Biomedical subjects
Publications and source records attributed to T Kamiyama.
The structure of tetrafibricin, a novel and potent fibrinogen receptor antagonist isolated from the culture broth of Streptomyces neyagawaensis NR0577, was determined. Tetrafibricin has a unique structure containing primary amine, conjugated tetraenoic acid, and polyhydroxy functionalities that is biosynthetically related to the polyene macrolide antibiotics.
We developed a new system to estimate liver volume using CT-scan images printed on the films. This device is composed of X-Plan360i (Ushikata Shokai, Tokyo) and personal computer. Thirty-five patients with hepatocellular carcinoma were estimated those liver volume before and 4 to 6 weeks after hepatic resection. The presumed liver volumes calculated preoperatively were significantly correlated with the weight of the resected specimen. The postoperative increasing rates of residual liver volume was regulated by resected liver volume ratio and severity of associated cirrhosis. Four cases which suffered from postoperative liver insufficiency showed the lower postoperative rates than the patients without liver insufficiency. Measurement of liver volume with this method is simple and promises to play an important role for evaluate hepatic reserve.
We studied the effect of adjuvant hepatic arterial chemotherapy with THP-adriamycin (THP) and carboplatin (CBDCA) in patients with hepatocellular carcinoma (HCC). Fifteen patients were treated by intraarterial infusion of THP 30 mg on the second and third week after hepatectomy. CBDCA 450 mg was further injected on the fourth week (group A). Intrahepatic arterial administration of the drug was carried out through the subcutaneously implanted reservoir; one to five courses of the protocol were performed (average 2 times). Transient leukocytopenia occurred in six cases, liver dysfunction in one case, duodenal ulcer in one case and occlusion of the catheter connected reservoir in three cases. Forty-two patients not treated with this protocol postoperatively were employed as historical control (group B). There were no significant differences between group A and B in operative procedures, tumor stage, clinical stage, tumor size and other histopathological findings including nuclear DNA ploidy pattern. The two-year cumulative disease-free survival rate was 78% in group A, which was significantly better than the 55% of group B (p < 0.05). It may be concluded that intrahepatic arterial chemotherapy using THP and CBDCA plays an important role to prevent recurrences of the tumor after hepatectomy in patients with HCC.
A mouse-adapted substrain was recovered from a severe combined immunodeficient (SCID) mouse inoculated with the Gray strain of Babesia microti. In contrast to the original Gray strain, infection with this substrain (Gray/mo strain) resulted in a high level of parasitemia for a long period in SCID and nude mice, whereas immunocompetent BALB/c mice controlled the infection. The infection profile with the Gray/mo strain was closer to that of human babesiosis than that with the original Gray strain, suggesting usefulness of this mouse model for immunological studies of babesial infection. No antibody activity was revealed in sera of the infected SCID and nude mice. Although strong antibody activity was shown in the sera of the recovered BALB/c mice, no protective activity was demonstrated by the immune serum. Adaptive transfer of thymocytes from the normal BALB/c mouse resulted in SCID and nude mice being able to control the infection, indicating that cell-mediated immunity played a major role in control of infection with B. microti. However, because the reconstituted mice also produced significant antibody titer, antibody remains a possibility for a supportive role in control of the infection.
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Mouse erythrocytes infected with Plasmodium berghei were incubated for a short period in microplate wells. The parasites changed morphologically from the immature ring form to mature schizonts, and free merozoites were released. However, reinvasion of the erythrocytes appeared not to be possible in this system. This intraerythrocytic one-step growth of the parasite could be determined quantitatively by counting incorporation of 3H-hypoxanthine. The incorporation was markedly decreased by addition of certain antiparasitic agents to the culture. The sensitivity of this growth inhibition test was comparable to or higher than the mouse protection test. The results suggested the practical utility of this simple assay in screening antimalarial activity.
Since we have observed that acetaldehyde, an oxidative metabolite of ethanol, inhibits acetaminophen activation in rat liver microsomes, the in vivo effect of acetaldehyde on acetaminophen hepatotoxicity was tested. In vivo experiments in 3-methylcholanthrene-pretreated male Sprague-Dawley rats showed that administration of cyanamide (20 mg/kg, i.p.) and acetaldehyde (600 mg/kg, s.c.) given 3 and 1 h, respectively, prior to acetaminophen (500 mg/kg, i.p.) but not cyanamide alone prevented acetaminophen hepatotoxicity as assessed by serum transaminases and histology. Acetaldehyde may partly be responsible for the inhibitory effect of ethanol on acetaminophen hepatotoxicity.
1. The effects of caffeine on the NADPH-dependent production of paracetamol-glutathione conjugate were studied in rat and mouse liver microsomes. 2. In the presence of caffeine, glutathione conjugate production in rat microsomes was enhanced, whereas that in mouse microsomes was not affected significantly, showing an apparent species difference. 3. The data partly explain the species difference in the effects of caffeine on paracetamol hepatotoxicity.
