Biomedical subjects

K Shindo

Publications and source records attributed to K Shindo.

255 records · Page 15Linked to original sources

PubMedDate not supplied

Hepatic arterial infusions of interleukin-2-based immunochemotherapy in the treatment of unresectable liver metastases from colorectal cancer.

In preclinical studies, hepatic arterial infusion of interleukin-2 (IL-2) in dogs significantly induced lymphocyte proliferation and augmented antitumor killing activity in the liver. Based on these findings, a pilot study of hepatic arterial infusions of IL-2-based immunochemotherapy was conducted in 21 patients (15 men, 6 women) with unresectable liver metastases from colorectal cancer, to determine whether the addition of IL-2 improved the therapeutic efficacy of chemotherapy alone. Interleukin-2 was given to all patients as 7 to 8 x 10(5) Japanese reference units (JRU) in addition to 5-fluorouracil (5-FU) 250 mg daily and mitomycin C (MMC) 4 mg once weekly, through a subcutaneous port for 3 weeks. After completion of the initial course, patients were discharged from the hospital and continued on a modified regimen for outpatient therapy: IL-2, 2.0 to 2.1 x 10(6) JRU and 5-FU 250 mg twice weekly; MMC 4 mg once weekly. Patient response rate was 76%, and the median survival from initiation of treatment was 24 months. Toxicity of the combined regimen was minimal. Peripheral lymphocyte phenotype study showed notable decreases in CD8+, CD16+, and CD57+ cells and an increase in CD4+ cells (ie, elevation of 4:8 ratio) during therapy. Electron microscopic analysis of the resected liver of a patient receiving the IL-2-mitomycin-C/5-fluorouracil (IL-2.MF) infusion showed a pronounced accumulation of lymphocytes, penetrating from the space of Disse, around the cancer cells. The present study explores hepatic arterial infusion of IL-2-based immunochemotherapy as a new strategy, based on the activation of liver-associated immune response; this technique may provide improved response and survival for unresectable liver metastases.

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PubMedDate not supplied

Autopsy findings in Down's syndrome with cerebrovascular disorder.

We describe the vascular pathologic findings in a 20-year-old Japanese man with Down's syndrome (DS) who developed stroke-like symptoms and died of respiratory failure attributed to a cerebral infarction. The latter was verified at autopsy, which also revealed vascular abnormalities resembling those of moyamoya disease. There were occlusions or stenosis in the bilateral internal carotid arteries, middle cerebral arteries, left posterior communicating artery, and basilar artery due to fibrous hypertrophy of the arterial intimal walls. The tunica media was highly atrophic and the internal elastic lamina was tortuous and duplicate. However, unlike moyamoya disease, main trunks of the cerebral arteries were of normal size, and there was marked stenosis of the basilar artery. These cerebrovascular abnormalities may have been the result of an immune deficiency, thrombosis, maldevelopment of the skull and brain, or may have been linked to moyamoya disease. Further study of similar cases is necessary to clarify the association between DS and moyamoya disease, as well as the pathogenesis of that disease.

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PubMedDate not supplied

Deconjugation ability of bacteria isolated from the jejunal fluid of patients with progressive systemic sclerosis and its gastric pH.

BACKGROUND/AIMS: Our goal was to demonstrate the role of bacteria in altered bile acid metabolism, which overgrow in the upper small intestine of patients with progressive systemic sclerosis. We identified the bacterial species, isolated from the jejunal fluid obtained from patients with progressive systemic sclerosis, who had previously shown an increase in 14CO2, specific activity on breath test, and normal controls. After which, we investigated the deconjugation ability of the isolated bacteria and the relationship between 14CO2, specific activity and gastric pH. METHODOLOGY: Bile acid breath tests were performed on 12 patients, and 19 normal controls using 5 microCi of oral glycine-1-(14)C-labeled glycocholate. Jejunal fluid was aspirated through a double lumen-tube with a rubber cover on the tip. Deconjugation ability was examined by thin-layer chromatography using conjugated bile acids in ox gall. RESULTS: The following species were identified in jejunal fluid samples obtained from patients: Bacteroides vulgatus, Eubacterium lentum, enterococcus, Lactobacillus bifidus, Escherichia (E) coli, Aerobacter (A) aerogenes. Except for E. coli and A. aerogenes, these species were capable of hydrolyzing conjugated bile acids in ox gall. The administration of chloramphenicol (1 g orally per day for 14 days in divided doses) significantly reduced the 14CO2, specific activity (p<0.05) in the patients with progressive systemic sclerosis. On the other hand, nineteen healthy control subjects demonstrated no increase in CO2 excretion, and 16 of the 19 had no bacteria isolated from jejunal fluid. The remaining healthy man showed an overgrowth of E. coli and Pseudomonas (P) aeruginosa, but the E. coli and P. aeruginosa did not have the ability of deconjugation. CO2 specific activity of expired breath samples in the patients with progressive systemic sclerosis was correlated with gastric pH (n=12, r=0.588, p<0.05). CONCLUSIONS: Our results demonstrated that some of the bacterial species that overgrow in the upper small intestine of patients with progressive systemic sclerosis can deconjugate bile acids, and that a shift to neutral pH in gastric juice, may promote the bacterial overgrowth related to their impaired peristaltic activity.

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