Successful treatment of metastatic skin lesions with electrochemotherapy.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to N Aoyama.
Explore the source record for details and available documents.
BACKGROUND: Although alpha-adrenergic blockers are widely used as a treatment of benign prostatic hyperplasia (BPH), it is not clear whether contractile property of hyperplastic prostate to alpha-adrenergic agonist depends upon an area of density of smooth muscle within the respective BPH tissue. METHODS: Functional study and quantitative morphometric analysis were performed on human prostatic specimens obtained by transurethral resection from 22 men with symptomatic BPH. Tissue norepinephrine content was also evaluated. RESULTS: There was a linear correlation between the area of density of smooth muscle and maximum response to phenylephrine (r = 0.457, P = 0.0362). Although the area of density of smooth muscle showed a positive correlation with norepinephrine content (r = 0.437, P = 0.0471), norepinephrine content was not correlated with maximum phenylephrine response. CONCLUSIONS: Contractile response to alpha-adrenergic agonist was directly influenced by the area of density of the smooth muscle within an individual prostate.
Cerebrovascular damages leading to subsequent reductions in regional cerebral blood flow (rCBF) may play an important role in secondary cell damages following traumatic brain injury (TBI). Recent studies have demonstrated that rCBF markedly decrease in experimental model of TBI (e.g. fluid percussion injury, acute subdural hematoma, contusion). However, precise mechanisms underlying post-traumatic CBF reduction remain unclear. In the present study, the rCBF changes and microthrombosis formation were investigated in a cortical contusional model in rats, and the effects of etizolam (platelet activating factor antagonist) on microthrombosis were tested. The rCBF in the peripheral areas increased transiently, and decreased to ischemic level 3 hours post- injury. The histological examinations revealed microthrombosis formation in the contused area, extending from the center to the peripheral areas within 6 hours post-injury. The rCBF decrease and the contusion necrosis volume were significantly attenuated by etizolam administration. These results indicate that platelet activating factor is involved in microthrombosis formation and hemodynamic depression, and resultant ischemic damages within areas surrounding the contusion.
Oxygen free radicals may contribute to tissue injury processes in the central nervous system following ischemia or trauma. Recent studies have suggested that inhibition of free radicals improves the outcome in experimental models involving such conditions, and antioxidant therapy appears promising. In the present study, behavioral changes and edema formation in rat cortical contusion model were investigated, and the effects of a superoxide radical scavenger, OPC-14117, were tested. Wistar rats were anesthetized with halothane inhalation. Cortical contusion was induced in the parietal cortex employing a controlled cortical impact device. Immediately following injury induction, OPC-14117 was administered (300 mg/kg, p.o.). Edema formation was assessed in the center and peripheral areas of the contusion by the specific gravity method. Behavioral changes were evaluated by the Morris water maze test and the habituation of exploratory activity. The results revealed that the vehicle-administered control showed progressive edema formation and behavioral deficits following the injury. These changes were significantly attenuated by the OPC-14117 treatment (p < 0.05). Further, OPC-14117 reduced the size of contusional necrosis (p < 0.05). These findings suggest that superoxide free radicals are involved in contusion-induced edema formation, necrosis formation, and behavioral deficits, and that OPC-14117 has a therapeutic potential to prevent secondary cell damage following traumatic brain injury.
