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Biomedical subjects

M Sunagawa

Publications and source records attributed to M Sunagawa.

At least 109 records · Page 6Linked to original sources

Thoracic esophageal diverticula. Why is operation necessary?

Diverticula of the thoracic esophagus are uncommon disorders. The indications for surgical intervention in asymptomatic or minimally symptomatic patients are unclear. Among 20 patients referred during a 20-year period, 6 were male and 14 female, with a median age of 65 years. Two had had previous diverticulectomies. Dysphagia was present in 9 (45%) and regurgitation in 11 (55%). Nine patients had severe nocturnal cough with symptoms of aspiration. In two of these nine and in three other patients (25%), pulmonary symptoms were the only manifestation of disease, with no or minimal esophageal symptoms. In one patient the diagnosis of the presence of bronchial asthma for several years was incorrect; one patient had massive aspiration before hernia repair, in one a bronchoesophageal fistula and lung abscess developed, and two had severe persistent cough. All patients had a diagnostic barium esophagogram and endoscopy. Operation was performed in 17 patients, whereas three others declined operation. There was one hospital death. Follow-up is complete on 17 of 19 patients until June 1991. All operative survivors but one are free of symptoms. Of three patients refusing operation, one died of aspiration pneumonia, another died of myocardial infarction, and one with severe dysphagia is living. Because of the prevalence of aspiration (45%) and the potential for life-threatening pulmonary complications in some patients (15%), we conclude that operative intervention should be undertaken in all patients with thoracic esophageal diverticula regardless of the presence or absence of symptoms.

Adolescent↗

Stability of meropenem and effect of 1 beta-methyl substitution on its stability in the presence of renal dehydropeptidase I.

The stability of meropenem in the presence of renal dehydropeptidase I (DHP-I) varied extremely with the animal source of the enzyme. Meropenem, compared with imipenem, was rather easily hydrolyzed by DHP-Is from mice, rabbits, and monkeys, while it showed a higher resistance to guinea pig and beagle dog DHP-Is. In addition, meropenem was four times more resistant than imipenem to human DHP-I. The 1 beta-methyl substituent on carbapenems, i.e., meropenem and 1 beta-methyl imipenem, made them considerably more resistant to mouse and swine DHP-Is than the 1-unsubstituted derivatives are.

Animals↗

Synthetic studies of carbapenem and penem antibiotics. II. Synthesis of 3-acetyl-2-azetidinones by (2 + 2) cycloaddition of diketene and Schiff bases.

It was found that (2 + 2) cycloaddition reaction of diketene with Schiff bases was effectively promoted by imidazole as a catalyst to afford 3-acetyl-2-azetidinone derivatives 4. As an application of this new method, a practical asymmetric synthesis of 4 and its conversion into (3S,4S)-4-carboxy-1-(di-p-anisylmethyl)-3-[(R)-1-hydroxyethyl]-2- azetidinone, which is a key intermediate for the synthesis of carbapenem and penem antibiotics, were accomplished.

Anti-Bacterial Agents↗

Synthetic studies of carbapenem and penem antibiotics. III. A synthesis of a key intermediate for 1 beta-methylcarbapenem.

We synthesized useful intermediates 5 and 6 for 1 beta- and 1 alpha-methylcarbapenems from 4-carboxy-3-[(R)-1-hydroxyethyl]-2-azetidinone 4 as a starting material by using stereoselective hydrogenation and hydroboration, respectively. A practical synthetic route from 4 to the (3S,4S)-4-[(R)-1-carboxyethyl]-3-[(R)-1-hydroxyethyl]-2-azetidinone derivative 1, a useful intermediate for the synthesis of 1 beta-methylcarbapenem antibiotics, was established.

Anti-Bacterial Agents↗

New penem compounds with 5'-substituted pyrrolidinylthio group as a C-2 side chain; comparison of their biological properties with those of carbapenem compounds.

