The minimum alveolar concentration of sevoflurane in cats

Eight adult cats of either sex were studied. The minimal alveolar concentration (MAC) for sevoflurane in the cats was found to be 2.58 ± 0.30% (mean ± SD). The ratios of MAC values between sevoflurane and halothane, enflurane and isoflurane in cats were very similar to those ratios found in humans and dogs. This observation suggests that the results of this study are correct and allows us to estimate unknown MAC values for sevoflurane in other species using known MAC values for other anesthetic agents.(Doi M, Yunoki H, Ikeda K: The minimum alveolar concentration of sevoflurane in cats. J Anesth 2: 113–114, 1988)     

Serum interleukin 6 levels become elevated in acute myocardial infarction.

We have examined serum interleukin 6 (IL-6) levels in 12 patients with acute myocardial infarction (AMI). IL-6 levels became elevated in all patients, following the rise of serum creatine kinase (CK) activity. Peak IL-6 levels showed a good correlation with peak serum C-reactive protein (CRP) levels, while there was no direct relationship between peak IL-6 levels and peak CK activity. IL-6 mRNA was not detected in unstimulated "quiescent" rat cardiocytes cultured in serum-free medium, but its expression was induced by exposure of the cells to serum or ionomycin. These results show that IL-6 is synthesized in the myocardium and serum IL-6 levels become elevated in AMI, suggesting that IL-6 could affect the progression and/or healing processes of AMI.     

Adriamycin-Lipiodol suspension for i. a. chemotherapy of hepatocellular carcinoma

Summary Physicochemical properties of two types of adriamycin preparation, suspensions and emulsions prepared for i.a. chemotherapy of hepatocellular cacinoma, were investigated. A suspension was prepared by dispersing adriamycin directly into the lipid contrast medium, Lipiodol, whereas an emulsion was obtained by emulsifying an aqueous solution of adriamycin into Lipiodol. The dispersibility of the drug in each preparation was examined microscopically. The chemical stability of and drug release from the preparation were determined by high-performance liquid chromatography and spectrophotometry, respectively. The suspension was then given to ten patients with primary hepatocellular carcinoma. The suspension maintained good dispersibility without coagulation of drug particles, whereas coalescence of aqueous droplets and the resultant phase separation occurred 4 h after preparation of the emulsion. Both preparations maintained the initial drug content for at least 1 week at room temperature. The release of adriamycin was more prolonged in the suspension than in the emulsion. After i.a. administration of the suspension, a selective accumulation of Lipiodol in the tumor and decrease in serum -fetoprotein (AFP) levels were found in most patients. A significant amount of adriamycin was still detected in hepatic speciments resected from two patients 1 and 2 months after treatment. These findings suggest that the adriamycin-Lipiodol suspension may be a useful preparation for targeting chemotherapy to hepatocellular carcinoma.     

Isolation and Structure Elucidation of Neokadsuranic Acid A, the First Triterpenoid with the 14 (13-->12) abeo Lanostane Skeleton, and (24Z)-3-Oxo-lanosta-8,24-dien-26-oic Acid1

Neokadsuranic acid A, which is the first triterpenoid with the 14(13-->12) ABEO lanostane skeleton, was isolated from KADSURA HETEROCLITA together with (24 Z)-3-oxo-lanosta-8,24-dien-26-oic acid. The present paper deals with the isolation and structure elucidation of these two new compounds.     

Population study of expression of thymidylate synthase and dihydropyrimidine dehydrogenase in patients with solid tumors

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) has been suggested to be sensitivity-limiting factors of 5-fluorouracil therapy in cancer patients. We conducted a large-scale population study on the activity of TS and DPD in patients with various solid tumors. A total of 2590 clinically removed tumors, consisting of 1112 colon, 724 gastric, 520 breast, and 236 non-small cell lung cancers, were provided to measure TS and DPD activity. TS activity in the gastric, colon, and non-small cell lung cancers was significantly higher than in matched non-cancerous tissue (P<0.0002), but there was no difference in TS expression between tumor and non-cancerous tissue from breast cancer patients. Gastric, breast, and non-small cell lung cancers showed significantly higher DPD activity than their corresponding non-cancerous tissues, but colon cancers did not. There was no correlation between TS activity and DPD activity, and thus each enzyme was considered to be an independent sensitivity-limiting factor for 5-fluorouracil therapy. The median TS activity and median DPD activity in all specimens including gastric, colorectal, breast, and non-small cell lung cancers tested were 0.041 and 110.1 pmol/mg protein, respectively. We classified each of the type of carcinoma into 4 groups by using the median activity of TS and DPD as the cutoff values: a low TS/low DPD group, high TS/low DPD group, low TS/high DPD group, and high TS/high DPD group. About 50% of the gastric, 47% of the colon, 70% of the breast and 30% of the non-small cell lung cancers had high TS activity, and 60% of the gastric, 40% of the colon, 48% of the breast, and 87% of the lung cancers had high DPD activity. Moreover, breast cancer was characterized by high TS activity and lung cancer by high DPD activity as compared with gastric and colon cancers, and their high activity levels may influence to the effectiveness of 5-fluorouracil against cancers of these organs. The results for expression of TS and DPD in clinically dissected tumors would be useful to estimate the efficacy of 5-fluorouracil in the treatment of cancer patients.     

