Relationship of in vivo antitumor activities of fluorinated pyrimidines to thymidylate synthase activity and intratumoral concentrations of 5-fluorouracil and uracil

MOPC-104E plasmacytomas were subcutaneously transplanted into BALB/c mice and after 7 days the mice were administered different fluorinated pyrimidines at 4 times the clinical doses, 5-fluorouracil (5-FU, 15 mg/kg), tegafur (FT, 100 mg/kg) or UFT (FT, 20 mg/kg + uracil, 44.8 mg/kg) daily for 7 days. Tumor growth was most effectively inhibited in the UFT group. The % inhibition of tumor growth on day 14, while not correlating with the concentration of 5-FU in the tumor, negatively correlated with the concentration of uracil, which was lowest in the UFT group. The activity of thymidylate synthase (TS) was measured using a 5-fluoro-deoxyuridine monophosphate (FdUMP) binding assay. The total and free TS activities in the tumor negatively correlated with the % inhibition of tumor growth, and were lowest in the UFT group. However, the % inhibition of TS activity in the tumor, which was about 80% in all 3 groups, did not correlate with the tumor-inhibitory effect. These results suggest that uracil in the tumor may play an important role in the metabolism of fluorinated pyrimidines, and that exogeneously administered uracil may decrease the amounts of uracil and TS in the tumor, and subsequently cause 5-FU accumulation.     

Osteosynthesis for old, established non-union of the lateral condyle of the humerus

In thirty elbows that had an established non-union of a fracture of the lateral humeral condyle that had occurred more than five years before, treatment consisted of one of three operations: anterior transposition of the ulnar nerve (nine patients), corrective osteotomy of the humerus and anterior transposition of the ulnar nerve (four patients), or osteosynthesis of the non-union combined with neurolysis and anterior transposition of the ulnar nerve, with or without corrective osteotomy of the humerus (seventeen patients). Of the thirty patients, fifteen had been apprehensive when using the elbow, due to lateral instability, or had had pain in the elbow. In thirteen of these fifteen patients, the non-union was treated by osteosynthesis. Afterward, the pain and apprehension disappeared, but the range of motion of the elbow decreased in all but three patients. Three patients had clicking between the humerus and radius, and the bone failed to unite in three others. Osteosynthesis is indicated for the treatment of non-union of the lateral humeral condyle only if the patient has serious pain in the elbow or apprehension when using the elbow, due to lateral instability.     

Carcinogenic effect of N-bis(2-hydroxypropyl)nitrosamine by a single administration in rats.

The carcinogenic effect of a single intraperitoneal injection of N-bis)2-hydroxypropyl)nitrosamine (BHP) was studied in male Wistar rats. Lung tumors (adenomas and adenocarcinomas) had the highest incidence (100%). Fewer neoplasms were induced in the thyroid (adenomas and adenocarcinomas, 36%), kidney (renal cell carcinomas, 8%), and the sigmoid colon (adenomas and adenocarcinomas, 9%). No pancreatic neoplasms were found.     

Analysis and occurrence of total N-nitroso compounds in the Japanese diet

A quantitative technique for differentiating the total N-nitrosamides from the total N-nitroso compounds has been devised. The principle of this method is based on the chemiluminescence response of a nitroso compound under different denitrosating conditions. We also examined the effect of nitrite scavengers on the stability of N-nitroso compounds and found that both ammonium sulfamate and hydrazine sulfate can be satisfactorily used for the detection of chemiluminescence response with hydrogen bromide-acetic acid reagent. A survey of the occurrence of total N-nitroso compounds, total N-nitrosamides, volatile N-nitrosamines, nitrates and nitrites in the Japanese diet has been conducted. Fairly high levels of total N-nitroso compounds were detected in salt-fermented vegetables, the highest being 2 500 micrograms/kg in hakusai-zuke (salt-fermented Chinese cabbage), followed by 253 micrograms/kg in takuan (salt-fermented radish roots). It is noteworthy that the amounts of total N-nitroso compounds in these products almost coincided with those of total N-nitrosamides, although no appreciable amounts, or only trace quantities, of volatile nitrosamines could be detected in these vegetable products.     

Effects of uroguanylin, an intestinal natriuretic peptide, on tubuloglomerular feedback.

Uroguanylin is an endogenous peptide that stimulates cyclic guanosine monophosphate (cGMP) production via the activation of guanylate cyclase C (GC-C) in the intestine and kidney. A high salt diet, but not intravenous salt load, enhances the secretion of biologically active uroguanylin from the intestine and increases its concentration in plasma and urine. Our purpose is to clarify the effect of uroguanylin on renal microcirculation and the tubuloglomerular feedback (TGF) mechanism. Clearance and micropuncture experiments were performed in anesthetized rats. TGF responsiveness was assessed in superficial nephrons by measuring the changes of early proximal flow rate (EPFR) in response to orthograde loop perfusion at 40 nl/min with artificial tubular fluid (ATF). Reductions in EPFR induced by loop perfusion during intravenous infusion of uroguanylin at the rate of 10 and 50 nmol/kg/h were similar yet significantly less than that during the control period (33+/-3% and 35+/-3% vs. 47+/-3%, p<0.05). Intraluminal application of uroguanylin at 10(-7) and 10(-5) mol/l in ATF decreased EPFR by 40+/-3% and 33+/-7%, respectively, with the latter value being significantly less than the control (p<0.05). