Biomedical subjects
Publications and source records attributed to H Kuwano.
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Hyperthermia using a radiofrequency system with an endotract antenna, combined with irradiation and chemotherapy, was prescribed for patients with resectable (n = 62) and unresectable (n = 31) squamous cell carcinoma of the esophagus, admitted to the 2nd Department of Surgery, Kyushu University Hospital from 1978. The histopathological effectiveness, according to the Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esophagus, and the long-term results were compared between two groups of patients treated with hyperthermo-chemo-radiotherapy (HCR therapy) and those treated with chemo-radiotherapy but not hyperthermia (CR therapy). In the resected cases, preoperative HCR therapy resulted in a significantly higher histopathological effectiveness rate (66%) compared with that in cases treated by CR therapy (49%) (p less than 0.05). The five-year survival rates of patients with resectable carcinoma given preoperative HCR therapy or CR therapy were 43.2% and 14.7%, respectively, and the two-year survival rates of those with unresectable carcinoma were 15.5% and 1.2%, respectively. Thus, HCR therapy produced not only a significantly higher histopathological effectiveness rate but also a significantly longer survival without severe side effects. This treatment would contribute to improvement of the prognosis of patients with carcinoma of the esophagus.
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Hyperthermia combined with irradiation and chemotherapy was prescribed for patients with resectable or unresectable squamous cell carcinoma of the esophagus. The long term results were compared between two groups of patients; one group was treated with chemotherapy, radiotherapy and hyperthermia (HCR), and the other was treated with chemotherapy and radiotherapy, but not hyperthermia (CR). The five year survival rates of patients with resectable carcinoma, given preoperative HCR or CR, were 43.2 and 14.7 per cent, respectively; the difference was statistically significant (p less than 0.05). The two year survival rates of those with unresectable carcinoma and receiving HCR or CR were 15.5 and 1.2 per cent, respectively. In particular, for the patients classified as TNM Stages I and II, a significantly longer survival period was obtained with HCR. As severe side effects in patients given hyperthermia were nil, this treatment deserves serious consideration when treating patients with a malignant lesion of the esophagus.
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Biopsy tissues from a 68-year-old Japanese man with metastases to axillary lymph nodes of a recurrent esophageal carcinoma were adapted to cell culture conditions and a continuously growing tumor cell line was developed. Immunohistochemical staining revealed that these cells contained keratinous material and the electron microscopic study revealed the presence of tonofilaments. Thus, this line, designated the KSE-1 line, was considered to have originated from metastatic squamous cell carcinoma of the esophagus. This line has a binding content of 4.2 fmol/mg protein for the estrogen receptor and 2.2 fmol/mg protein for the testosterone receptor. By measurement of cell number and thymidine incorporation, the growth rate of this line was found to be moderately responsive to these hormones, being inhibited by estrogen and enhanced by testosterone at concentration levels between 10(-13) and 10(-8) and 10(-13) and 10(-6) mg/ml, respectively.
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A review of 222 cases of squamous cell carcinoma of the esophagus revealed 67 (30.2%) with intra-epithelial carcinoma, contiguous with the main lesion. The incidences of such lesions were 10.9% and 68.0% in those given and not given preoperative irradiation, respectively. The 222 tumors were grouped into five categories, according to depth of invasion of the main lesion, those restricted to the mucosa, submucosa, proper muscular layer, and those invading the adventitia and neighboring structures. The rates of occurrence of intra-epithelial carcinoma were 87.5, 65.0, 26.9, 18.8, and 17.7%, respectively. Of the 67 with intra-epithelial carcinoma, the incidences of both proximal and distal location of such lesions were 85.7% in mucosal carcinoma, 84.6% in submucosal carcinoma, 71.4% in cancer restricted to the proper muscular layer, 50.0% in cancer invading the adventitia, and 9.1% in cancer invading the neighboring structures. Intra-epithelial carcinoma may thus originate from field carcinomatous transformation rather than from an intra-epithelial spread of the main lesions. These observations also support the concept of the field origin of carcinogenesis in the esophagus.
Two cases of extremely rare aneurysms of peripheral portions of the AICA are reported with a review of the pertinent literature. According to reported surgical findings, nearly all of the aneurysms originated from arterial loops near the internal acoustic meatus. These aneurysms can therefore, cause the cerebellopontine angle syndrome, with or without subarachnoid hemorrhage.
The mechanism of preventing intestinal regurgitation by means of a telescoped intestinal valve has been investigated in this study. Ten telescoped intestinal valves were uniformly created in dogs. A tolerance test to barium reflux was performed before the animals were sacrificed 16 weeks postoperatively, which yielded various barium tolerance values. Statistical analysis revealed that the differences in barium tolerance values in the uniformly constructed valves were closely related to the proportion of the enteric plexuses which contained ganglion cells with normal shapes (r = 0.97, p less than 0.001) and their intestinal segment coverage (r = 0.94, p less than 0.001), but no correlation was found between barium tolerance and the thickness of the valvular musculature (r = 0.04) or the length of the artificial valve (r = 0.39). The results in this study suggest that the intact enteric plexuses play an important role in modulating the competency of the telescoped intestinal valve.
The effect of intragastric balloons as a noninvasive method for weight reduction was observed in nine castrated Yorkshire pigs. None of the animals lost weight. The appetites of the experimental animals were inhibited for only a short period of time. A significant dilatation of the stomach after balloon insertion was noted which resulted from increased food intake and obliterated the effect of the intragastric balloons. A long-standing lower blood glucose level played an important role in the increments in food intake and dilatation of the stomach. At the same time, ulceration was seen in 83.3 percent of the animals that received balloons. We conclude that intragastric balloon therapy may not be an effective approach for managing morbid obesity in human subjects.