Ultrastructure of early phase hepatic metastasis of human colon carcinoma cells with special reference to desmosomal junctions with hepatocytes

To demonstrate ultrastructural events in the early phase of hepatic metastasis of human colon carcinoma, we intrasplenically injected a highly metastasizable, human colon carcinoma cell line LM-H3 (1 x 10(6) cells) into nude mice, and electron microscopically investigated the hepatic metastasis. At 24 h, tumor cells adhered to the endothelial wall of terminal portal venules and periportal sinusoids. At 48-72 h, after extravasation, they deeply invaded the hepatic cell plate and the interstitial tissue of the portal tract, in which they underwent proliferation and made the metastatic foci. Tumor cells were linked with each other or with surrounding hepatocytes by desmosomes. Desmosomes were maintained during the mitosis. When invading tumor cells were exposed to the bile canaliculi, they generated microvilli on the surface. Microvilli were also formed at the luminal surface of intracytoplasmic inclusions. In the interstitial tissue of the portal tract, tumor cells were closely associated with fibroblasts. However, no junctional specializations were seen between them. The present study demonstrated that human colon carcinoma cell line LM-H3 formed desmosomes with hepatocytes soon after invasion of the hepatic cell plate, suggesting the regulatory role of an interaction with hepatocytes in the growth of metastatic foci within the liver parenchyma.     

Analysis of the butyrylcholinesterase gene and nearby chromosome 3 markers in Alzheimer disease

The K-variant of butyrylcholinesterase (BCHE-K) recently has been reported to be associated with Alzheimer disease (AD) in carriers of the epsilon4 allele of the apolipoprotein E (APOE) gene. We have re- examined the frequency of the BCHE-K allele in a large data set of both sporadic and familial cases of AD disease, and we have also examined the segregation of three genetic markers on chromosome 3 near BCHE . Our data neither support an association of BCHE-K with sporadic or familial AD, nor do they suggest the existence of another gene nearby on chromosome 3 as a common cause of familial AD.      

Effects of recombinant human endostatin on a human neuroblastoma xenograft

New antitumor agents must be added to the current neuroblastoma treatment regimens to improve the clinical results. We investigated whether recombinant human endostatin (rhEndostatin), an antiangiogenic agent, is effective against human neuroblastoma in the human neuroblastoma xenograft model designated TNB9. When tumors on the back of nude mice grew to a weight of 90-95 mg, rhEndostatin 10 mg/kg/day was administered subcutaneously every day for 10 consecutive days. Mean relative tumor weight in mice administered rhEndostatin (n=5) was significantly less than that in controls (n=12) on days 2, 4, and 6 after the start of administration (p<0.01 on day 2, p<0.05 on days 4 and 6), and regression of tumor growth (TRW<1.0) was marked on day 2. The maximum inhibition rate (MIR) by rhEndostatin was 46.4%, indicating inefficacy, but it may not be appropriate to apply Battelle Columbus Laboratories criteria to this experimental model because rhEndostatin is a protein. After day 8, tumors in the experimental group increased in weight and were not statistically significantly different from those in controls. Recombinant human endostatin was used in tumors in the arterial system of the mouse in this experiment because eventually rhEndostatin, not recombinant mouse endostatin, may be used to treat advanced neuroblastoma in the clinical setting. The results show that there is little cross-reactivity of rhEndostatin with the human and mouse models and indicate that rhEndostatin could become an effective agent for the treatment of human neuroblastoma.     

Immunohistochemical localization of the secretory products of rat Clara cells

We used proteins in rat lung lavage fluid to successfully produce an antiserum against Clara cell secretory products. When used with the immunoperoxidase method, the antiserum specifically stained cells of the bronchiolar lining, which are morphologically consistent with Clara cells, as well as a few columnar cells in the bronchial and tracheal mucosa. B-5-fixed lung tissue furthermore demonstrated the immunoreactive layer over the bronchiolar epithelium. The alveolar and bronchial lining layers, on the other hand, were not immunoreactive, although a trace of granular immunoreactivity was seen in the latter. It was suggested that Clara cells produce and secrete some proteinaceous materials, which are mainly localized in the bronchiolar area after secretion and are seldom transferred into the alveolar lining layer. Our antibody cross-reacted with the Clara cells of mice, but not with those of hamsters, guinea pigs, rabbits, dogs, cats, monkeys, and man. The high degree of specificity of this antisera to Clara cells in formalin-fixed materials should make it a valuable tool for identifying Clara cell change in non-neoplastic lung pathology and in obtaining some insights into cell origin in neoplastic diseases.     

Effects of blockers of Ca2+ channels and other ion channels on in vitro excystment of Paragonimus ohirai metacercariae induced by sodium cholate

The inhibitory effects of various ion channel blockers were examined on in vitro excystment of Paragonimus ohirai metacercariae induced by a bile salt, sodium cholate. At a concentration of 10 µM, bepridil, a non-selective Ca²⁺ channel blocker, completely inhibited in vitro excystment, whereas TEA, lidocaine, and R(+)-IAA-94, channel blockers against K⁺, Na⁺ and Cl^– ions, respectively, benzamil, an Na⁺/H⁺ and Na⁺/Ca²⁺ ion exchanger blocker, and R(+)-DIOA, a [K⁺, Cl^–] cotransporter inhibitor, did not. Considering the previous result that Ca²⁺ ionophores are also efficient inducing factors for in vitro excystment of P. ohirai metacercariae and the present result, bile salts appear to induce the excystment of P. ohirai metacercariae through evoking the Ca²⁺ channels of target cells within the metacercarial juveniles.