A clinical study of 104 patients with tongue cancer and the relationship between DNA ploidy and prognosis in 41 cases

One-hundred and four patients with previously untreated tongue cancer seen in our department between 1986 and 1998 were enrolled in a clinical study. The DNA ploidy patterns observed in fresh frozen specimens obtained from 41 patients were analyzed, and prognostic factors were investigated. According to the TNM classification (UICC 1997), 43 patients had stage I tumors, 29 had stage II tumors, 17 had stage III tumors, and 15 had stage IV tumors. The 5-year cause-specific survival rates for each stage were 94.7%, 64.4%, 50.0% and 45.7%, respectively. The most frequent cause of death associated with the original disease was the recurrence of the disease in cervical lymph nodes (19/27, 70.4%). The occurrence of late cervical metastasis was high among patients with a T2N0 disease. Patients with stage II disease should undergo elective neck dissection or be carefully monitored using ultrasonography. Among the 41 cases in which the DNA ploidy pattern was analyzed, diploid patterns were found in 30 cases and aneuploid patterns were found in 11. The 5-year cause-specific survival rate and the 5-year locoregional control rate were significantly lower for the aneuploid cases (18.2%, 38.9%) than for the diploid cases (66.5%, 69.8%) (p = 0.0003, p = 0.0339). The incidence of distant metastasis was significantly higher among the aneuploid cases (6/11, 54.5%) than among the diploid cases (3/30, 10.0%) (p = 0.0058). The ploidy pattern, as determined by flow cytometric DNA analysis, may reflect the malignancy grade of tongue cancers.     

Effect of ultraviolet irradiation on the protein synthesis of human skin cells: a study with a monochromatic ultraviolet irradiation apparatus

Human beings always suffer from serious risk of exposure to ultraviolet (UV) rays in general as well as in work environments but the health effects of UV are not yet fully understood. To enable fine analysis of the biological effects of UV at any given wavelength, we developed an apparatus that can experimentally irradiate cultured mammalian cells with monochromatic UV rays at any given wavelength. With this device, the effects of UV at 260, 280, 300 and 320 nm on the total protein synthesis of human skin-derived NB1RGB cells were examined. An inhibitory effect of UV at 260 and 280 nm was evident, whereas UV at 300 and 320 nm had only a marginal effect. UV at 280 nm also decreased amino acid uptake, which appears, at least partly, to be responsible for reduced protein synthesis. Metallothioneins (MTs), known as proteins defending against heavy metal toxicity, have been reported to be induced after UV irradiation, but UV at 280 nm did not induce MTs in NB1RGB cells. Cadmium pretreatment of cells, that had been assumed to protect cells from UV damage via MT induction, did not increase cell viability after exposure to UV at 280 nm. The present study unambiguously revealed the biological effects of monochromatic UV rays, also showing that the UV-irradiating apparatus can be a powerful tool for studying the health effects of UV.     

Time-Dependent Oral Absorption Models

The plasma concentration–time profiles following oral administration of drugs are often irregular and cannot be interpreted easily with conventional models based on first- or zero-order absorption kinetics and lag time. Six new models were developed using a time-dependent absorption rate coefficient, k_a(t), wherein the time dependency was varied to account for the dynamic processes such as changes in fluid absorption or secretion, in absorption surface area, and in motility with time, in the gastrointestinal tract. In the present study, the plasma concentration profiles of propranolol obtained in human subjects following oral dosing were analyzed using the newly derived models based on mass balance and compared with the conventional models. Nonlinear regression analysis indicated that the conventional compartment model including lag time (CLAG model) could not predict the rapid initial increase in plasma concentration after dosing and the predicted C_max values were much lower than that observed. On the other hand, all models with the time-dependent absorption rate coefficient, k_a(t), were superior to the CLAG model in predicting plasma concentration profiles. Based on Akaike's Information Criterion (AIC), the fluid absorption model without lag time (FA model) exhibited the best overall fit to the data. The two-phase model including lag time, TPLAG model was also found to be a good model judging from the values of sum of squares. This model also described the irregular profiles of plasma concentration with time and frequently predicted C_max values satisfactorily. A comparison of the absorption rate profiles also suggested that the TPLAG model is better at prediction of irregular absorption kinetics than the FA model. In conclusion, the incorporation of a time-dependent absorption rate coefficient k_a(t) allows the prediction of nonlinear absorption characteristics in a more reliable manner.     

Micelle-mediated extraction for concentrating conjugated bilirubin in urine

An extraction method based on the phase separation of aqueous micellar solutions of n-octyl-beta-D-thioglucoside (OTG) was applied to the concentrating conjugated bilirubin in urine. The analyte in sample solutions could be efficiently concentrated into a small volume of surfactant-rich phase, while hydrophilic matrix components including urinary protein, ascorbic acid, and saccharide remained in the aqueous phase. The concentrated OTG negligibly affected the diazo reaction and the subsequent spectrophotometric detection. Conjugated bilirubin was successfully determined in the concentration range from 0.05 microgram/ml to 5 micrograms/ml with a 96-well microplate reader absorption spectrophotometer.     

