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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 361 records · Page 20Linked to original sources

Involvement of IMP dehydrogenase activity in induction of sporulation of Bacillus cereus.

IMP dehydrogenase activity of B. cereus increased parallel to cell growth in YE-EMM, where B. cereus did not sporulate. When B. cereus was cultured in a modified G medium, a sporulation medium, the activity reached the highest level at 6 hr and decreased thereafter. After induction of sporulation by nutritional shift down in 1/100 G medium, the enzyme activity decreased to about 5% compared with exponentially growing cells at 1 hr of resuspension. The sporulation rate of B. cereus was over 90% in the modified G medium and 1/100 G medium. Sporulation was strongly inhibited by mycophenolic acid at 1 mM, when the drug was added at 0 and 1 hr of resuspension in 1/100 G medium. Intracellular GTP concentration of B. cereus decreased to the lowest level about 1 hr of resuspension. Although GTP increased to about 50% of the exponentially growing cells at 2 hr of resuspension in control cells, the concentration did not increase in the presence of 1 mM mycophenolic acid.

Bacillus cereus↗

A phase I/II study of a hypoxic cell radiosensitizer KU-2285 in combination with intraoperative radiotherapy.

A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given before intraoperative radiotherapy (IORT) to 30 patients with unresectable, unresected or macroscopic residual tumours. Twenty-three patients had pancreatic cancer and five had osteosarcoma. The IORT dose was 30 Gy for unresectable pancreatic cancer and 60 Gy for osteosarcoma. The dose of KU-2285 administered ranged from 1 to 9 g m-2. Four patients received a dose of 9 g m-2, and ten received 6.8-7 g m-2. All patients tolerated KU-2285 well, and no drug-related toxicity was observed. The average tumour concentration of KU-2285 immediately after IORT was 166 microg g-1 at dose of 6.8-7 g m-2 and 333 microg g-1 at 9 g m-2. The average tumour-plasma ratio was > or = 0.82. Eleven patients with unresectable but localized pancreatic cancer treated with KU-2285 plus IORT and external beam radiotherapy had a median survival time of 11 months and 1-year local control rate of 50%, which compares favourably with those of 8 months (P = 0.26) and 28% (P = 0.10) for 22 matched historical control patients. The five patients with osteosarcoma attained local control. The results of this first study on KU-2285 and IORT appear encouraging, and further studies of this compound seem to be warranted.

Adolescent↗

The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-versus-host disease.

We have investigated cytokine mRNA expression in the peripheral blood mononuclear cells of 20 patients who received allogeneic hematopoietic stem cell transplants to assess the cytokine network after transplantation. IL-4 mRNA expression decreased in five of five (100%) patients with > or = grade III (severe) acute GVHD and increased in 10 of 22 (45%) patients without severe GVHD. In contrast, IL-12 mRNA expression increased in two of two (100%) patients with severe GVHD, but increased in only six of 18 (33%) patients without severe GVHD. Furthermore, IL-10 and/or IL-13 mRNA expression increased in 19 of 22 (86%) patients without severe GVHD, but increased in only one of three (33%) patients with severe GVHD. In patients with allogeneic PBSCT who had severe acute GVHD, the cytokine mRNA expression in patients with allogeneic PBSCT, who had no severe GVHD, showed a similar pattern to that in patients with allogeneic BMT. IL-4 mRNA expression increased in three of five (60%) patients and IL-10 and/or IL-13 mRNA expression increased in five of five (100%) patients. In contrast, IL-12 mRNA expression increased in only one of three (33%) patients. Serum IL-4 concentration in allogeneic PBSCT patients in the early engraftment phase was relatively high, while serum IL-12 concentration was low. These findings suggest that severe GVHD may be related to the cytokine imbalance between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells.

Adult↗

Inhaled vancomycin-induced allergic reaction in decontamination of respiratory tracts for allogeneic bone marrow transplantation.

A 34-year-old male suffered from an allergic reaction after inhalation of decontaminating drugs for BMT. Clinical challenge tests were undertaken to determine the causal drug. It was found that vancomycin hydrochloride (VCM) repeatedly induced dyspnea, fever, hypoxia, eosinophilia, and elevation of CRP. Therefore, clindamycin (CLDM) was used instead of VCM for decontamination of patient respiratory tract. Although complete decontamination of the respiratory tract was not achieved during the leukocytopenic period, BMT was successful, and there were no life-threatening infectious complications. Although inhaled VCM-induced allergic reaction may be a very rare complication in the BMT setting, careful clinical attention should be paid to such patients.

Administration, Inhalation↗

Mechanism of the negative inotropic effect of midazolam and diazepam in cultured foetal mouse cardiac myocytes.