An Na+,K+-ATPase inhibitor possessing inhibitory activity against the specific binding of ouabain to Na+,K+-ATPase has been purified from the plasma of acutely saline-infused hogs. The purification was performed by a combination of Amberlite XAD-2 adsorption chromatography and five steps of high-pressure liquid chromatography (HPLC). Fast atom bombardment mass and proton nuclear magnetic resonance (NMR) spectrometric studies identified the purified substance as lysophosphatidylcholine gamma-stearoyl (LPCS). The ouabain-displacing activity in plasma, due to this compound, increased with time during saline infusion. The maximal level reached was approximately 12 times higher than that in the pre-infusion plasma sample. Lysophosphatidylcholines (LPCs) containing myristoyl, palmitoyl and oleoyl groups were also inhibitory to Na+,K+-ATPase and ouabain-binding to the enzyme. These LPCs were effective at 100 mumol/l concentrations in attaining 50% inhibition of the enzyme activity and ouabain-binding activity of Na+,K+-ATPase. These results suggest that LPCs containing long chain fatty acids could play an important role as a Na+,K+-ATPase inhibitors under volume-expanded conditions.
Structure elucidations of chloropolysporins A, B and C were achieved mainly by chemical degradation studies. These components possessed the same pseudoaglycone in common and their structures were closely related to that of beta-avoparcin. The structures of chloropolysporins differ from that of beta-avoparcin in the presence of vancomycinic acid moiety instead of monodechlorovancomycinic acid moiety and glucose, not ristosaminylglucose, in its side chain. Chloropolysporin C was identified as derhamnosylchloropolysporin B based on its 1H NMR and mass spectral analysis and degradation studies. Two minor components, chloropolysporins D and E, were identified as the epimers of each of chloropolysporins B and C, respectively, based on their Cotton effects and retention times on reverse phase HPLC.
The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor-promoting phorbol diester, were determined with regard to the induction of esophageal cancer in Wistar rats following a low-dose initial administration of the esophageal carcinogen N-amyl-N-methylnitrosamine [(AMN) CAS: 13256-07-0]. The induction of esophageal cancer was enhanced by TPA given in drinking water after AMN administration; i.e., the incidence of developing esophageal cancers and the multiplicity (number of esophageal cancers per rat) were significantly higher in groups given TPA solution orally after an oral administration of AMN than in those given the AMN solution alone. The enhancement of carcinogenesis with TPA was not affected by the interval between the administration of AMN and the administration of TPA. However, pretreatment with TPA before AMN administration did not enhance the induction of esophageal cancer. Neoplasms were not detected in groups given only TPA or tap water. Because this approach is similar to the phenomenon of two-stage carcinogenesis in the skin, it should provide a meaningful experimental model for studying two-stage carcinogenesis in the esophagus.
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Cell nuclear deoxyribonucleic acid (DNA) content was microspectrophotometrically determined in biopsy specimens from 75 patients with squamous cell carcinoma of the esophagus. The relationships among DNA distribution patterns, pathohistologic features, and prognosis were investigated. In patients with a high hyperploid DNA content (type IV), there was a high frequency of lymph node metastasis and lymphatic invasion, as compared with those exhibiting the near diploid DNA content (type II). In the type IV group, 22 of 23 patients died within 2 years, whereas patients with type II had a good clinical course and the 5-year survival rate was 60%. The DNA distribution pattern, determined by a multivariate Cox model analysis, was one of independent and significant prognostic variables. As these findings suggest that the DNA distribution pattern reflects the malignant potentiality of the tumor, the preoperative determinations of the DNA pattern in biopsy specimens of the esophageal carcinoma should provide a valuable parameter for predicting the prognosis.
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The combined antitumor effects of local hyperthermia and a simultaneous injection of bleomycin suspended in sesame oil (BLM-sesame oil) into the proper hepatic artery were studied in a model of liver cancer in rabbits. Fourteen days after inoculation of VX2 carcinoma into the left anterior lobe, 107 rabbits were used for the experiments. Local hyperthermia of 43-47 degrees C for 20 minutes was administered directly to the liver tumor via a 915 MHz microwave. In a preliminary study, administration of sesame oil alone into the proper hepatic artery led to a peripheral hepatic artery embolization, as evidenced by microangiography, and to the inhibition of tumor growth. The tumor-bearing rabbits were placed into groups of six. The first group was treated with hyperthermia, the second with a saline solution of bleomycin given intra-arterially, the third with a combination of hyperthermia and a saline solution of bleomycin given intra-arterially, the fourth with BLM-sesame oil given intra-arterially, the fifth with a combination of hyperthermia and sesame oil given intra-arterially, and the sixth with a combination of hyperthermia and BLM-sesame oil given intra-arterially. Consequently, the concomitant application of hyperthermia and intra-arterial injection of sesame oil led to a prominent inhibition of tumor growth, as compared with each modality alone (P less than 0.001). The most significant effect was obtained in the case of a combination of hyperthermia and BLM-sesame oil, as compared with a combination of hyperthermia and sesame oil (P less than 0.001). Local hyperthermia concurrent with the blockage of blood flow supplying the tumor led to a prominent inhibition of tumor growth, and addition of bleomycin to this regimen had an even greater antitumor effect. Thus, a combination of hyperthermia and chemoembolization with BLM-sesame oil is an effective treatment for liver cancer, at least in rabbits.