Segmental hyperhidrosis in syringomyelia with Chiari malformation

Segmental hyperhidrosis was seen in three cases of syringomyelia with Chiari malformation confirmed by magnetic resonance imaging. Using the iodine starch reaction, all three cases showed hyperhidrosis in the areas roughly corresponding to those of sensory disturbances. Two possible modes of pathogenesis are discussed: stimulation of preganglionic neurons and interference to the inhibitory tract.     

Electrophysiological study on the atrophied pectoralis major muscle after modified radical mastectomy

In order to clarify the cause of the atrophy of the pectoral muscles after modified radical mastectomy, twenty patients who had had the operation at Nagasaki Chuo National Hospital 40 days to 2 years prior to this study, were investigated by electromyography. Of 20 subjects, 11 had the operation to preserve the pectoralis major muscle and 9 had the operation to preserve both the pectoralis major and minor muscles. The results were as follows: 1) Electromyography revealed some damages to the pectoral nerves in 16 cases of 20 (80%). In 12 cases, development of fibrillation potentials was observed at rest, while motor unit potentials disappeared during voluntary contraction. These findings suggest the damage to the nerves including neutrotomy. 2) The regions with macroscopic muscular atrophy remarkably coincided with those with neurogenic changes on electromyography. This suggests that the atrophy of the pectoralis major after modified radical mastectomy might be mainly caused by the damage to the pectoral nerves. 3) The mastectomy preserving only the pectoralis major tends to cause damage to nerves innervating the sternocostal part of the pectoralis major more frequently than the mastectomy preserving both the pectoralis major and minor muscles. The abdominal part was frequently damaged irrespective of the types of the operation.     

Antitumor activity and cellular accumulation of a new platinum complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platinum( II) monohydrate, in cisplatin-sensitive and -resistant murine P388 leukemia cells.

We have examined the cytotoxicity and accumulation of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R) in parent and cisplatin-resistant mouse P388 leukemia cells (P388 and P388/DDP), in comparison with those of cisplatin (CDDP) and carboplatin (CBDCA). The degrees of resistance to CDDP and CBDCA, expressed as the ratio of IC50 for P388/DDP cells to IC50 for P388 cells, were 75-33 and 100-27, respectively, under the conditions of 2-24 h exposure to each drug at a density of 10(6) cells/ml. The corresponding values (25-7) for DWA2114R were relatively low. Accumulations of CDDP and CBDCA were reduced in P388/DDP cells; however, no reduction in accumulation of DWA2114R was observed at various exposure periods and concentrations of the drugs. The accumulations of CDDP in P388 and P388/DDP cells at drug concentrations corresponding to the IC50 values for drug exposure periods of 2-24 h were 0.41-0.97 and 13.1-33.7 ng Pt/10(7) cells, respectively, suggesting that an intracellular mechanism of resistance against CDDP could be activated in P388/DDP cells. P388/DDP cells also showed relatively low resistance to DWA2114R via this mechanism in comparison with CDDP and CBDCA. From the relationship between structure and activity of several Pt-complexes, these different properties of DWA2114R compared with CDDP and CBDCA could be due not only to the differences in carrier ligand structure but also to the properties of the whole molecule associated with the carrier ligand and leaving group.     

Analysis of abnormal expression of g-csf gene in a novel tumor cell line (KHC 287) elaborating G-CSF, IL-1 and IL-6 with co-amplification of c-myc and c-ki-ras.

We established a human carcinoma cell line (KHC 287) from a patient with large-cell-typing lung carcinoma associated with marked leukocytosis. The culture supernatant of KHC 287 cells promoted granulocytic colony formation of human bone-marrow cells in semi-solid culture. Colony formation was almost completely suppressed by treatment of the supernatant with a monoclonal anti-granulocyte colony-stimulating factor (G-CSF) antibody. Not only G-CSF but also interleukin-1 alpha (IL-I alpha), IL-I beta and IL-6 were detected in the culture supernatant by an ELISA method. Northern blot analysis of KHC 287 cells revealed distinct expression of these cytokine genes. Southern blot hybridization of KHC 287 DNA showed 20- and 40-fold co-amplification of c-myc and c-ki-ras, respectively. The chloramphenicol acetyl transferase (CAT) activity was distinctly enhanced in the KHC 287 cells which were transfected with the 360 bp upstream region of G-CSF gene inserted into pSV00CAT, but not in non-G-CSF-producing tumor cell lines. These results suggest that overproduction of the transactivating factor(s) which binds to the 360 bp of the G-CSF upstream region is responsible for the abnormal expression of G-CSF gene in KHC 287 cell line.     