We have investigated the effects of midazolam and diazepam on intracellular calcium (Ca2+) handling in foetal mouse ventricular myocytes using the Ca(2+)-sensitive fluorescent indicator, indo-1. We also investigated separately whether flumazenil or the L-type Ca2+ channel agonist, Bay K8644, antagonized these myocardial depressive effects. Midazolam and diazepam decreased the Ca2+ transient and beating rate in a concentration-dependent manner, and these decreases were prevented by Bay K8644. Flumazenil did not antagonize the myocardial depressive effects. In myocytes whose sarcoplasmic reticulum was inhibited by ryanodine, midazolam and diazepam had the same potent cardiodepressive effects. Midazolam and diazepam are direct cardiac depressants, which decrease the Ca2+ transient and beating rate, and the L-type Ca2+ channel is important in the negative inotropism and chronotropism caused by these drugs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Preferential localization of human CD5+ B cells in the peritoneal cavity.

In a transgenic mouse model of autoimmune haemolytic anaemia, CD5+ B lymphocytes localized in the peritoneal cavity are shown to play an important role in the onset of autoimmune disease. The authors have examined whether CD5+ B cells are present in the peritoneal cavity of 12 human individuals with non-invasive gastrointestinal tumours and found that in humans CD5+ B cells preferentially lodge in the peritoneal cavity as compared to the peripheral blood and spleen while the numbers of the peritoneal B lymphocytes in humans are much lower than in mice and vary widely between individuals.

Animals↗

Genetic alterations in patients with esophageal cancer with short- and long-term survival rates after curative esophagectomy.

OBJECTIVE: The objective of this study was to ascertain the exact relation between specific oncogenes and long- and short-term survival rates in patients with esophageal cancer. SUMMARY BACKGROUND DATA: Recent developments in molecular biology have shown that several oncogenes and suppressor genes are involved in the development of esophageal cancer. However, the role of these genes still is unknown. METHODS: The clinical outcome of 84 cases of R0-resected esophageal carcinomas (from 1986-1993) and the molecular and biologic characteristics of these tumors were studied. The patients studied were divided into three groups, which were designated as follows: shortest term survivors (up to 6 months), short-term survivors (7-12 months), and long-term survivors (>5 years). These groups included 23, 17, and 44 subjects, respectively. For the genomic analysis, CyclinD1, int-2, murine double minute 2 (MDM2), retinoblastoma, p53, adenomatous polyposis coli (APC), deleted in colorectal carcinoma (DCC), and human papillomavirus were studied in these patients. The regrowth capability of primary cultures and the clinicopathologic characteristics of these patients also were analyzed. RESULTS: The CyclinD1 and int-2 genes, which are located in the 11q13 chromosome, and the MDM2 gene were related to short survival. However, the p53 mutation and human papillomavirus infection were not related to short-term survival. The average ratio of genomic abnormalities to genes examined was higher in the shortest and short-term survival groups than in the long-term survival group. Regrowth capability in primary cultures also was related to short-term survival. Among the long-term survival patients, 7 (16%) of 44 cases suffered further cancer after esophagectomy. CONCLUSIONS: These results suggest that the 11q13 amplicon and MDM2 may play an important role in the progression of esophageal cancer, and an accumulation of genomic abnormalities may result in poor prognosis. Careful follow-up testing for double cancer is needed in long-term survivors of esophageal cancer.

Chromosome Aberrations↗

5-Fluorouracil + cisplatin + mitomycin C is a relatively most effective combination against xenograft lines of human colorectal cancer.

5-Fluorouracil (5-FU) has been an accepted effective against colorectal cancer, but combination regimens resulted in a lesser effect than 5-FU alone. The present study was designed to evaluate the efficiency of various combination chemotherapies, including 5-FU, on human colorectal cancer xenograft lines (CC-KK and RC-TK), which had been passed by transplantation in nude mice. Eight anticancer agents [5-FU, mitomycin C (MMC), adriamycin (ADR), 4'-epirubicin (EPIR), carboquone (CQ), cisplatin, carboplatin and etoposide (VP-16)] and their combinations were evaluated at 2-4 times the clinical dose. When the agents were administered singly, 5-FU, EPIR and CQ were effective against CC-KK, and 5-FU, MMC, EPIR, ADR, CQ and carboplatin were effective against RC-TK. Of the two-agent combinations including 5-FU, cisplatin + 5-FU was the most effective against both CC-KK and RC-TK. However, of the three-agent combinations, only cisplatin + 5-FU + MMC was more effective against both lines than cisplatin + 5-FU. These results suggest that cisplatin + 5-FU + MMC may be the most useful regimen against colorectal cancers in clinical application.

