The determination of thymidylate synthetase inhibition for testing fluoropyrimidines--pharmacokinetics and metabolism of carmofur (HCFU) in patients with gynecologic malignancies--Tokai HCFU Study Group for Gynecologic Malignancies

The pharmacokinetics and metabolism of carmofur (HCFU) were studied. Sixty-six patients were administered 100 mg of HCFU orally, and the plasma levels of the HCFU fraction (HCFUf) and 5-fluorouracil (5-FUra) were determined at 0, 1, 2, 4 and 6 hours. The average half-life of HCFUf and 5-FUra were 1.05 and 1.31 hours, and the average areas under the curves (AUC) of the plasma concentration were 6.51 hr X mcg/ml and 0.46 hr X mcg/ml, respectively. Surgical specimens of the tumors were obtained about three hours after the administration and assayed for HCFUf. 5-FUra fluorodeoxyuridine-monophosphate (FdUMP), deoxyuridine-monophosphate (dUMP), total thymidylate synthetase (TS total), and non-FdUMP-bound free enzyme (TS free). The TS inhibition rate (IR) was calculated by the follow method: IR = (TS total-TS free)/TS total X 100 levels of the TS total varied from not-detected (less than 0.10 pmol/g) to 20.5 pmol/g. The average FdUMP: dUMP ratio was 3.44 X 10(3), However, more than 80% inhibitions of TS were observed in nine cases (21.4%). The correlation indicates between TS IR and tissue FdUMP level or FdUMP: dUMP ratio were 0.57 and 0.62 in ovarian malignancies respectively. No significant correlations were observed between TS inhibition and levels of tissue 5-FUra or AUC of 5-FUra.     

Changes in somatosensory evoked responses by repetition of the median nerve stimulation

OBJECTIVE: We investigate the synaptic factor for the recovery function of evoked responses using a repetitive stimulation technique. METHODS: Somatosensory evoked cortical magnetic field (SEF) was recorded following stimulation of the median nerve using single to 6-train stimulation in 8 healthy subjects. The SEF responses after each stimulus in the train stimulation were extracted by subtraction of the waveforms. RESULTS: An attenuation of the SEF components was recognized after the second of the stimuli, but there was no significant attenuation with the third or later stimulations. The root mean square (RMS) of the 1M (peak latency at 20 ms after stimulation) and 4M (70 ms) components were smaller than that of the single stimulation during the train stimulation, while the 2M (30 ms) and 3M (45 ms) components were not attenuated, but the 3M was facilitated at the fourth to sixth stimulation. CONCLUSION: The synaptic factor was not responsible for the attenuation of the SEF components during repetitive stimulation in healthy subjects. The SEF change disclosed a functional difference among the SEF components during the train stimulation, especially among the later components.     

Removal of micro-organisms by filtration through unwoven cloth coated with a pyridinium-type polymer.

Unwoven cloth coated with 32 mg/g of a copolymer of N-benzyl-4-vinyl-pyridinium chloride and styrene was found to be effective in removing micro-organisms from water. In experiments demonstrating removal of Escherichia coli by filtration through ten sheets of the unwoven cloth, the rate of removal was 99.99% at a filtration rate of 2.6 cm/h, and remained at 99% even at a high filtration rate of 300 cm/h and a low influent concentration of the bacterial cells such as 10(3) cells/ml. The rate of removal tended to increase with a decrease in the influent bacterial concentration. Seven other bacteria and two yeasts were effectively removed by filtration through the unwoven cloth. Filtration through the unwoven cloth was also effective in removing spores of fungi from water but was not very effective in removing bacteriophage T4 from aqueous solution.     

Application of in vivo microdialysis to pineal research in birds: Measurement of circadian rhythms of melatonin

Circadian rhythms of pineal melatonin release were measured in free-moving pigeons, Japanese quails, and chickens under light-dark cycles followed by constant dim light. Although melatonin levels differed among individual birds, circadian rhythms of melatonin were observed in all of them. Using this technique, we could examine phase shifts of melatonin rhythms and suppression of melatonin release by photic stimulation in pigeons. We could also examine effects of norepinephrine infusion on melatonin release. These results indicate that microdialysis is useful for the study of pineal melatonin rhythms in birds.     