A series of new penem compounds with a C-2 side chain consisting of a pyrrolidin-3'-ylthio group substituted with various aminocarbonyl groups at the C-5' position have been prepared. Antibacterial activity, stability to renal dehydropeptidase-I and affinity to penicillin-binding proteins of these compounds were investigated and compared with the corresponding carbapenem compounds.

Anti-Bacterial Agents↗

Synthesis and biological properties of 1 beta-methylcarbapenems with N-methylpyrrolidinylthio group at C-2 position.

A series of 1 beta-methylcarbapenem compounds, which have a 5'-substituted-N-methylpyrrolidin-3'-ylthio group as a C-2 side chain, have been prepared and their biological properties were investigated. Substitution with a methyl group on the nitrogen atom in the C-2 side chain effectively enhanced stability to renal dehydropeptidase-I as well as introduction of methylene spacer between the aminocarbonyl group and the pyrrolidine ring of the 5'-aminocarbonylpyrrolidin-3'-ylthio group.

Bacteria↗

Subrenal capsule assay as a chemosensitivity test for primary esophageal squamous cell carcinoma.

The efficiency of the subrenal capsule assay (SRCA) was studied with fresh tissue of esophageal squamous cell carcinoma. The day-to-day changes in 10 carcinoma cases were evaluated for 9 days. The cancer cells continued to proliferate from the 3rd to the 7th day after the implantation and then decreased. The host reaction was recognized histologically from the 3rd or 4th day to the 9th day. However, the immune reaction did not significantly influence the evaluation of SRCA until the 7th day. The immunohistochemical staining with anti-bromodeoxyuridine monoclonal antibody revealed the existence of cancer cells at the DNA synthesizing stage (S stage) in the graft until the 7th day. In chemosensitivity test by SRCA, 21 patients were studied, and all were evaluable. 5-FU administration produced a response in 8/21 cases (38.1%), VDS in 8/21 (38.1%), and CDDP in 3/21 (14.3%). Used in combination, CDDP + VDS was effective in 7/18 cases (38.9%) and CDDP + BLM in 6/18 cases (33.3%).

Aged↗

High-grade dysplasia in the columnar-lined esophagus.

Abnormal columnar lining of the esophagus is a well-recognized premalignant condition. The management of patients with high-grade dysplasia without evidence of carcinoma remains controversial. Esophagectomy is proposed by some investigators, whereas others favor follow-up endoscopy and biopsy until microinvasive malignancy is documented. We reviewed our experience with nine patients referred with high-grade dysplasia on endoscopic biopsies without evidence of carcinoma. Eight patients had the columnar lining extending orad from the cardia, and one patient had heterotopic columnar epithelium in the cervical esophagus. All were white men ranging in age from 19 to 76 years (median: 47 years). Eight patients underwent esophagectomy with colon interposition. A sleeve resection of the cervical esophagus was done in one patient. Multifocal carcinoma was found in three patients, all of whom had severe dysplastic changes throughout the columnar lining. The patient with heterotopic columnar epithelium had microinvasive carcinoma. All four patients with carcinoma had negative nodes and are long-term survivors. No carcinoma was found in the resected specimens of the remaining five patients. High-grade dysplasia is an important marker of malignancy in patients with a columnar-lined esophagus. Esophagectomy is indicated in suitable candidates since carcinoma was found in 45% of our patients.

Adult↗

[Diversity of complement activation by lentinan, an antitumor polysaccharide, in gastric cancer patients].