Adenocarcinoma↗

Role of apoptosis in duct obstruction-induced pancreatic involution in rats.

It has been recognized in mammals that after pancreatic duct obstruction, acinar cells progressively disappear and pancreatic islets are preserved. Previous studies by electron microscopy have suggested the involvement of apoptosis in acinar cell deletion. In the present study, we employed molecular biological methods and investigated whether acinar cell deletion is due to apoptosis. In male Sprague-Dawley rats, pancreatic duct ligation was performed through a left paramedian incision. Pancreatic tissue was studied at each of the following intervals after ligation: 3, 6, 12, 18, and 24 h and 2, 3, 5, and 7 days. DNA fragmentation was determined by in situ labeling of DNA strand breaks on tissue sections [fluorescein-labeled terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method (TUNEL)] and by electrophoretic detection of the fragments of extracted DNA. Tissue sections were also examined by hematoxylin/eosin staining and immunohistochemical staining of insulin. Pancreatic duct ligation induced acinar cell deletion by day 5. Pancreatic tissue from control rats demonstrated no TUNEL-positive nuclei. In contrast, acinar cells from rats 12 h to 5 days after duct ligation showed TUNEL-positive nuclei. The number of TUNEL-positive nuclei was maximum 2 days after duct ligation. Electrophoresis showed DNA fragmentation after duct ligation. Control rats showed a genomic DNA pattern. Islets were preserved throughout the experimental period in duct-ligated rats and control rats. The results suggest that apoptosis may be the dominant form of acinar cell death in the rat pancreatic duct ligation model.

Amylases↗

Expression of Bcl-2 and PCNA in duct cells after pancreatic duct ligation in rats.

Obstruction of the pancreatic duct induces acinar cell deletion followed by duct proliferation and interstitial fibrosis. Apoptosis has been reported to be involved in the induction of acinar cell deletion after pancreatic duct ligation (PDL) in rats, however, the mechanism of pancreatic duct cell proliferation is still unknown. We hypothesized that Bcl-2 (antiapoptosis protein) and PCNA (cell cycle-related protein) could be involved in the mechanism of pancreatic duct cell proliferation after PDL. In PDL, rats, acinar cells decreased in number and disappeared completely after duct ligation and duct-lining cells increased in number and formed duct-tubular complexes. Immunohistochemical study showed that PCNA expression appeared in the ductules and centroacinar cells from early stages after duct ligation and that Bcl-2 expression in duct cells, which was faint in normal pancreas, increased significantly when acinar cells were diminishing. Western blotting demonstrated that Bcl-2 was detected as a single band at 26 kDa, and the intensity of Bcl-2 in PDL rats was approximately ninefold stronger than in normal pancreas. Expression of Bcl-2 and PCNA after pancreatic duct ligation may be related to the prevention of apoptosis and cell proliferation of pancreatic duct cells in rats.

Animals↗

Clinical significance of serum p53 antigen in patients with pancreatic carcinomas.

BACKGROUND: Alterations in the p53 gene are often found in pancreatic cancer, and accumulation of the p53 protein has been noted in tumour cells. AIMS: To investigate whether serum p53 protein concentrations could be used as markers for p53 gene mutations in neoplasms of the pancreas. METHODS: Serum p53 protein concentrations were determined by an enzyme linked immunosorbent assay (ELISA) in 104 cases of pancreatic adenocarcinoma, and 61 matched formalin fixed tissue sections were also stained by an anti-p53 DO-7 monoclonal antibody. RESULTS: The mean serum concentration of p53 protein in the adenocarcinoma patients was 0.27 (SEM 0.02) ng/ml, and was significantly higher than in 35 healthy blood donors (0.15 (0.02) ng/ml, SD = 0.11) or in 15 cases of chronic pancreatitis (0.15 (0.02) ng/ml). Adopting an arbitrary cut off value for the serum p53 protein concentration of 0.37 ng/ml, which corresponded to a value 2 SD above the mean value from the healthy blood donors, positive serum p53 protein concentrations were found in 23 out of 104 (22.1%) patients with adenocarcinomas examined, 16 out of 47 (34.0%) patients with carcinomas with distant metastases, but only seven of 57 patients (12.3%) with carcinomas without metastases (p < 0.05). In 11 patients with pancreatic adenocarcinomas, the mean serum p53 protein concentration after tumour resection was 0.21 (0.05) ng/ml, and had decreased compared with the preoperative concentrations (0.25 (0.05) ng/ml) (P < 0.05). There were no significant associations between the serum concentrations of p53 protein and serum concentrations of markers such as CA19-9 or CEA; however, serum concentrations of p53 protein demonstrated a potential role as an additional tumour marker. Immunohistochemical studies disclosed that the p53 protein was expressed in 28 out of 61 pancreatic adenocarcinomas (45.9%). Serum p53 protein concentrations in the positively immunostained cases were significantly higher than in the negatively immunostained cases (0.35 (0.05) ng/ml v 0.15 (0.01) ng/ml; p < 0.005). Furthermore, positive immunostaining for p53 protein was found in eight out of 10 (80%) serum positive p53 protein cases with adenocarcinomas. CONCLUSION: An increase in serum p53 protein concentrations appears during the progression of pancreatic adenocarcinoma and correlates with the accumulation of p53 protein as a result of a mutation of the p53 gene. An analysis of p53 antigen concentrations can detect p53 gene alterations, which could be useful for the selection of treatment regimens.