Ca antagonist ameliorates glomerular injury via suppression of glomerular hypertrophy in spontaneously hypertensive rats

Summary: A study was conducted to determine whether calcium blockers (CCB) have renoprotective effects, and if so to elucidate the mechanisms of such effects.
A total of 30 uninephrectomized (UNX) spontaneously hypertensive rats (SHR), 5 weeks of age, were divided into three groups. Group 1 was fed a diet containing 0.01% manidipine and 8% NaCl, while groups 2 and 3 were fed diets containing only 8 and 0.5% NaCl, respectively. Feeding of these diets began 7 days after UNX (experimental day 0). Bodyweight, urinary protein /24 h, urinary sodium excretion/24 h, and food intake were measured at certain time intervals.
At time of death (day 9 or 21), estimations of inulin clearance (Cin) and morphological evaluations, determination of glomerular sclerosis index (GSI), tubulointerstitial index (TII) and glomerular volume were performed.
Urinary protein was significantly higher in groups 1 and 2 than in group 3 from day 7 onward, but did not differ between the former two groups. Cin in group 2 was higher than in groups 1 and 3 on day 9, but declined to lower levels than in groups 1 and 3 by day 21. There was no difference in Cin between group 1 and group 3 on day 21. Morphometry (GSI and TII) revealed that renal lesions were more progressive in group 2 than in group 1. Glomeruli in group 2 were markedly larger than those in group 1, but no difference in glomerular volume was noted between groups 1 and 3.
Our findings suggest that CCB prevent progression of renal injury induced by accelerated hypertension in UNX SHR. the mechanisms of prevention may, at least in part, be related to suppression of glomerular hypertrophy. Inhibition of renal injury can be achieved without significant reduction of proteinuria.     

Major histocompatibility complex class II antigens on renal cell cancer--immunohistochemical study and effect on their expression by interferon

Products of major histocompatibility complex (MHC) play important roles in immune reaction. Class II MHC antigens serve as restriction elements for cells presenting antigens to CD4-positive helper T cells and also as histocompatibility antigens responsible for graft rejection. Furthermore, it was reported that expression of class II antigens on tumor cells increases immunogenicity in the murine system. In an attempt to investigate the relationship between renal cell cancer (RCC) and host's immune responses, we examined the expression of class II MHC antigens on RCC tissues of 30 cases and tumor cell lines. Immunohistochemical study showed that class II antigens were detected on 29 out of 30 RCC tissues to various degrees with an order of positivity DR greater than DP greater than DQ but not normal renal tubular cells. Significant correlation was found between the expression of DQ or DP and the degree of lymphocyte infiltration. Three lines of RCC were examined by flowcytometric analysis, and were found to lack class II antigens. In KRC/Y and ACHN, however, HLA-DR-positive cells and in KRC/Y a smaller number of HLA-DP-positive cells were found when these cells were treated with interferon-gamma but not interferon-alpha. The result suggests that the expression of class II antigens on RCC might be modified by interferon-gamma which is produced by tumor infiltrating lymphocytes or administrated for cancer treatment. Their expression is considered to affect host's immune response to RCC.     

Clinical studies on the transabdominal resection of esophagocardial cancer and cervical anastomosis using bypass methods. Analysis of data on 76 patients

Transabdominal resection for esophagocardial cancer and reestablishment of alimentary continuity using bypass methods were performed in 76 patients. Thirteen underwent a bypass with a gastric tube and in 30, a colonic segment was prepared. In the remaining 33, a jejunal segment was used as a bypass organ, with considerable success. The 5 year survival rates were 68.8 per cent in those with stages (I+II), 16.5 per cent in those with stage III, 12.6 per cent in those with stage IV and 22.5 per cent in all cases, indicating similar results compared to those with cancer located in the upper third of the stomach with the limited proximal extension within the esophagocardial junction and operated on during the same period.