Biomedical subjects
Publications and source records attributed to T Imada.
Peptidyl difluoromethylene ketone derivatives were designed to take advantage of probable additional interactions with the S' subsite of human heart chymase. They showed potent inhibitory activities against human heart chymase and were more efficient than bovine chymotrypsin.
Appropriate structural modification of the difluoromethylene ketone derivatives at both P3 and P' positions led us to the discovery of peptidyl human heart chymase inhibitor 12h which shows potent activity with Ki = 6 nM and high selectivity against closely related serine protease bovine alpha-chymotrypsin (chymotrypsin Ki = > 100 microM). Using the compound 12b, a docking study with human heart chymase was carried out to presume probable interactions.
Explore the source record for details and available documents.
It is well known that squamous cell carcinoma of the esophagus can be associated with carcinoma of other organs. We report herein the rare case of a 60-year-old man who developed synchronous bilateral lung cancers after undergoing esophagectomy for esophageal cancer. Staged bilateral lobectomy was successfully performed to minimize respiratory complications 3 years after his esophagectomy. This case report serves to demonstrate that aggressive and careful surgical approach with adequate followup offers the chance of long-term survival for patients with multiple primary cancers.
Endobronchial hamartomas are only rarely encountered. They cause irreversible lung damage due to bronchial obstruction if not diagnosed early and treated properly. Among the various treatments for this rare disease, a surgical resection remains the most popular. We herein report a case of a 53-year-old man presenting with an endobronchial hamartoma which was successfully excised by laser irradiation via a rigid bronchoscope, along with a review of 113 patients with this disease reported in the literature.
After considerable experience with laparoscopic cholecystectomy (LC) using four ports, we began using three-port LC in October 1993 and have performed 130 LCs with this procedure up to May 1996. The procedure was successful in 119 patients. In 6 patients fourth port was used, and in another 5, the procedure was converted to open laparo-tomy. Cooperative manipulation of the surgical instruments between the operator and assistant is very important for this procedure, for exposing Calot's triangle and dissecting the gallbladder from the gallbladder bed. The use of an ultrasonic aspiration system (Sumisonic ME 2400; Sumitomo Bakelite, Tokyo, Japan) made it easier to identify the cystic duct and artery, especially in patients with chronic inflammation or dense adhesions. We encountered no problems with cannulation into the cystic duct for intraoperative cholangiography, and there were no intra- and postoperative complications in this series. We achieved good results, similar to those achieved with the four-port technique. This technique is technically feasible and safe, and it has esthetic and cost advantages compared with the four-port technique. However, the operator who performs three-port LC should not hesitate to add another port, or to convert to open laparotomy, whenever any difficulties occur during this procedure, to prevent critical complications.
It is well known that surgical intervention on the stomach will greatly alter gastric function and gastric emptying. In this study, we evaluated the difference in postoperative gastric remnant emptying following pylorus-preserving gastrectomy (PPG) and conventional subtotal gastrectomy (CDG) using sulfamethizole capsule food. The subjects comprised 18 patients who underwent PPG and 23 who underwent CDG for early gastric carcinoma. While delayed gastric emptying was observed early after PPG, 1 year after PPG it was markedly accelerated compared with that measured in the early postoperative period. However, it was slower than that in the CDG patients. On the other hand, rapid gastric emptying was observed early after CDG and did not change with time. These findings stress that although PPG results in stasis in the early postoperative period, it seems to prevent unduly rapid emptying.
OBJECTIVE: Frequency organization in the human somatosensory cortex was studied. DESIGN AND METHODS: Somatosensory evoked magnetic fields (SEFs) from 12 subjects were measured following vibratory stimulation of the index finger by using a 122 channel whole head SQUID system. Sensory stimuli comprising a 40 ms vibration at frequencies of 50, 100, 200 and 400 Hz were delivered to the volar surface of the tip of the right index finger. Using a single dipole model, the sources of the magnetic fields were estimated and mapped onto magnetic resonance images of each subject. The analysis of variance test (ANOVA) was used for statistics. RESULTS: Source localization was determined on the main two peaks (M60 and M110) of the SEFs. All of the sources were located in the area 3b of somatosensory cortex (SI). There were no statistically significant differences between the locations of the dipoles evoked by different frequency stimulations. CONCLUSIONS: These results demonstrate the absence of systematic frequency organization at the hand representation area of the SI cortex. We speculate that high frequency vibration above 100 Hz are coded by the fast-spiking interneurons which synapse with Pacinian pyramidal neurons in SI.
