Two cases of HTLV-I associated myelopathy (HAM) after cardiac operation

Sixty-one and 51-year-old males had progressive walk disturbance after cardiac operations at the intervals of 1 and 2 years. They had received blood transfusion at their operations. Physical examination revealed spastic paraparesis, sensory disturbance of the lower and rectobladder disorder. High titers of anti-Human T-lymphotrophic Virus type-I (HTLV-I) antibody were found in sera and CNF in both cases. They were diagnosed as HTLV-I associated myelopathy (HAM). Because they lived in Aichi Prefecture where the virus is non-epidemic, they were possibly infected through the blood transfusion at their operations. For prevention of HAM, the anti-HTLV-I antibody of all donor blood should be checked before transfusion.     

Elevated anti-alginate serum titers in patients with acute cholangitis and gallstones imbedded withPseudomonas aeruginosa

Electron microscopy and bacteriological culture revealed viable bacteria covered with a glycocalyx (biofilm) in choledochal stones recovered from two patients with acute cholangitis. On the cut surface of the choledochal stones, the cholesterol stone component was surrounded with a layer of brown pigment stone. In each case, bacterial culture of the choledochal stone recoveredPseudomonas aeruginosa. Since alginate is the main component of the glycocalyx produced byP. aeruginosa, serum IgM, IgG and IgA anti-alginate antibodies were measured in each patient. The present study is the first to demonstrate acute and transient IgM seroconversion to alginate in cases of acute cholangitis. In one case, the elevation of anti-alginate IgM preceded the elevation of anti-alginate IgG. The authors propose that the bacterial glycocalyx may play a significant role in acute cholangitis.     

Human leukocyte antigens in Fisher's syundrome

We performed human leukocyte antigens(HLA)typing for class I antigens on 19 Japanese patients with Fisher's syndrome. We demonstrated a statistically significant association between the disease and the HLA-B39 antigen.     

The effect of human SOD on the survival rate in rats with temporary splanchnic ischemia

The accumulation of oxygen free radicals is reported to occur in the organs subjected to temporary ischemia followed by reperfusion, resulting in the fatal outcome of the animals. The effects of human SOD, a representative scavenger of oxygen free radicals, on the survival rates were investigated in the rats with temporary splanchnic ischemia. The temporary ischemia was induced by the occlusion of anterior mesenteric and celiac arteries for 30min under anesthesia. Prior and after treatment with 2mg/100g of human SOD, iv or sc, produced significant improvements in survival rates. Human SOD, cloned from human placenta DNA and expressed in microorganisms, has extreme homogeneity. The results suggest the possible introduction of human SOD into clinical field as an effective scavenger of oxygen free radicals.(Ogawa R, Bitoh H, Ohi Y: The effect of human SOD on the survival rate in rats with temporary splanchnic ischemia. J Anesth 2: 41–45, 1988)     

Clinical studies on the measurement of urinary tissue polypeptide antigen (TPA) levels using Prolifigen TPA kit "Daiichi"-II in urothelial cancers

We have investigated the clinical significance of urinary tissue polypeptide antigen (TPA) as a tumor marker for urothelial cancers. Urinary TPA levels were determined by the immunoradiometric assay of Prolifigen TPA Kit "Daiichi"-II in 486 healthy controls and 1835 patients with various diseases including 526 with urothelial cancers and 140 with prostatic cancer. The mean value of urinary TPA was 199 +/- 213 (1SD)U/1 in 486 healthy controls. 95% of them having a level below 600 U/l. Therefore, 600 U/l was applied as a cut-off level. Positive rates of urothelial cancers and reactivated prostatic cancer were 57.6% (148 of 248 cases) and 45.5% (5 of 11 cases) respectively. On the other hand, the false positive rate of most urological benign diseases was only about 20% except for the acute stage of urinary tract infections and upper urinary tract stones with hydronephrosis. There was no significant difference in the positive rate between urinary TPA level and urinary cytology in urothelial cancers. The combination of both tests raised the positive rate to 73.1%. Therefore, urinary TPA may be useful in the monitoring of urothelial cancers, and the combination of urinary TPA and urinary cytology may increase the diagnostic accuracy.     

Disposition and excretion of Irgasan® DP300 and its chlorinated derivatives in mice

The distributions of radioactivity were examined by whole body autoradiography and liquid scintillation spectrophotometry in male ddY mice following oral administration of tritium-labelled Irgasan^® DP300 (2,4,4-trichloro-2-hydroxydiphenyl ether) (I) and its three chlorinated derivatives; 2,3,4,4-tetrachloro-2-hydroxydiphenyl ether (II), 2,4,4,5-tetrachloro-2-hydroxydiphenyl ether (III) and 2,3,4,4,5-pentachloro-2-hydroxydiphenyl ether (IV). The autoradiograms at 6 or 24 hr showed that the radioactivity distributed in the gall, liver, lung, heart, and kidneys. Among these tissues the radioactivity was most concentrated in the gall, suggesting the enterohepatic circulation of these compounds. A much higher level of radioactivity in each tissue was observed in mice receiving [³H]-III than the other compounds tested. Most of the radioactivity disappeared from each tissue in 24 hr due to [³H]-Irgasan DP300, [³H]-II or [³H]-IV, but in 96 hr it was due to [³H]-III.The cumulative radioactivity excreted in urine after administration of these compounds was in the order of [³H]-Irgasan DP300, [³H]-II, [³H]-IV and [³H]-III while that in feces was in the order of [³H]-IV, [³H]-III, [³H]-II and [³H]-Irgasan DP300,This work was presented at the 106th Annual Meeting of the Pharmaceutical Society of Japan (1986).     

