Clinical importance of serum anti-p53 antibodies as tumor markers

Anti-p53 antibodies are autoantibodies induced by mutation of p53 cancer-suppressor gene, and are considered to be indirect markers for p53 gene mutations and abnormally high p53 gene levels. We evaluated the usefulness of the measurement of anti-p53 antibodies by enzymed-linked immunosorbent assay using serum samples from patients with various disorders and normal subjects. The anti-p53 antibody concentration was high in patients with lung, esophageal, gastric, hepatocellular, colonic, rectal or ovarian cancer and significantly differed between the group with neoplasms and those with non-neoplastic disorders. Particularly high concentrations were observed in patients with malignant tumors. The mean agreement rate between anti-p53 antibodies and conventional tumor markers was only 47.8% despite slight differences among disorders. The positive rate increased to 63.0% by their combination assay. In addition, anti-p53 antibodies were independent markers, not complimentary to conventional markers. The mean agreement rate between anti-p53 antibodies and tissue p53 was 70.0%. Though the anti-p53 antibody-positive rate was lower than the tissue p53-positive rate, anti-p53 antibodies may be useful new tumor markers because specimens from the affected tissue are not necessary.     

Chronic myelogenous leukemia with a complex Ph1 translocation in an XYY male

We encountered a 38-year-old Japanese male patient with chronic myelogenous leukemia (CML), whose bone marrow and peripheral blood cells during the chronic and blastic phases contained a complex Ph¹ translocation and an extra Y chromosome [i.e., 47,XYY,t(9;22;13)(q34;q11;q14)]. A karyotypic analysis of PHA-stimulated lymphocytes showed the constitutional karyotype to be 47,XYY. Thus, it was considered that CML with a complex Ph¹ translocation developed in an XYY male; such a case has not been reported, so far. A B-lymphocyte cell line with the complex Ph¹ translocation was established by the procedure of Epstein-Barr virus transformation. The presence of the complex Ph¹ translocation in the B-lymphocyte cell line suggests that some of the B lymphocytes in this patient originated from the CML clone.     

Climatic adaptation in thermogenesis and thermal insulation in wood mice (Apodemus argenteus)

Wood mice (Apodemus argenteus) were trapped live at three different altitudes (below 1,000, 1,900, and 2,400 m) during a 1-year period (Feb. 1984-Jan. 1985). After remaining at the trapped locations for 10-14 days, they were transferred into a climatic chamber at an altitude of 610 m. Oxygen consumption (VO2) and colonic temperature (Tco) were measured at chamber temperatures (Ta) of five steps (30, 20, 10, 0, and -10 degrees C) in freely moving conditions. In response to Ta of 0 degrees C for the mice trapped in winter when their mean local habitat temperature (Te) were lower than 0 degrees C, there was a significant inverse correlation between VO2 and Te (r = -0.70, p less than 0.001) whereas no significant correlation (r = 0.23) was observed in the mice trapped in other seasons when Te was higher than 0 degrees C. The correlation between Tco and Te was significant (r = -0.66, p less than 0.001) over the entire range of Te. The pelt weight of the mice trapped at Te higher than 0 degrees C had a significant inverse correlation with Te (r = -0.65, p less than 0.001), but not in the mice trapped at Te lower than 0 degrees C. After measurement of VO2 and Tco at Ta of 0 degrees C, the mice who had lived in colder habitats (below 0 degrees C) showed 0% mortality, whereas the mortality of the populations which had lived in warmer habitats was 13%. These results suggest that, in wood mice, adaptation to severe cold is established by an enhanced thermogenesis and by an increased insulation of the pelt in moderate cold.     

Ia expression in chronic relapsing experimental allergic encephalomyelitis induced by long-term cultured T cell lines in mice

Chronic relapsing experimental allergic encephalomyelitis was induced in SJL mice by adoptive transfer of long-term cultured T cell lines. The T cells which were activated with myelin basic protein (MBP) derived from various species, all induced chronic relapsing experimental allergic encephalomyelitis with a similar high incidence. During the relapsing stage, lymphocytes obtained from the spleen responded well to MBP and were capable of transferring experimental allergic encephalomyelitis, whereas thymus lymphocytes did not respond to MBP. There was no difference in the proliferative response of splenocytes to MBP when splenocytes were isolated either from mice with clinical relapse or from mice that did not relapse. Pathological examination revealed a transient appearance of inflammatory cells during the acute stage. Similar cell infiltrates were also observed at the relapsing stage. The I-region associated (Ia) antigens appeared on vessels and astrocytes in the acute inflammatory lesions which coincided with the appearance of inflammatory cell infiltrates. Ia antigen expression diminished with the disappearance of inflammatory cells. During the relapsing stage, the Ia antigens were also expressed on the vessels and astrocytes in the fresh lesions. Our data indicate that MBP-reactive T cells persist at least in the spleen, for a long time. They may be reactivated by certain mechanisms probably in the central nervous system associated with the Ia-antigen expression, which facilitates the effector phase again. The initial event that triggers the Ia-expression is not known as yet.     

