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Biomedical subjects

M Hiraishi

Publications and source records attributed to M Hiraishi.

At least 19 recordsLinked to original sources

Isolation and characterisation of cycloheximide-sensitive mutants of Aspergillus nidulans.

Aspergillus nidulans is a non-pathogenic fungus with well-developed genetics which provides an excellent model system for studying different aspects of drug resistance in filamentous fungi. As a preliminary step to characterizing genes that confer pleiotropic drug resistance in Aspergillus, we isolated cycloheximide-sensitive mutants of A. nidulans, which is normally resistant to this drug. The rationale for this approach is to identify genes whose products are important for drug resistance by analysing mutations that alter the resistance/sensitivity status of the cell. Fifteen cycloheximide-sensitive (named scy for sensitive to cycloheximide) mutants of A. nidulans were isolated and genetically characterised. Each scy mutant was crossed with the wild-type strain and five of the crosses gave 50% cycloheximide-sensitive progeny suggesting that they carry a single mutation required for cycloheximide sensitivity. We examined ten scy mutants for resistance/sensitivity to other drugs or stress agents with different and/or the same mechanism of action. Six of these mutants exhibited other altered resistance/sensitivity phenotypes which were linked to the cycloheximide sensitivity. These six mutants were analyzed by pairwise crosses and found to represent six linkage groups, named scyA-F. One of the mutants showed fragmentation of its vacuolar system and, in addition, its growth was osmotic, low-pH, and oxidative-stress sensitive.

Aspergillus nidulans↗

A combination of laser therapy, radiation therapy, and stent placement for the palliation of complete malignant bronchial obstruction.

We treated a complete obstruction of the left mainstem bronchus due to nonresectable recurrent esophageal carcinoma with a combination of laser therapy, radiation therapy, and the placement of an expandable metallic stent. The patient survived 1 year after the first therapy, with good quality of life. We conclude that a combination of laser ablation, radiotherapy, and stent placement can improve survival and quality of life for the patients with complete malignant bronchial obstruction.

Aged↗

Impairment of autonomic function induced by posture change in postmenopausal women.

This study was designed to determine if there is a difference in autonomic regulation induced by posture change between postmenopausal and young women. To evaluate autonomic nervous system function, spectral analysis of heart rate variability (HRV) was done in postmenopausal women (n = 13, 46-59 years of age), age-matched men (n = 8, 45-55 years of age), and young women (n = 10, 20-37 years of age) for 3-min periods of controlled frequency breathing (15 breaths/min) in supine followed by sitting positions. In the supine position, the R-R interval variation in older persons decreased significantly compared with that during the follicular phase in young women. Furthermore, the high-frequency (HF) components of HRV, which reflect only parasympathetic activity, were lower in older subjects than in young women. Following a change of position from supine to sitting, the HF component did not change significantly in the postmenopausal women or the men, but the low/high frequency (LF/HF) component ratio, which reflects the balance of autonomic nerve activities, increased significantly in the men. These results suggest that cardiac parasympathetic tone may be reduced in older persons in comparison with young women. Furthermore, arterial baroreflex control of parasympathetic nerve activity caused by posture changes is impaired in the postmenopausal women and aged-matched men. The baroreflex control of the sympathetic component is maintained in the men but not in the postmenopausal women. These differences might result in part from changes in the level of female hormones.

Adult↗

Mastoid pneumatization in children with congenital cholesteatoma: an aspect of the formation of open-type and closed-type cholesteatoma.

OBJECTIVES: To clarify mastoid pneumatization in children with congenital cholesteatoma and compare their clinical characteristics. STUDY DESIGN: The mastoid pneumatization of 34 children with congenital middle ear cholesteatoma, of 34 age-matched children with unilateral acquired cholesteatoma, and of 17 age-matched control children without middle ear diseases was studied. METHODS: The sizes of the mastoid cells were measured from 1.5-mm sliced semiaxial sections of a temporal bone computed tomography scan. The sum of the two areas from the two images, one showing the lateral semicircular canal and the other, 3 mm below this, was defined as the area of the pneumatized mastoid cells. RESULTS: The mastoid cells in ears of children with congenital cholesteatoma were poorly pneumatized compared with those of control children without middle ear diseases, but were better pneumatized compared with those of children with acquired cholesteatoma. In children with congenital cholesteatoma, the degree of pneumatization in the cholesteatoma side was significantly poorer than that in the opposite side. A well-pneumatized mastoid was seen in ears with no episode of otitis media, in ears with the open-type cholesteatoma, and in ears with ossicular anomalies. CONCLUSIONS: The presence of cholesteatoma matrix accelerates the inflammatory response when middle ear infections occur, and this probably leads to the suppression of mastoid pneumatization. The authors also propose the hypothesis that cholesteatoma in most congenital cases is the open type, and that middle ear inflammation may contribute to the formation of cystic and closed-type cholesteatoma.