A new HPLC fluorimetric method to monitor urinary delta-aminolevulinic acid (ALA-U) levels in workers exposed to lead

Summary A new sensitive HPLC method for the determination of urinary delta-aminolevulinic acid (ALA-U) was used to evaluate the relationship between blood-lead (Pb-B) and ALA-U levels in male workers exposed to lead. The differences between the ALA-U levels determined by this method (ALAU-HP) and by a colorimetric method (ALA-U-CL) are discussed. The HPLC method gave values similar to the ALA-U-CL values at high ALA-U level. However, at low blood-lead levels (58 ± 22 g/l, n = 23), the mean ALA-U-HP level corrected by urinary creatinine level was one-third of the corrected ALA-UCL level (0.83 ± 0.14 and 2.4 ± 0.5 mg/g creatinine, respectively). A significant increase of the mean corrected ALA-U-HP level was observed at 162 ± 22 g/l Pb-B (P < 0.05, n = 26), while that of ALA-UCL was observed at 245 ± 30 g/l Pb-B (P < 0.01, n = 37). The regression equation based on the logistic model fitted well to the relationship data between the Pb-B level and the percentage of the subjects with corrected ALA-U-HP above the cut-off point (1.12 mg/g creatinine) and the expected Pb-B level for 50% response was 270 g/l Pb-B, while it did not fit well to the relationship data between Pb-B level and the percentage of the subjects with corrected ALAU-CL above the cut-off point (3.5 mg/g creatinine). The maximum responses for the two sets of corrected ALA-U levels were both observed at 625 ± 25 g/l. The corrected ALA-U level by HPLC method seems to be a useful indicator for biological monitoring of exposure to lead at low levels (< 400 g/l Pb-B = health-based biological limit, WHO) as well as high ones.     

Polyclonal anti-desmosine antiserum is specific to desmosine molecule: no cross-reaction to pyridinoline

Inhibition ELISA assay was used to examine the cross-reaction of the polyclonal anti-desmosine antiserum produced in rabbit against molecules possessing a "pyridinium ring" as their core structure i.e. isodesmosine, pentasine, pyridinoline and 2'-deoxypyridinoline, highly purified with column chromatography, and structurally unrelated substances, i.e. cysteic acid, taurine and 2-aminopyridine (core structure of desmosine). No cross-reaction was observed to the pyridinoline, 2'-deoxypyridinoline possessing "pyridinium ring" and derived from collagen cross-links, structurally unrelated cysteic acid and taurine, nor core structure of 2-aminopyridine. The antiserum specifically recognized the molecules derived from the elastin cross-links. Using the ELISA assay system with antisera and amino acids analysis, 10 micrograms of desmosine were extracted from 1.0 mg of the hydrolysate of commercial elastin.     

Involvement of MMP-7 in invasion of pancreatic cancer cells through activation of the EGFR mediated MEK-ERK signal transduction pathway

AIMS: To clarify the involvement of matrix metalloproteinase-7 (MMP-7) in cell dissociation and the subsequent invasion of pancreatic cancer cells.METHODS: Western blotting, in vitro invasion assay, immunocytochemistry, and immunohistochemistry were performed in pancreatic cancer cell lines or pancreatic cancer tissue.RESULTS: The active form of the MMP-7 protein was expressed exclusively in the conditioned medium of dissociated (PC-1.0 and AsPC-1) pancreatic cancer cells, whereas proMMP-7 protein was only detected in the conditioned medium of non-dissociated (PC-1 and Capan-2) cells. Both intracellular and conditioned medium localised MMP-7 was greatly reduced by treatment with the epidermal growth factor receptor (EGFR) inhibitor AG1478 and the mitogen activated protein kinase kinase (MEK) inhibitor U0126 in pancreatic cancer cells. MMP-7 treatment significantly induced the disruption of tight junction (TJ) structures and subsequent cell dissociation, and activation of the EGFR mediated MEK- ERK (extracellular signal regulated protein kinase) signalling pathway in the non-dissociated pancreatic cancer cells. Moreover, the strong in vitro invasiveness of dissociated cells was inhibited by AG1478 and U0126 treatment, whereas the weak invasiveness of non-dissociated cells was apparently induced by MMP-7 treatment. In addition, MMP-7 expression was stronger at the invasive front than at the centre of human pancreatic tumours.CONCLUSION: MMP-7 is involved in cell dissociation and the subsequent invasion of pancreatic cancer cells. It induces the disruption of TJ structures and forms a positive feedback loop with activation of the EGFR mediated MEK-ERK signalling pathway.