Non-adhesive cyanoacrylate as an embolic material for endovascular neurosurgery

Endovascular neurosurgery is now becoming available as one of strategies for the treatment of cerebro-spinal arterio-venous malformations and aneurysms. For this treatment, a microcatheter is advanced into or close to a lesion and then an embolic material is administered through it to obliterate the lesion. N-butyl-2-cyanoacrylate (NBCA) has preferentially been used as an embolic material in Europe and America. However, its exceptionally strong adhesive force sometimes causes adhesion between the tip of the microcatheter and the artery. In this study, a new non-adhesive cyanoacrylate, isostearyl-2-cyanoacrylate (ISCA), was developed. It carries a long hydrophobic side isostearyl group with lower reactivity and adhesion than other cyanoacrylates. Its polymerization rate is, however, too low to obliterate a vascular lesion with a rapid blood flow. To increase the polymerization rate. ISCA was mixed with NBCA. As a result, the adhesive force of the mixture became extremely low, compared with that of NBCA. The viscosity of the mixture was low enough to allow its' use as an embolic material. Tissue reactions against the mixture was milder than those against NBCA. Radio-angiography became possible by mixing further with Lipiodol. The evaluation of this new embolic material with a rabbit renal artery showed that the obliteration effect of the mixture of ISCA and NBCA was excellent to use as an embolic material for clinical applications.     

Increase of IgA specific helper T alpha cells in patients with IgA nephropathy.

Patients with IgA nephropathy show an emergence of IgA dominant circulating immune complexes (CIC) as well as increased levels of serum IgA and/or IgA bearing peripheral blood lymphocytes. In order to elucidate immunological aberrations responsible for the increased IgA synthesis in such patients, quantitative and qualitative analysis was performed on T alpha cells which have been recently identified as possessing IgA specific helper activity on human B cells. Three different methods were employed to quantitate T alpha cells. These methods included a rosette formation of T cells with either bovine red cells coated with the IgA fraction of anti-bovine red cell antiserum or those coated with TNP and anti-TNP IgA antibody, and an analysis of T cells combined with fluorescein conjugated human IgA myeloma protein. T alpha cells were sorted by a fluorescence activated cell sorter and co-cultured with a B cell rich fraction to evaluate whether there is a qualitative difference in IgA specific helper activity between patients and healthy adults. T alpha cells were significantly increased in patients with IgA nephropathy while there were no significant changes in patients with chronic proliferative glomerulonephritis without mesangial deposition of IgA. There was no qualitative difference in IgA specific helper activity of T alpha cells between patients and healthy adults. It is suggested that increased levels of T alpha cells in patients with IgA nephropathy may be responsible for increased synthesis of IgA in such patients.     

Effects of quercetin, a plant flavonol, on the two-stage transformation in vitro

Quercetin was examined for the effects on the two-stage chemical transformation of BALB/3T3 cells. Quercetin showed initiating action to induce transformation in the cells which were treated with quercetin and subsequently with 0.49 microM 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Both the proportion of dishes with transformed foci and the average number of foci per dish increased with the concentration of quercetin (15-45 microM). However, initiating treatment with quercetin did not induce transformation without subsequent TPA treatment. Quercetin inhibited the promotion caused by 0.49 microM TPA in the transformation initiated by 1.9 microM 2-methylcholanthrene (MCA). The inhibitory effect of 30 microM quercetin was 56% in the number of foci per dish. Thus quercetin was found to have initiating effect on the transformation of BALB/3T3 cells, but to restrain the promotion by TPA.     

Studies on the metabolic fate of 14C-rokitamycin. I. Absorption, distribution, metabolism and excretion in rats

Blood concentrations of 14C-rokitamycin (14C-TMS-19-Q) reached their peaks at 1 hour after a single oral (200 mg/kg) administration to male and female rats, and they were 28.0 +/- 0.8 and 24.9 +/- 2.0 micrograms/ml, respectively. No significant differences were observed between male and female in AUC values or maximum blood concentrations. The distribution of TMS-19-Q was good, and concentrations of 14C were high in liver, kidney, spleen, pancreas, adrenal, pituitary gland, thyroid, trachea, exorbital lacrimal gland, submaxillary gland and bone marrow. During the 72 hours period after a single oral (200 mg/kg) administration of 14C-TMS-19-Q to male rats, 8.0 and 89.6% of the dose were excreted in urine and feces, respectively and a total recovery rate was 97.5% of the dose. During the 48 hours period after a single intraduodenal (200 mg/kg) administration of 14C-TMS-19-Q in male rats, 6.9 and 36.2% of the dose were excreted in urine and bile, respectively. Reabsorption of 14C excreted from the bile was negligible. Absorptions of TMS-19-Q from the duodenum, jejunum, ileum and colon were good, but absorption from the stomach was negligible. Major metabolic reactions of TMS-19-Q were deacylation and hydroxylation, and the major metabolites in rats of TMS-19-Q found in the plasma, urine and bile after oral and intraduodenal administration were 10"-OH-TMS-19-Q, leucomycin A7, leucomycin V and 14-OH-leucomycin V.     

Correlation of paramesangial deposits and glomerular sclerosis and/or hyalinosis in patients with IgA nephropathy

Correlation of paramesangial deposits ("hemispherical body") and glomerular sclerosis and/or hyalinosis was examined by light microscopical analysis in 40 patients of IgA nephropathy. Correlation of paramesangial deposits and intensity of IgA or C3 deposition in glomeruli was also evaluated in these patients. The number of paramesangial deposits was markedly increased in patients with moderate and advanced stages of IgA nephropathy who showed marked glomerular sclerosis and/or hyalinosis. There was a significant correlation between the number of paramesangial deposits and the intensity of IgA deposits in glomeruli. It is suggested that the accumulation of paramesangial deposits might induce severe glomerular injuries such as glomerular sclerosis and/or hyalinosis.