Adenocarcinoma↗

Role of neutrophils in cerulein-induced pancreatitis in rats: possible involvement of apoptosis.

We investigated the role of neutrophils and the involvement of apoptosis in cerulein-induced acute pancreatitis. Male Sprague-Dawley rats were divided into 2 groups. In the control group, acute pancreatitis was induced by subcutaneous injections of cerulein. In methotrexate-treated group, the rats received intraperitoneal injections of methotrexate to produce neutrophil depletion before the injections of cerulein. The rats were sacrificed at the indicated time points until 72 h after the first injection of cerulein. Neutrophil depletion ameliorated pancreatic edema and vacuole formation in acinar cells during the early stages of cerulein-induced acute pancreatitis. Electron microscopy, DNA gel electrophoresis and in situ nick end-labeling revealed the involvement of apoptosis in acinar cells in cerulein-induced acute pancreatitis. Furthermore, the number of apoptotic acinar cells in neutrophil-depleted rats showed an about 2-fold increase during the late stages when compared with those in the control rats. Our results suggest that neutrophil depletion in cerulein-induced pancreatitis leads to amelioration of pancreatic injury during the early stage, and enhancement of apoptosis by neutrophil depletion occurs during the late stage.

Acute Disease↗

Invasive pulmonary aspergillosis complicated by subclavian artery occlusion following allogeneic stem cell transplantation.

We describe an unusual case of invasive pulmonary aspergillosis (IPA) complicated by subclavian artery occlusion in a 32-year-old man with severe aplastic anemia, who underwent allogeneic stem cell transplantation. He was severely neutropenic after the conditioning for transplantation, but he had no history of fungal infection. Five days after the transplantation, he developed IPA in the left upper lung, complicated by left subclavian artery occlusion. Extensive chronic graft-versus-host disease, which required the administration of potent immunosuppressants for a long period of time, interfered with the resolution of the IPA.

Adult↗

Clinicopathologic study of leptomeningeal carcinomatosis involving the temporal bone.

The temporal bone pathology of a 71-year-old man with bilateral sensorineural hearing loss and facial paralysis caused by diffuse metastatic leptomeningeal carcinomatosis is described. The origin of this malignant disease was an extremely rare entity, a transitional cell carcinoma of the renal pelvis. Histopathologic study of the temporal bone demonstrated that tumor cells filled the internal auditory meatus, infiltrated into the Rosenthal's canals, and reached the scala tympani of the basal turn of the bilateral cochleas. The vestibulocochlear nerve and facial nerve trunks in the internal auditory meatus had been destroyed by the bilateral tumor invasion. Case reports of temporal bone metastases of leptomeningeal carcinomatosis published since 1965 were reviewed. In leptomeningeal carcinomatosis, it is suggested that tumor cells infiltrate the internal auditory meatus of both ears simultaneously from the cerebrospinal fluid, involving the seventh and eighth nerve trunks, and then cause bilateral sensorineural hearing loss and facial paralysis.

Aged↗

Clinical observations on acute low-tone sensorineural hearing loss. Survey and analysis of 137 patients.

We retrospectively analyzed the clinical records of 137 patients who were treated at our clinic for acute low-tone sensorineural hearing loss of unknown cause over a period of 8 years. The analyses of the clinical records indicated the following clinical characteristics: female preponderance; peak incidence during the fourth decade of life; frequent accompanying tinnitus, sensation of ear fullness, and/ or autophony; suspicion of bilateral involvement; and association with autonomic imbalance. The hearing in most of the patients completely recovered, but some selected patients experienced fluctuating hearing loss or progression to Meniere's disease. Our results suggest that a subgroup of patients with severe initial hearing loss should be carefully followed up, although it is difficult to predict the outcome of this disorder.

Acute Disease↗