fact suggested that UFT can be expected for metastatic inhibition and prevention of the recurrence because it showed an effect in free-cancerous cells before and during operation. The anti-tumorous effect was also expected because the concentration of 5-FU in cancerous tissues was significantly higher than that in non-cancerous region. In our study in this time, down staging was considered by pre-operative chemotherapeutic method of colonic cancer in the future because concentration of 5-FU was also highly obtained in metastatic lymph nodes. From the above-mentioned results, pre-operative chemotherapeutic method using UFT was expected as a part of the intensive therapies.

The "low dose and long term" erythromycin (EM) therapy has been reported as effective (or useful) in chronic respiratory tract disease with pseudomonas (P.) infection including diffuse panbronchiolitis (DPB), however the mode of action is still obscure. Therefore in this study we have examined the effect of EM on the interaction between P. aeruginosa and human polymorphonuclear leukocyte (PMN) in vitro. The efficiency of intracellular killing and the ability of superoxide production were employed to evaluate the PMN functions. For the first step, the following results were obtained; 1) Pretreatment of PMN with 20 micrograms/ml EM did not affect the killing ability of PMNs against opsonized P. aeruginosa of standard and clinical isolate from DPB patient. 2) Superoxide production from PMNs was observed by phagocytosis of P. aeruginosa in the presence of serum. This was not affected by exposure of PMNs to 20 micrograms/ml EM even with increased ratios of bacteria to cells. 3) Pretreatment of P. aeruginosa with 20 micrograms/ml EM before opsonization enhanced the killing ability of PMNs in both standard and clinical isolate. 4) Pretreatment of P. aeruginosa with 20 micrograms/ml EM resulted in no effect on superoxide production from PMNs by phagocytosis of the bacteria. These results indicate that EM may modify a certain step of the interaction between bacteria and intracellular host defence mechanisms. Therefore for the second step, we have investigated the susceptibility of EM-exposed bacteria to killing by the cell free (glucose oxidase-glucose) system, which will detect the enzymatic generation of hydrogen peroxide (H2O2). The following results were observed; 1) EM-exposed bacteria was more susceptible to killing than control bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen, the precursor of the biologically active peptide angiotensin II, is known to be synthesized in the liver and to be localized in plasma, constituting the circulating renin-angiotensin (R-A) system. Recent animal studies have provided evidence for the local generation of angiotensinogen within tissues, independently of the circulating R-A system. To determine the sites of angiotensinogen synthesis in human tissues, we tested for the presence of angiotensinogen and its mRNA in various organs. Messenger RNAs extracted from the liver, kidneys, heart, and brain were all hybridized with human-angiotensinogen complementary DNA. By using a monoclonal antibody generated by in vitro immunization of spleen cells with the synthetic peptide, we first confirmed that the antibody detected only angiotensinogen on immunoblots. In immunohistochemical studies, intense immunoreactivity was found in atrial muscle and in the muscle fibers of the conduction system. The ventricular working myocytes were not stained. Less intense staining was observed in the glomerular tufts of the kidneys, in a few hepatocytes and Kupffer cells, and in the bile duct epithelium of the liver. Thus we demonstrated that angiotensinogen is also synthesized in extrahepatic tissues, including the heart, and that it is localized mainly in the specific cells of the heart. This suggests that the tissue R-A system plays an important role in the human heart.

Since 1981, cancer has been No. 1 cause of death in Japan. A "Comprehensive 10-Year Strategy for Cancer Control" is a national project that was strongly promoted by the former Prime Minister Mr. Yasuhiro Nakasone in 1983. The program comprises project research studies and functions supporting them. These include the education and utilization of young researchers (research resident), international cooperation and research resources (cell and gene) bank. The aim of studies is clarification of the mechanism of human carcinogenesis within 10 years and the results will be applied to prevention, diagnosis and therapy of cancers.

A case of central pontine myelinolysis (CPM) following rapid correction of hyponatremia was reported and literatures were reviewed. The case was 61-year-old nonalcoholic female who had taken an operation of craniopharyngioma 23 years ago. Fifteen years later, she received re-operation for the recurrent tumor, followed by replacement therapy of corticosteroid and clofibrate. She was otherwise well until two weeks before entry, when she noticed abrupt onset of high grade fever, nausea, vomiting and general malaise. She was admitted to an emergency hospital because of weakness, disorientation and a slight impairment of consciousness, but she was able to speak and to take some food per os. Laboratory studies disclosed urinary tract infection and showed a serum sodium level of 117 mEq/l, potassium 2.9 mEq/l, a serum osmolarity 232 mO sm/l and urine osmolarity 141 mEq/l. She was diagnosed to have an exacerbation of adrenal insufficiency with hyponatremia and hypotonic dehydration triggered by urinary tract infection. Intravenous administration of vitamin B complex, electrolytes including KCL, 5% glucose solution and physiological saline with a large amount of corticosteroid was performed aggressively. Serum sodium concentration was raised to 161 mEq/l in two days, and the increased level had been maintained more than five days, resulting in coma and flaccid quadriplegia. During this period, there was no episode of hypotension, hypoglycemia, hypoxia nor hepatic failure which could have caused brain damage.(ABSTRACT TRUNCATED AT 250 WORDS)

A 67-year-old male was admitted to our clinic on May 1, 1981, because of mild confusion and a left hemiparesis. About 6 years ago, when he had a left-sided homonymous hemianopia, carotid angiography revealed moyamoya disease. CT scan on the admission showed an intracerebral hematoma in the right temporal lobe, which ruptured to the lateral ventricle. An angiogram demonstrated the net work of moyamoya vessels in the base of the brain and a "newly-appeared" aneurysm at the peripheral portion of the right anterior choroidal artery. This artery was shown on the previous angiogram also but did not bear the aneurysm. At the emergent operation the hematoma was evacuated and the aneurysm was excised, which was proved histologically to be a false aneurysm. Thirty-six cases of moyamoya diseases associated with aneurysm including the present case were reviewed. There were 44 aneurysms in this series. They were classified into groups--1) the major artery aneurysms arising from the major cerebral arterial segments; 2) the peripheral artery aneurysms arising from the distal segments of the peripheral cerebral arteries. The major artery aneurysms were found more frequently in the vertebro-basilar system, and the peripheral artery aneurysms in the basal ganglia, near or in the moyamoya vessels. Of 26 major artery aneurysms 12 were proved to be saccular aneurysms, 9 by surgeries and 3 by autopsy studies respectively. Of 18 cases of the peripheral group the aneurysms were excised operatively in two cases, and autopsy studies were performed in other two cases. The peripheral artery aneurysms were examined histologically in three cases; one was proved to be a false aneurysm, the other was thought to be a true aneurysm, and the third one was not verified. In 8 cases, the peripheral artery aneurysms disappeared on the follow-up angiograms and were supposed to be false aneurysms. From these reported cases, it may be suggested that major artery aneurysms are mainly true aneurysms and peripheral artery aneurysms are false aneurysms.