Recent studies have identified the distinct existence of flat-type colorectal tumors. The low incidence of ras gene mutations in these tumors suggests that their genetic pathways of tumor progression may be different from those of the polypoid type. To elucidate further genetic alterations in flat-type colorectal tumors, codon 201Arg/Gly polymorphism in the DCC (deleted in colorectal carcinoma) gene was analyzed in normal tissue (normal colonic mucosa or peripheral lymphocytes) and in tumor tissue from 191 patients with colorectal tumors (36 patients with flat-type colorectal tumors, 81 patients with polypoid-type colorectal tumors, and 74 patients with advanced carcinomas). For normal controls, 30 samples obtained from patients who had neither colorectal tumors (confirmed by total colonoscopy) nor a family history of colorectal carcinoma were analyzed. DCC gene codon 201Arg/Gly polymorphism was investigated by polymerase chain reaction-based restriction fragment length polymorphism analysis, fluorescence-based dideoxy sequencing, or both. For the flat type, the frequency of codon 201Gly of the DCC gene was 64% and 54% in the normal tissue of patients with adenoma with high-grade dysplasia and submucosal carcinoma, respectively. It was 49%, 52%, and 49% in the normal tissue of patients with polypoid-type adenoma with high-grade dysplasia, submucosal carcinoma, and advanced carcinoma, respectively. In the normal tissue, codon 201Gly of the DCC gene was more frequently observed in patients with flat-type adenoma with low-grade dysplasia (67%) than in those with polypoid-type adenoma with low-grade dysplasia (18%) or in normal controls (17%, P < 0.05, chi2 test). Codon 201Arg/Gly polymorphism in tumor tissues did not differ from that in the corresponding normal tissues, except for 10 cases of carcinoma with loss of heterozygosity (LOH). In carcinomas with LOH, preferential loss of the codon 201Arg allele was noted (9/10 cases). These results suggest that codon 201Gly of the DCC gene is not only associated with flat-type colorectal tumors, but that it may serve as a useful genetic marker for identifying groups at higher risk for colorectal cancer.
A rare case of mizoribine-induced acute pancreatitis is presented. A 39-year-old female with RA was admitted to our hospital because of upper abdominal pain, fever and the elevation of serum amylase concentration. Acute pancreatitis was diagnosed. Mizoribine (MZB) had been administered for 12 days for the treatment of RA before the onset of pancreatitis. Withdrawal of MZB soon resulted in the improvement of the disease. She was asymptomatic for the next few weeks. The pancreatitis recurred 36 hours after she took MZB again on her own judgement for arthralgia. This clinical course strongly suggested that her pancreatitis was due to MZB. Acute pancreatitis due to MZB has never, to our knowledge, been reported. MZB is commonly used for the treatment of RA. Therefore the clinician should take care for the complication of acute pancreatitis even though it is rare.
Advanced esophageal carcinoma invades adjacent structures, and its resection without residual tumor is difficult. Preoperative chemotherapy and combined modality therapy are being tried to improve survival in patients with T4 esophageal carcinoma. For these cases, chemotherapy with 5-fluorouracil and cisplatin (FP) is known to be not so effective. For 17 patients with T4 esophageal carcinoma in 2 institutes, treated primarily with chemotherapy with 5-fluorouracil, cisplatin and adriamycin (FAP), the response rate was 76%. Operation was performed in all of them after 2-3 courses of FAP, and curative resection without resection of adjacent structure was carried out in 14 cases (82%). Treatment with FP concurrent with more than 50Gy of radiation (CRT) was effective for patients with T4 esophageal carcinoma, its response rate was 72.80% in Japanese literature, and resectability rate was 37-48% after treatment. All of our 3 cases had partial response, but resection was not performed because patients refused surgery. Phase II trial of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy was carried out for 45 patients with clinical stage T1-4N0-1M0 in an attempt to improve the result of concurrent chemoradiation in America (RTOG), and the overall median survival was 20 months. But this treatment will not be used, because treatment-related death was seen in 10%. We think that FAP and CRT are the most effective neoadjuvant therapy in patients with T4 esophageal carcinoma. If curative resection is possible after treatment, operation should be done to improve prognosis.
In a randomized, double-blind, placebo-controlled study beginning 4 weeks after uncomplicated acute myocardial infarction, it was established that the baseline plasma tissue factor antigen level was significantly higher in patients with myocardial infarction than in control subjects, and enalapril therapy significantly reduced the elevated plasma tissue factor antigen level. This may be associated with the reduction in the risk of coronary thrombosis seen with the use of angiotensin-converting enzyme inhibitors.
We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.
Explore the source record for details and available documents.