OGG1 protein suppresses G:C-->T:A mutation in a shuttle vector containing 8-hydroxyguanine in human cells

8-Hydroxyguanine (8-OHG) is an oxidatively damaged mutagenic base which causes G:C-->T:A transversions in DNA. OGG1 was cloned as a human gene encoding a DNA glycosylase that specifically excises 8-OHG from DNA in vitro. However, it was not clear whether OGG1 protein suppresses G:C-->T:A transversions caused by 8-OHG in human cells in vivo. In the present study we have examined the ability of OGG1 protein to suppress G:C-->T:A transversions caused by 8-OHG in human cells by bacterial suppressor tRNA (supF) forward mutation assay using a shuttle vector DNA, pMY189. Introduction of a single 8-OHG residue at position 159 of the supF gene in plasmid pMY189 resulted in a 130-fold increase in mutation frequency compared with untreated plasmid pMY189 after replication in the NCI-H1299 human lung cancer cell line. G:C-->T:A transversions at position 159 were detected in >90% of the supF mutants from the 8-OHG-containing plasmid. The mutation frequency of the 8-OHG-containing plasmid was significantly reduced by overexpression of OGG1 protein in NCI-H1299 cells and, in particular, the occurrence of G:C-->T:A transversion at position 159 in the supF gene was suppressed. Furthermore, frequencies and spectra of mutations of the untreated pMY189 plasmid did not differ significantly with overexpression of OGG1 protein. These results indicate that OGG1 protein has the ability to suppress G:C-->T:A transversions caused by 8-OHG in human cells in vivo.     

Biochemical evidence for localization of AMPA-type glutamate receptor subunits in the dendritic raft

A low density Triton-insoluble fraction with characteristic lipid composition was prepared from synaptic plasma membrane from the rat forebrain. The fraction was named dendritic raft based on its absence of the presynaptic marker synaptophysin, the presence of postsynaptic Glutamate receptor (GluR) subunits, and its resemblance to raft, caveolae-like structure. We found a differential distribution of NMDA-type and AMPA-type GluR subunits in the dendritic raft and postsynaptic density (PSD) fractions; the latter type GluR subunits were localized to the dendritic raft as well as PSD fraction, whereas the former type was mostly localized to the PSD fraction. We also found the differential distribution of the components of ras/mitogen-activated protein kinase (MAPK) pathway to the dendritic raft and PSD fractions. Dendritic raft and PSD may possibly interact at the postsynaptic sites for efficient signal processing that is required for expression of synaptic plasticity.     

Postoperative Fecoflowmetric Analysis in Patients with Anorectal Malformation

Because conventional methods of evaluating anorectal function do not necessarily provide good correlations between investigative results and symptoms in patients who have undergone surgery for an anorectal malformation (ARM), we recently introduced feco-flowmetry (FFM) to simulate natural anorectal evacuation. The purpose of this study was to embody significant parameters to elucidate the dynamics of anorectal activity on FFM. The parameters of FFM were compared with those of manometry and Kelly's clinical score (KCS) in 24 patients who underwent surgery for an ARM. There were three fecoflow patterns, namely, block (B) type, segmental (S) type, and flat (F) type. The B-type or S-type patterns were seen in patients classified as "clinically good." There were close relationships between the fecoflow pattern and both the operative procedure and the KCS (P = 0.01 and 0.001, respectively). Maximum fecal stream flow rate (Fmax) precisely reflected the tolerance rate of intended normal saline solution in the colorectum (TR), the evacuative rate (ER), and KCS. Fmax > 45 ml/s or TR > 70% or ER > 50% was statistically regarded as the borderline of fecal continence. Thus, the fecoflow pattern might reflect the motor activity of the pelvic floor muscle. FFM provided quantiative and qualitative evaluations concerning anorectal motor activity in patients who had undergone surgery for an ARM.     

High-Output Heart Failure Caused by a Huge Renal Arteriovenous Fistula After Nephrectomy: Report of a Case

Postnephrectomy renal arteriovenous fistula (AVF) with an aneurysmal lesion is a rare clinical entity that may cause high-output heart failure. In this report, we describe the case of a 68-year-old man who had undergone nephrectomy for renal tuberculosis 43 years previously, in whom an acquired large renal AVF presenting as an aneurysm caused congestive cardiac failure. We also discuss the hemodynamic, hormonogenic (human arterial natriuretic polypeptide; hANP), and radiographic findings before and after surgery for the AVF. The AVF with an aneurysmal lesion was clearly visualized by three-dimensional-computerized tomographic (CT) scanning, and proximal ligation of the renal artery was followed by an uneventful recovery. This procedure can produce good results when a fistula is too large to allow safe embolization and when excision would be hazardous due to inflammation surrounding the fistula. Received: March 1, 2000 / Accepted: November 20, 2000