Lentinan, a pure polysaccharide, augments many immune responses in vivo but not in vitro. Therefore reaction with any factor is thought to be required for triggering of immunopotentiation by lentinan. To clarify the role of complement in this effect, we investigated whether lentinan could activate alternative pathway of complement or not and the relation with the immunopotentiation in 13 gastric cancer patients. C3, C3a, C5 and C5a levels as parameters of complement activation and interleukin-2 producing activity as parameter of immunopotentiation were assayed before and immediately after intravenous injection of lentinan. Among these complement components, remarkable change was observed only in C3a level. C3a level elevated to more than 1000ng/ml from less than 300ng/ml. And according to the degree and continuation of the elevation, these patients were classified into 3 types-(1) every time little elevation, (2) first remarkable and thereafter little elevation and (3) continuous remarkable elevation. Such an elevated C3a level returned to the level before lentinan injection within one day. When C3a level elevated to more than 1000ng/ml, leukocyte counts of peripheral blood decreased significantly and interleukin-2 producing activity increased concomitantly. Thus, there was diversity in response to lentinan and complement activation was suggested to have contribution in immunopotentiation by lentinan.

Adjuvants, Immunologic↗

A novel carbapenem antibiotic, SM-7338 structure-activity relationships.

A series of new carbapenem compounds, which have a pyrrolidin-3'-ylthio group substituted with various aminocarbonyl group at C-5' position as C-2 side chain, have been prepared. The antibacterial activity and the stability to renal dehydropeptidase-I of these compounds were investigated, and the structure-activity relationships were discussed. In this series, SM-7338; (1R,5S,6S)-2-[(3S,5S)-5-dimethylaminocarbonylpyrrolidin-3-ylthi o]-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid (5a) was the most interesting compound.

Bacteria↗

Results of surgery in patients with gastric cancer extending to the adjacent organs.

Of 1,211 gastric cancer patients who underwent operations, 196 (16%) had cancers extending to the adjacent organs. Palliative procedures were performed in 66 (34%), and gastrectomies in 130 (66%). Operative mortality for the former was 6% (4/66), but was 0% for the latter. Among 130 gastrectomized patients 91 (70%) underwent combined resections of the invaded organs. With respect to the mean survival, significant differences were noted between gastrectomized (18 months) and non-gastrectomized patients (4 months), between the patients with (20 months) and without (12 months) combined resections, and between curative (27 months) and non-curative resections (13 months). Presence or absence, and degree of peritoneal, liver and lymph node metastases were also prognostic among gastrectomized patients. Combined resections of the involved organs showed slight, but positive, effects on survival of patients with liver metastases, but they seemed to be ineffective in the presence of peritoneal metastases. In the case of patients with apparently incurable factors such as P2-3, H2-3 or N4, gastrectomy was prognostically ineffective.

Colonic Neoplasms↗

Cloning and sequencing of the gene encoding the 72-kilodalton dehydrogenase subunit of alcohol dehydrogenase from Acetobacter aceti.

A genomic library of Acetobacter aceti DNA was constructed by using a broad-host-range cosmid vector. Complementation of a spontaneous alcohol dehydrogenase-deficient mutant resulted in the isolation of a plasmid designated pAA701. Subcloning and deletion analysis of pAA701 limited the region that complemented the deficiency in alcohol dehydrogenase activity of the mutant. The nucleotide sequence of this region was determined and showed that this region contained the full structural gene for the 72-kilodalton dehydrogenase subunit of the alcohol dehydrogenase enzyme complex. The predicted amino acid sequence of the gene showed homology with sequences of methanol dehydrogenase structural genes of Paracoccus denitrificans and Methylobacterium organophilum.

Acetobacter↗

[Prognostic factors in gastric cancer with serosal invasion--importance of the extent of cancer infiltration in the subserosal layer].

The extent of cancer infiltration in the subserosal layer has been examined in 214 stomachs resected for cancer with a serosal invasion. The extent was 4 cm or less in 109 patients (Group A) and 5 cm or more in 105 patients (Group B). The resection was estimated as being non-curative in 26% of Group A and in 52% of Group B (p less than 0.001). Peritoneal dissemination was the outstanding non-curative factor in the latter. The five-year survival rate was 39% in Group A and 14% in Group B (p less than 0.001). The survival rate after the curative resection was 49% and 26%, respectively (p less than 0.01). In Group B, peritoneal dissemination was the main mode of recurrence after the curative resection.