Adolescent↗

[Adjuvant chemotherapy with UFT or UFT with OK-432 to patients with gastric and colorectal cancer. Kanto Adjuvant Study Group].

In Japan, long-term oral therapy with tegafur in combination with immunopotentiators is commonly used as adjuvant therapy after curative resection of gastric or colorectal can for gastric and colorectal cancer. When the outcome was analyzed in terms of the relative performance (R.P.) and the individual dose intensity (I.D.I.) of OK-432, gastric cancer patients with a R.P. of 0.5 or higher tended to have a better survival curve. There were no marked differences in lymphocytes subsets, except that the Leu 7 level at 3 months after gastric cancer resection was significantly higher (p < 0.05) in group B than in group A. Thus, no inhibition of the anticancer effect of UFT was noted during long term combination therapy with UFT and an immunopotentiator as postoperative adjuvant therapy for patients who underwent curative resection of gastric or colorectal cancer. The results suggest that UFT combined with long-term OK-432 maintenance therapy may contribute to improve survival rates in gastric cancer patients.

Adjuvants, Immunologic↗

Three histologically different tiny gastric cancers developing adjacent to each other, resected endoscopically in a single mucosal piece.

In this report, we describe a case with triple tiny cancers of the stomach developing adjacent to each other and resected endoscopically in a single mucosal piece. The three cancers differed from each other histologically. The surrounding mucosa was atrophic pyloric gland mucosa with moderate to severe intestinal metaplasia. Both histological and serological examinations were negative for Helicobacter pylori. Each of the three cancer lesions was positive for mutant p53 product immunohistochemically. None of the cancers were positive for Epstein-Barr virus sequence in an in situ hybridization analysis. These lesions suggest that certain local conditions in the gastric mucosa can result in carcinogenesis of different histological types of gastric cancers.

Adenocarcinoma↗

Segmental occlusion of the pancreatic duct with prolamine to prevent fistula formation after distal pancreatectomy.

OBJECTIVE: The authors used prolamine (Ethibloc, Ethicon GmBH, Norderstedt, Germany) for segmental obstruction of the pancreatic duct to prevent pancreatic fistula development after distal pancreatectomy combined with total gastrectomy for gastric malignancies. SUMMARY BACKGROUND DATA: Although the initial clinical application of prolamine was pancreatic duct obstruction for patients with pancreatitis and undergoing pancreatic transplantation and pancreaticoduodenectomy for pancreatic cancer, there are no reports on prevention of pancreatic fistula formation after distal pancreatectomy. METHODS: Prolamine (0.2 mL) was injected into the distal segment of the main duct in the remaining pancreata of 51 patients. Small pancreatic ducts on the cut surface, from which prolamine extravasates, were closed by ligation, the main duct was ligated doubly, and the transected pancreatic margin was closed 15 minutes after phenylpropanolamine hydrochloride injection. RESULTS: No patient developed a pancreatic fistula or the complication of arterial bleeding due to prolonged infection. CONCLUSION: Segmental obstruction of the pancreatic duct with prolamine is useful for preventing pancreatic fistula development after distal pancreatectomy.

Amylases↗

[Clinical evaluation of sequential MTX/5-FU therapy for gastric cancer].

Sequential MTX/5-FU therapy was performed on 64 patients with unresectable or recurrent gastric cancer. The therapy was most effective in patients with poorly differentiated type gastric cancer. We adopted the intermediate (MTX: 100mg/m2, 5-FU: 800mg/m2) and low (MTX: 30mg/m2, 5-FU: 600 mg/m2) dose regimens. The latter was performed at the outpatient clinic every 2 weeks. This therapy was used for patients with Borrmann type 4 gastric cancer or advanced gastric cancer of poorly differentiated type as postoperative adjuvant chemotherapy. The response rate was 25% in 44 evaluable patients, and 33% in patients with poorly differentiated type cancer. As an adverse effect, leukopenia (grade 3, 4) was observed in 4 patients (9%). The 5-year cumulative survival rate of the sequential MTX/5-FU therapy group (52.6%) was much better than the conventional adjuvant chemotherapy group (32.1%) in patients who underwent curative resection with Borrmann type 4 gastric cancer. One patient survived more than 900 days after non-curative resection with peritoneal dissemination (P 3) after low dose therapy of sequential MTX/5-FU. For the patients who did not respond to the MTX/5-FU therapy, MTX/CDDP/LV/5-FU therapy was adopted. This protocol consisted of MTX (30 mg/m2 iv; day 1), CDDP (60 mg/m2 div; day 2 and day 9), Leucovorin (30 mg iv; day 2-9) and 5-FU (250 mg/m2 div; day 2-9). We also performed MTX/CDDP/LV/5-FU therapy for the treatment of differentiated type gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Influence of the mucin coat on the survival of rabbit and mouse embryos stored at 0 degrees C.