A 71-year-old woman presented with an abdominal mass and ascites and was subsequently admitted to our hospital in June 1995. Further examination revealed that the mass was malignant and, as a result, surgery was indicated. However, the mass demonstrated widespread peritoneal dissemination, which therefore could not be resected, and pathological findings suggested a malignant peritoneal mesothelioma. The patient showed a remarkable response to combined chemotherapy with an accompanying intraperitoneal injection of cisplatin and etoposide and an intravenous injection of caffeine. However, owing to side effects, this regimen was discontinued. The patient was administered a combination drug of uracil and tegafur (UFT) in addition to intraperitoneal injection of cisplatin as an outpatient. By the 223rd day after surgery, the tumor mass and ascites had completely disappeared according to the CT. Hence chemotherapy was judged to have resulted in complete remission. Such a marked response to chemotherapy is rare in an advanced malignant peritoneal mesothelioma such as the present case. Eight months later, the tumor recurred in the pleura. Another regimen of chemotherapy with cisplatin and CPT-11 was performed. However, this treatment proved ineffective. The patient subsequently died of respiratory failure in January 1997 due to the mesothelioma. This is a case report of complete remission of malignant peritoneal mesothelioma by combined chemotherapy.
1. The present study was designed to investigate the anti-atherosclerotic effect of AE0047, a calcium channel blocker, and to compare it with that of nilvadipine in cholesterol-fed rabbits. Furthermore, the effects of AE0047 on low-density lipoprotein (LDL) oxidation were studied in vitro. 2. A 7 week treatment period with AE0047 (3 and 10 mg/kg, p.o.) led to a dose-dependent reduction in the lipid deposition area by Oil Red-O staining (surface index) without affecting serum lipid levels. There was no reduction in the surface index following treatment with the same dose of nilvadipine (10 mg/kg). 3. In a vehicle-administered high-fat diet group of rabbits, levels of total cholesterol (TC) and esterified cholesterol (EC) and calcium content in the aorta were increased approximately two- to three-fold over those of the normal diet group. Increased levels of TC and EC and calcium content were reduced to the same levels as the normal diet group by AE0047 treatment, whereas nilvadipine did not affect TC and EC levels. 4. In an in vitro study, AE0047 (10 micromol/L) inhibited LDL oxidation and the aggregation of apolipoprotein (Apo) B-100 induced by Cu2+. Furthermore, AE0047 inhibited the degradation of oxidized LDL by macrophages. In contrast, the same dose of nilvadipine (10 micromol/L) did not inhibit either LDL oxidation or the aggregation of ApoB-100. 5. In summary, AE0047 inhibited LDL oxidation, resulting in a decrease of its uptake into macrophages and an inhibition of cholesterol esterification. This leads to an anti-atherosclerotic effect of AE0047. Thus, AE0047 may have therapeutic potential in preventing cardiovascular disease in hypertensive patients.
Bovine follicle fluid and oocytes surrounded by follicular epithelial (FE) cells were collected from ovaries of two heifers persistently infected with bovine viral diarrhea virus (BVDV). BVDV was present in the follicle fluid at a higher titer than in serum. The oocytes were matured in vitro under culture conditions of 39 degrees C in humidified air containing 5% CO2. In vitro fertilization was performed after 24 hr in culture (the day of insemination was defined as day 1), and culture was continued through day 10. BVDV was present in the culture medium at titers of 10(2.25) to 10(3.25) TC(I)D50/0.1 ml. The virus was also detected in FE cells collected on day 10. Viral antigen was demonstrated in the cytoplasm of FE cells by the indirect immunofluorescence technique. However, no BVDV was detected in the embryos on day 10. These findings suggested that the oocytes or embryos were unlikely to be infected with BVDV, but that the FE cells were infected with BVDV and supported virus replication in cattle persistently infected with BVDV.