Adult↗

[Clinico-pathological study on recurrent gastric cancer after curative resection].

Among 675 patients who had undergone curative resection of gastric cancer during last 13 years, 113 died of cancer recurrence. One hundred and forty-five patients who had survived longer than 5 years were used as controls. In the recurrence group, the primary lesion was larger and the lymph node metastasis more common as compared with the surviving controls. Moreover, these lesions were often located at the upper third of the stomach and exhibited Borrmann 3 or 4 type. Prognostic serosal invasion was positive in 75 per cent of the recurrence group and negative in 84 per cent of the surviving controls. The most frequent mode of recurrence was hematogenous metastasis in negative prognostic serosal invasion (54%) and peritoneal disseminated metastasis in positive prognostic serosal invasion (52%). There were no differences in the distribution of gross and histological types of cancer in the modes of recurrence. It was found that peritoneal dissemination and/or local recurrence dominated as the mode of recurrence (51%), followed by hematogenous metastasis (34%), but that lymph node recurrence was uncommon (15%). In peritoneal disseminated cases, long-term survival following reoperation should not be expected. It was suggested that in order to improve the prognosis in the case of hematogenous metastasis, postoperative immunochemotherapy should be applied.

Adenocarcinoma↗

[Clinical evaluation of adjuvant radiotherapy and chemotherapy for esophageal carcinoma].

Surgical treatment is the most effective therapy for esophageal carcinoma, and adjuvant radiotherapy and chemotherapy are essential for the improvement of postoperative curability. The recurrence of carcinoma after curative surgery is often observed in the upper mediastinum and cervical portion. Fifty Gy of postoperative prophylactic irradiation has been given routinely and this has suppressed the local recurrence of the disease to a remarkable degree. Metastasis of carcinoma to internal organs was not controlled by radiotherapy. This occurs in the case of undifferentiated carcinoma, severe lymph node metastasis and positive invasion to vessels. Cisplatin, vindesine and bleomycin (DVB) combination chemotherapy and another cisplatin-based chemotherapy have been adapted for postoperative cases such as those in stages II, III and IV with radiotherapy. Cases of stage 0 and I with positive carcinomatous invasion to vessels have been treated reasonably with anti-cancer agents. Before chemotherapy, the anti-cancer activities of the drugs in subrenal capsule assay (SRCA) are tested using resected tumors and prospective clinical trials are being performed.

Animals↗

Prognostic factors of early gastric cancer--results of long-term follow-up and analysis of recurrent cases.

The prognosis of early gastric cancer (EGC) is generally excellent, however, EGC is not an exception to recurrence. In order to know what type of EGC is liable to recur, long-term results were studied in 304 cases of resection. The cumulative 10-year survival rate was poorer in patients with positive lymph nodes than in those with negative nodes (52.8 +/- 15.8 per cent vs 94.1 +/- 2.4 per cent; p less than 0.05). It was also less favorable when the EGC was greater than 5 cm in diameter (61.5 +/- 13.2 per cent vs 92.9 +/- 2.4 per cent; p less than 0.05). Among 50 cases which died postoperatively, six deaths were due to recurrence. A predominant mode of recurrence was hematogenous metastasis (4/6). The characteristics of EGC which recurred later included large cancer (greater than or equal to 5 cm) (6/6), macroscopically combined-type cancer (5/6), cancer of depth invasion to the submucosa (4/6) and histologically differentiated cancer (6/6). Lymph node dissection was not carried out in two of these patients at their primary operation. Adjuvant therapy should be added in the EGC bearing risk factors depicted above. Primary cancer in other organs, either metachronous or synchronous, was found in 13 cases (4.3 per cent). Colonic cancer, in particular, was seen in three, and it was 4.8 times as frequent as the expected number of the general population, calculated using the person-year method.

Adenocarcinoma↗