Species differences in zearalenone-reductase activity

Thin-layer and high-pressure liquid chromatography (HPLC) were used to investigate in several animal species the hepatic metabolites of zearalenone (ZEN), a non-steroidal oestrogenic fungal toxin produced by species of Fusarium. ZEN was reduced to zearalenol (ZEL) by the S-9 fraction of rat-liver homogenates in the presence of NADH or NADPH. In this species ZEN reductase showed two peaks of activity at pH 4.5 and 7.4. Of the species tested, cows showed the highest activity of NADH-dependent ZEN reductase in the hepatic S-9 fraction, followed in decreasing order by mice, pigs, rats, rabbits and guinea-pigs. The S-9 fraction of hamster liver showed optimal activity at pH 5.5 and 8.0 with NADH and at pH 6.0 and 8.5 with NADPH; NADPH was more efficient than NADH only in this species. HPLC showed that alpha-ZEL was a major hepatic metabolite in the rat, mouse, pig, cow and rabbit in incubations at pH 4.5 with either NADH or NADPH and at pH 7.4 with NADH, although at pH 7.4 with NADPH, beta-ZEL was the predominant metabolite. In guinea-pigs, both alpha- and beta-ZELs were produced in roughly similar amounts irrespective of the pH and cofactor, while in hamsters beta-ZEL was the major metabolite. These findings indicate that there are two types of ZEN reductase differing in optimum pH and that the stereospecific reduction of ZEN depends on the source of S-9 and cofactors. Since the oestrogenic activity of alpha-ZEL is about ten times greater than that of ZEN, the possible presence of ZEN metabolites in edible tissues of livestock fed on ZEN-contaminated feeds is an important mycotoxicological problem.     

Aminoglutethimide and aminoglutethimide+tamoxifen treatment for advanced breast cancer]

Twenty-eight and 24 patients with advanced breast cancer were treated with Aminoglutethimide (AG) or AG + Tamoxifen (AG + TAM) from June 1984 to June 1989, respectively. Evaluated cases were 25 and 21 treated with AG or AG+TAM, respectively. Objective response was seen in 5/25 (20.0%) for AG treatment with 9, 13, 16, 20 and 31 months remission and 4/21 (19.1%) for AG + TAM treatment with 6, 7, 12 and 26 months remission. Response rate according to dominant site of metastases were 1/10 in soft tissue, 2/7 in bone, 2/7 in lung and pleura treated with AG, 1/9 in soft tissue, and 3/5 in lung treated with AG + TAM treatment. Two of the 5 responding patients in AG treatment group had prior tamoxifen treatment and 3 out of 4 responding patients in AG + TAM treatment group had prior chemoendocrine therapy with tamoxifen and FAC chemotherapy. Main toxic side effects were lethargy and/or rash, and drug discontinuation was required in 3 cases of AG treatment group and 2 cases of AG + TAM treatment group. Serial determination of serum hormone levels during AG or AG + TAM treatment revealed a decrease in estrone and an increase in androstenedione in many cases of both treatment groups. This data suggested that AG treatment may be favorable for endocrine treatment for advanced breast cancer patients, but the response to AG was not augmented by adding TAM.     

Epigenetic inactivation of IkappaB Kinase-alpha in oral carcinomas and tumor progression.

PURPOSE: The loss of epithelial phenotypes in the process of carcinoma progression correlates with clinical outcome, and genetic/epigenetic changes accumulate aggressive clones toward uncurable disease. IkappaB kinase-alpha (IKKalpha) has a decisive role in the development of the skin and establishes keratinocyte phenotypes. We assessed clinical implications of IKKalpha expression in oral carcinomas and epigenetic aberrations for the loss of expression. EXPERIMENTAL DESIGN: We examined IKKalpha expression in oral carcinomas by immunostaining (n = 64) and genetic instability by microsatellite PCR (n = 46). Promoter methylation status was analyzed by bisulfite-modified sequence (n = 11). RESULTS: IKKalpha was expressed in the nucleus of basal cells of normal oral epithelium, but not or marginally detected in 32.8% of carcinomas. The immunoreactivity was significantly decreased in less differentiated carcinomas (P < 0.05) and correlated to long-term survival of patients (P < 0.01) with an independent prognostic value (P < 0.05). Although allelic/biallelic loss of the gene was limited to four cases, we detected microsatellite instability in 63.0% cases in which the immunoreactivities were decreased and the promoter was hypermethylated. CONCLUSION: These results showed that oral carcinomas exhibiting genetic instability and promoter hypermethylation down-regulate expression of IKK and suggest that the epigenetic loss of the expression closely associates with disease progression toward unfavorable prognosis.