BACKGROUND: Malnutrition, gallbladder dysfunction, dumping syndrome, reflux esophagitis, and gastritis of the remnant stomach are unfavorable sequelae in patients undergoing gastrectomy. Operative procedures should be improved to ensure such patients a satisfactory quality of life. METHODS: After operation, gallbladder function, reflux gastritis, gastric emptying, and caloric intake were evaluated in 20 patients with early gastric cancer undergoing pylorus-preserving gastrectomy (PPG) and 25 patients undergoing conventional distal gastrectomy (CDG). RESULTS: The resting gallbladder area increased significantly after CDG. In contrast, after PPG the gallbladder area showed no significant change and the contraction rate decreased slightly. After CDG, emptying was much more rapid for the first 30 minutes after ingestion of a meal. Although delayed emptying was observed early after PPG, the rate of emptying increased with time. Gastric pH was lower and gastric mucosal injury was milder in patients undergoing PPG. These results are attributed to preserved pyloric function. The caloric intake and changes in body weight after operation were similar in both the CDG and PPG groups. CONCLUSIONS: PPG has advantages over CDG in terms of gallbladder function, the condition of the remnant stomach, and gastric emptying, PPG should be used in carefully selected patients with early gastric cancer to improve their quality of life.
Auditory evoked cortical responses, electric. N1 and magnetic N1m, increase when the interstimulus interval (ISI) increases. We assumed that the response to a tone is mainly affected by the immediately preceding ISI, by the immediately preceding pause between stimuli (PBS) and by the previous stimulus duration (PSD). These 3 values are connected by the following expression: ISI = PBS + PSD. We examined the dependence of the auditory evoked brain magnetic responses on the ISI with the constant PSD (conventional paradigm), on the PBS with the constant ISI, and on the ISI with the constant PBS. Peak latencies and peak amplitudes of the 3 components, P1m, N1m and P2m, are recorded in one block using all possible combinations of 5 PSDs (0.05, 0.5, 1.0, 1.5 and 2.0 s) and 5 ISIs (0.5, 1.0, 1.5, 2.0 and 2.5 s). Peak latencies of these 3 components do not show any significant dependence either on the PBS or on the ISI. Neither the PBS nor the ISI brings a statistically significant effect on the P1m peak amplitude. On the other hand, the N1m peak amplitude increases as either the PBS (constant ISI) or the ISI (constant PSD) increases. The regression coefficient to the PBS is more than a double of that to the ISI. Moreover, the ISI does not show any significant effect on the N1m peak amplitude when the PBS is constant. This stronger PBS effect means that the N1m peak amplitude dependence on the ISI, which has been reported in several papers using the constant PSDs, includes more dependence on the PBS. The P2m peak amplitude shows the same tendency as the N1m because of the strong correlation in peak amplitude between them.
Bovine oocytes enclosed by follicular epithelial (FE) cells were exposed to bovine herpes virus-1 (BHV-1), bluetongue virus (BTV) and akabane virus (AV), matured in culture for 24 h and then in vitro fertilized. In the BHV-1-exposed group, BHV-1 was isolated from medium 3 days after in vitro fertilization at a high titer, and a severe cytopathic effect was observed in the FE cells. Oocytes in the BHV-1-exposed group developed to the 2-cell to 8-cell stage, but failed to develop into blastocysts. In the BTV-exposed group, BTV replication was observed in the FE cells during in vitro embryo development into blastocysts. In the AV-exposed group, no distinct AV replication was detected in FE cells during in vitro embryo development. These results indicate that these viruses failed to infect zona-intact oocytes or embryos during in vitro maturation and culture.
Flow cytometric analysis of nuclear DNA ploidy was performed to evaluate the clinical significance of DNA-ploidy heterogeneity and DNA-index heterogeneity between the superficial layer and the deep layer of the tumor obtained from 88 advanced gastric cancer patients. DNA-ploidy heterogeneity was observed in 28 patients (31.8%) and characterized mainly by diploidy in the superficial layer and aneuploidy in the deep layer. More than 10% difference in the DNA index among aneuploidy (DNA-index heterogeneity) was observed in 10 (26.3%) of 38 patients with aneuploidy. There was no tendency for the DNA index to increase with deep infiltration. DNA-ploidy and DNA-index heterogeneities were not correlated with the various clinicopathological characteristics. Patients with aneuploidy had significantly poorer prognosis than did those with diploidy. The survival rate for patients with DNA heterogeneity was not significantly different from that for patients without DNA heterogeneity. These results suggest that the DNA-ploidy pattern may be an important prognostic factor, but that DNA heterogeneity may not have an impact on the survival in advanced gastric cancer.