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Arterial infusion therapy with implantable reservoir was performed for forty-seven cases with unresectable hepatocellular carcinoma since 1986-1991. The one-year survival rate of cases of arterial infusion therapy with implantable reservoir was 50.6% and the 2-year survival rate was 37.8%. The survival rate was 51.4% and 32.2%, respectively, in the TAE cases for the same period. Considering the kinds of reservoirs used for HCC, the survival curve of 23 cases with double lumen reservoir showed a significantly better pattern than that of 24 cases with the usual single lumen reservoir (p less than 0.05). Cumulative usable rate of reservoir was 78.6% at one year, and 42.4% at two years (Kaplan-Meier method). Therapy after the reservoir was unusable, particularly with arterial obstruction by catheter, was restricted because arterial infusion therapy was impossible. It is considered very important to retain the hepatic artery because arterial infusion therapy is mainly for unresectable hepatocellular carcinoma.
Nucleus DNA ploidy analysis was performed by flow cytometry on 81 patients with hepatocellular carcinoma. DNA ploidy patterns were divided into two groups; diploid pattern and aneuploid pattern, which were estimated by the rate of the first peak channel on histograms. DNA aneuploidy significantly correlated with serum AFP level (p < 0.01), TNM stage (p < 0.01), and pathological findings: vp (p < 0.5), im (p < 0.01). The aneuploid cases showed better prognosis than the diploid cases (Generalized-Wilcoxon test, p < 0.01). In the diploid cases, recurrent tumors manifested almost solitary isolated. The disease free period after hepatectomy was longer in diploid cases (mean 24.2 months) than in aneuploid cases (mean 14.4 months). There was a higher frequency of aneuploid cases of recurrence within 2 years compared to diploid cases. Two and half year survival rates after recurrence of diploid cases (69.6%) was significantly better than those of aneuploid cases (38.2%) (p < 0.05). The DNA ploidy pattern of hepatocellular carcinoma plays an important role in predicting the malignant potentials of the disease.
Liver resections for 52 cases with small hepatocellular carcinoma (HCC) less than 3cm in diameter were clinically studied. The 5-year-survival rate was 57.1%, which was better than that of percutaneous ethanol injection (PEI) therapy. Histological study revealed infiltration to the capsule in 48.1%, of which 20% had extra-capsular invasion. This finding seemed to be an important problem in PEI therapy. The group in which resected area was much larger than the extent of tumors had a tendency having good cumulative survival and non-recurrence rates. It is thought that the curative resection should be intended for small HCC if the patient has enough hepatic reserve to undertake a curative operation.
Red blood cells parasitized with Theileria sergenti were cultured in vitro for a short period in microplate wells. Addition of [3H]hypoxanthine to cultures enabled us to titrate the intraerythrocytic parasite growth because a significant amount of [3H]hypoxanthine was incorporated into the parasitized red blood cells (PRBC) in proportion to the number of PRBC. The incorporation of [3H]hypoxanthine was almost completed in an early phase of incubation. Bovine peripheral blood leukocytes incubated with lysate of PRBC did not incorporate [3H]hypoxanthine, indicating that contaminating leukocytes were not involved in the incorporation in the PRBC culture. The incorporation of [3H]hypoxanthine was decreased markedly by the addition of certain anti-parasitic drugs such as chloroquine, quinine, and pyrimethamine. This inhibition test was performed quantitatively with high sensitivity. Based on these results, this short-term culture seemed to be useful for drug screening or studying the mechanisms of theilerial infection. However, anti-T. sergenti antibodies failed to inhibit the [3H]hypoxanthine incorporation.
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Two cases of bizarre skeletal anomalies associated with intestinal malformation are presented. One patient had ileal atresia and Hirschsprung's disease, and the other anorectal malformation. Abnormalities in the number and morphology of ribs and vertebrae were present. Esophageal atresia often is associated with skeletal abnormalities, including supernumerary ribs, but these usually are not severe. Despite their severe costal malformations, neither patient had any complication after surgery to correct their intestinal malformation.
Two siblings with ileal atresia are described; one boy presented with ileal perforation and the other with meconium peritonitis, diagnosed by antenatal ultrasonography. The site and type of atresia, complications and associated anomalies of reported cases among siblings also are discussed.
A marked enhancement was seen in activities of mouse splenic natural killer (NK) cells and macrophages one week after infection with Mycoplasma pulmonis (Mp) or exposure to nitrogen dioxide (NO2). Macrophage activity of the Mp-infected mouse showed further augmentation by exposure to NO2 while NK activity of Mp-infected mice was not affected by NO2-exposure.
Four cases of advanced hepatocellular carcinoma patients were treated by intra-portal infusion of 5-FU immediately after surgery. 5-FU at 120-250 mg daily was injected continuously via portal catheter from postoperative day 4 to 21. Two cases with short administration period of 4 days died of recurrence on the residual liver at 9 and 7 months after hepatic resection. Another 2 cases with a total amount of 5-FU at 2,165 mg and 2,250 mg, respectively, survived 4 years 3 months and 4 year 8 months each. Mild leukocytopenia and transient liver dysfunction were found as side effects. Intraportal infusion of anticancer drugs is a promising means to prevent intrahepatic micrometastasis after resection of hepatocellular carcinoma.