The peak incidence of esophageal cancer is in the sixth decade, but the number of resections in patients older than 70 is increasing. 184 patients who underwent esophageal resections (C > or = 1) were divided into five groups according to age; Group A: under 50, B: 50s, C: 60s, D: 70s E: over 80. Five-year survival for Group D (20.5%) was much lower than other groups. Group E had better 1- and 2-year survival than Group D. Preoperative condition, stage and postoperative course were investigated in 145 patients who underwent subtotal esophagectomy with two-field lymphadenectomy and reconstruction with the stomach. In Group D, more respiratory dysfunction and abnormality of electrocardiogram were seen than Group C (p < 0.05) preoperatively. There was no difference in stage. Group D had higher incidence of postoperative pneumonia, abnormal ECG (p < 0.01) and delirium (p < 0.05). Group D had less cancer deaths and more deaths from other diseases. These results indicate that patients older than 70 should be called aged and it is safe to reduce the lymph node dissection in the upper mediastinum for these patients.
The DCC gene is one of several genes altered during tumorigenesis. Recent studies demonstrate the existence of 29 exons and it spans 1.4 Mb. DCC gene is a candidate tumor-suppressor gene encoding a protein with a sequence similarity to cell adhesion molecule. Although the mutation of DCC gene was few, high incidence of LOH and decreased mRNA expression in colorectal cancer especially with hepatic metastasis was observed. These DCC gene abnormalities possibly be related to predictive marker for liver metastasis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To investigate the biological function of p53 in colon carcinoma cells, a wild-type p53 expression plasmid under the control of the human cytomegalovirus promoter was stably transfected into the human colon adenocarcinoma cell line WiDr, which carries a mutation of the p53 gene at codon 273. Exogenous wild-type p53 transcripts were detected at various expression levels in 8 of 117 G418-resistant clones. The growth rates of the wild-type p53+ clones in culture did not change significantly. The efficiency of colony formation in soft agar, however, was completely suppressed in two wild-type p53+ clones. This is the first to demonstrate the feasibility of stable transfection of the wild-type p53 gene under the control of non-inducible promoter in human colon cancer cells. The major alteration found was that wild-type p53+ cells which were incubated with anti-Fas IgM showed marked cytolysis with preferential over-expression of wild-type p53 accompanied by overexpression of a cyclin-dependent kinase inhibitor, WAF1, whereas the endogenous mutant p53 retained its expression level. The findings suggest that a Fas-initiated pathway is incidentally linked to a p53-dependent apoptotic pathway through the reconstituted wild-type p53 gene in WiDr cells. This model should help elucidating the additional role of the p53 tumor suppressor gene and the mechanism of apoptosis in colon carcinoma cells.
Explore the source record for details and available documents.
HLA-DRB1 allele typing was performed by the PCR-RFLP method on 59 ulcerative colitis (UC) patients and 136 healthy controls. Phenotypic frequencies of HLA-B52 and DR2 were significantly increased among the UC patients, serologically. DNA typing of HLA-DRB1 revealed that the genotypic frequency of DRB1*1502 was higher in UC than in the controls (49.2% vs 17.6%; P < 0.0001). In the analysis of clinical parameters, 82.8% of patients bearing DRB1*1502 were treated with corticosteroids. DRB1*1501 and DRB1*1502 differ in only one amino acid at residue 86 (valine vs glycine), and 66% of the UC patients carried two glycines at position 86 in the HLA-DR beta-chain (vs 51% of control; P < 0.05). These observations suggest that the presence of Gly-86 in the HLA beta-chain and surrounding amino acid sequence of HLA-DRB1*1502 is strongly associated with susceptibility to UC.
Ninety-three patients with gastric ulcers larger than 10 mm in diameter were randomly divided into two groups. Seventy patients received lansoprazole 30 mg once daily and 23 patients received cimetidine 400 mg twice daily. Ulcer healing was assessed by measuring changes in the longitudinal diameter of the ulcer at 2, 4, and 8 weeks after the start of treatment. In the lansoprazole group, ulcer diameters became significantly smaller than those in the cimetidine group. In the lansoprazole group, ulcer diameters did not differ significantly between patients younger than 65 years of age and those 65 or older at the evaluation points. However, in the cimetidine group, ulcer diameters became much smaller in patients younger than 65 years of age than in older patients. These results suggest that the potent acid suppression afforded by lansoprazole led to effective healing of gastric ulcers even in elderly gastric ulcer patients with defective mucosal protection.