The combination effect of 5-fluorouracil (5-FU) and cisplatin was examined in terms of the proliferation, morphology and expression of Ki-67 antigen, and propidium iodide (PI) staining using four cultured human gastric cancer cell lines, and we assessed how such activity was affected by the exposure time and the timing of treatment. MKN-1, MKN-28, MKN-45 and MKN-74 cells were exposed to various concentrations of 5-FU for 72 h and cisplatin for 8 or 72 h. At IC50, MKN-28 cells were more sensitive to 5-FU than other cell lines, whereas MKN-1 and MKN-45 cells were more sensitive to cisplatin than other cell lines. The cell growth-inhibitory activity of cisplatin was found to be 'area under the curve' dependent. When 5-FU and cisplatin were combined simultaneously, the combination effect was higher than that of 5-FU or cisplatin alone. On the other hand, when cisplatin was applied before 5-FU, there was no potentiation of the cell growth-inhibitory activity by combination treatment. In 5-FU-treated MKN-74 cells, the size, morphology and PI staining of nuclei were almost the same as those of the untreated cells, and the expression of Ki-67 antigen was less than that of the untreated cells. In cisplatin-treated MKN-74 cells, the size of cells and nuclei was larger than that of the untreated cells and fragmentation of nuclei was observed. The expression of Ki-67 antigen was less than the untreated cells but more than that of 5-FU-treated cells. In the cells treated with 5-FU and cisplatin in combination, the above changes were an intermediate of those of 5-FU-treated cells and cisplatin-treated cells. In conclusion, the cell growth-inhibitory activity of 5-FU and cisplatin against gastric cancer cells was potentiated by the combined treatment with 5-FU and cisplatin simultaneously, but not with cisplatin followed by 5-FU.
We encountered a rare case of postbulbar ulcer caused by adjuvant chemotherapy after gastrectomy. A 64 year-old woman, who received chemotherapy with CDDP-5-FU after gastrectomy, developed severe hematemesis. Endoscopic examination revealed a gigantic ulcer at the anal site of Vater's papilla. The ulcer was healed with PPI and soft diet.
A conventional equivalent current dipole estimation provides one of the quantitative measures to evaluate the discrepancy between two single-dipole-like magnetic field patterns, though there is one problem; all stimulus positions in the visual field do not necessarily contribute to the generation of a single-dipole-like magnetic field. Another important problem occurs when the field pattern is complex and cannot be approximated by a dipole. This makes it difficult to evaluate the discrepancy between two magnetic field patterns by the dipole parameters. In this paper, we determined the stimulus positions adequate for generating single-dipole-like magnetic field patterns by evaluating the magnetic field's goodness-of-fit to the field generated by a single dipole. We propose to use a similarity (SIM) as a quantitative measure of the discrepancy between two complex magnetic field patterns. The SIM is defined as an angle between two magnetic field vectors. We evaluated the discrepancy between the 100 ms post-stimulus responses to pattern-reversal (Rv) stimulus, pattern-onset (Pat) stimulus, and luminance-onset (Lumi) stimulus. The following results were obtained: (1) Stimulation of some of the octants in the fovea, far from the vertical meridian, elicited a single-dipole-like magnetic field pattern at a latency of 100 ms, though stimulation of the central part of the fovea, and stimulation of the octants along the vertical meridian, did not elicit a single-dipole-like magnetic field pattern; (2) The discrepancy between responses was quantitatively evaluated by the SIM even if the field patterns were complex; (3) The SIM analysis showed that the discrepancy between the responses to the Rv and the Lumi stimuli, as well as that between the responses to the Pat and the Lumi stimuli, were greater than that between the responses to the Rv and the Pat stimuli.