To examine the factors affecting the survival of refrigerated embryos, rabbit and mouse morulae were stored at 0 degrees C in modified phosphate-buffered saline (PB1) or in PB1 containing 0.75 M sucrose. Survival was defined as the ability to develop into an expanded blastocyst in culture. The data was analyzed with special reference to the presence of a mucin coat around the embryos. When rabbit morulae were stored in isotonic PB1 for 2, 4, 6, and 8 days, survival rates were 98%, 88%, 85%, and 50%, respectively. However, if the mucin coat had been removed before storage, the rates were lower (95%, 75%, 36%, and 3%, respectively). Sucrose impaired the survival of rabbit morulae irrespective of the presence of the mucin coat. Only 11% of mouse morulae survived 2 days of storage in PB1 medium, but if the medium contained sucrose, survival rates after storage for 2, 3, 4, and 5 days were higher (83%, 55%, 31%, and 7%, respectively). To provide them with a mucin coat around the zona pellucida, mouse embryos were incubated in a rabbit oviduct. Survival rates of these embryos after storage in the presence of sucrose did not decrease over 4 days of refrigeration (98-92%), and the rates after storage for 5, 6, and 7 days were 65%, 40%, and 30%, respectively; embryos that had been stored for 5 days were transferred to recipient mice, and live young were born. Agar embedding of mouse morulae did not have the same effect as the mucin coat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Activities of thymidylate synthetase and thymidine kinase in gastric cancer.

In a previous clinical study, sequential methotrexate and 5-fluorouracil has shown improved efficacy for treating advanced gastric cancer of the poorly differentiated type. In this study, we investigated whether difference in the levels of thymidylate synthetase (TS) and thymidine kinase (TK) activities in gastric cancer tissue account for selectivity of the treatment. Activity of TS was higher in 19 cases of the poorly differentiated type than in 16 cases of the well differentiated type (P < 0.02), whereas TK activity was lower in the poorly differentiated type than in the well differentiated type (P < 0.01). Thus, the TS/TK ratio was significantly higher in poorly differentiated gastric cancers than in well differentiated cancers (P < 0.001). These results suggest that a greater dependence upon the de novo pathway of pyrimidine synthesis in poorly differentiated gastric carcinomas may enhance the efficacy of sequential methotrexate and 5-fluorouracil treatment.

Adenocarcinoma↗

Multiple strictures of the small intestine after long-term nonsteroidal anti-inflammatory drug therapy.

A 60-yr-old female patient with rheumatoid arthritis presented with nonsteroidal anti-inflammatory drug (NSAID)-induced ileal ulcers which caused intestinal bleeding and multiple strictures. Results of investigations, including radiological, pathological, and bacteriological examinations, were not consistent with Crohn's disease or intestinal tuberculosis. Rather, the lesion was characteristic of "diaphragm disease" caused by NSAIDs. Discontinuance of NSAIDs in combination with administration of ornoprostil (prostaglandin E1-derivative), sucralfate, and sulfasalazine put an end to the intestinal bleeding. This is a rate case of a patient with multiple strictures of the small intestine caused by NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗

[Mechanism of synergism and clinical results of sequential methotrexate and 5-fluorouracil in the treatment of gastric cancer].

Mechanism of synergism and clinical results of methotrexate and 5-fluorouracil (MTX/5-FU) combination therapy for gastric cancer were studied. The response rate against poorly differentiated gastric cancers was 35% in this treatment. This treatment also showed a remarkable effect against cases with pleural and abdominal effusion caused by cancerous disseminations. A promising result was obtained by this treatment as neoadjuvant and postoperative chemotherapy against Borrmann type 4 gastric cancer. A greater dependence on the de novo pathway of pyrimidine synthesis against poorly differentiated gastric carcinoma, which was estimated by the fact that the thymidylate synthetase/thymidine kinase ratio was significantly higher in poorly differentiated gastric cancer than in well differentiated cancer, may potentiate therapeutic results of this treatment.

Adult↗

[Effect of sequential MTX/5-FU therapy for a case of disseminated intravascular coagulation syndrome associated with recurrence of gastric cancer--a case report].

Although a 39-year-old male received the curative operation of total gastrectomy for advanced scirrhous carcinoma of the stomach, recurrence of cancer was occurred soon after the surgery, accompanied by hemorrhagic diathesis from DIC. The abdominal CT scan examination revealed the rapid enlargement in the size of the several lymphnodes around the abdominal aorta, and the blood chemistry tests showed marked increase of the serum CEA value. The sequential chemotherapy with intermediate dose of MTX and 5-FU in conjunction with OK-432 was started to treat the case. This chemotherapy was carried out once a week for 5 times and consequently DIC was led to the perfect remission. Furthermore, CEA level decreased within normal range, and the size of the enlarged lymphnodes at paraaortic area diminished remarkably. Although he complained of nausea and loss of appetite during the treatment, no severe adverse effects such as granulocytopenia, diarrhea, or loss of hair were observed. The successful result in this patient suggests that sequential therapy of intermediate dose of MTX and 5-FU with administration of OK-432 may be effective in the treatment of advanced scirrhous carcinoma of the stomach.

Adenocarcinoma, Scirrhous↗

Effect of oral adsorbent on blood metabolites in hepatic failure dogs.

AST-120 is a specially synthesized carbonaceous adsorbent for oral use. It mainly adsorbs low to middle molecules in the alimentary tract. In the present study, AST-120 was administered to hepatic failure dogs, and blood metabolites were analyzed by high performance liquid chromatography (HPLC). Thirty adult mongrel dogs underwent posta-cavae (P-C) shunts with 40% and 70% hepatectomies. They were divided into two groups, the AST group (n = 19) and control group (n = 11). The AST group received about 0.5 g/kg of the adsorbent intermittently with diet after the operation. The control group was fed the ordinary diet. Body weight, blood ammonia, plasma bile acids were measured, and blood metabolites were analyzed by the multi-column HPLC system. P-C shunt dogs with 70% hepatotectomies died within three months showing about 40-50% body weight loss. HPLC analysis of their plasma showed some specific peaks for middle molecules, about 3000-5000 daltons. After administration of the adsorbent, these peaks were not detected, so it was considered that these substances had been adsorbed.

Administration, Oral↗

Plasma collection using nafamostat mesilate and dipyridamole as an anticoagulant.

Nafamostat mesilate (FUT-175) is a strong protease inhibitor and is used as an anticoagulant in extracorporeal circulation. In the present study, we administered FUT and dipyridamole as anticoagulants during donor plasmapheresis, and the additional effect of dipyridamole was examined. In dogs weighing about 15 Kg, donor plasmapheresis was performed using a cellulose triacetate membrane plasmaseparator (PEX-15, Nipro), and 300 ml of filtrated plasma was obtained within 30 minutes. These dogs were divided into two groups, 50 mg/h of FUT alone was infused (group A, n = 10), and the same dose of FUT and 25 mg/h of dipyridamole were infused (group B, n = 5) during plasmapheresis. Changes of the coagulation system, blood cell counts and complement system were investigated. In clinical cases, an artificial liver support therapy using FUT as an anticoagulant was performed on 8 patients with acute liver failure, and blood compatibility was examined. In dogs, RBC counts and hematocrits were almost stable, but WBC counts were decreased to about 70% of the previous value. Platelets counts were about 60% and 80% of the previous value, in group A and group B, respectively, at the end of the plasmapheresis (P less than 0.01). Clotting factor VII was diminished to about 20% and 35% of the previous value in group A and B, respectively. In clinical cases, all patients received the plasma exchange combined with hemodialysis using FUT as an anticoagulant, and no distinct side effect was observed during plasma exchange.

Adult↗

The effect of oral adsorbent on surgically induced hepatic failure.

The oral adsorbent AST-120 is one type of activated carbon for oral use. In the present study, AST-120 was administered, to clarify its effect, on surgically induced hepatic failure in dogs and rats. Portacaval shunts and varying extents of hepatectomies were performed on 44 dogs. Eleven dogs were given an ordinary diet (control group), and 33 dogs received the oral adsorbent with an ordinary diet after the operation (AST group). Plasma bile acids and ammonia increased, and body weight decreased in both groups. However, after the administration of AST-120, the plasma bile acids and ammonia decreased significantly, and the body weight tended to increase in the AST group. Portacaval shunts and about 70 per cent hepatectomy were performed on 59 Sprague-Dawley rats. These rats were divided into two groups, diet with the oral adsorbent (AST group, n = 19) and an ordinary diet alone (control group, n = 40). DNA synthesis and protein synthesis of the liver were measured on the 5th, 10th and 20th postoperative days using radioisotopes in these rats. Both DNA and protein synthesis of the liver were increased significantly in the AST group. Histological examination revealed many more glycogen granules in the cytoplasm of hepatocytes in the AST group compared to the control group on the 5th postoperative day. It was suggested that some metabolic toxin was adsorbed by AST-120 in the alimentary tract.

Adsorption↗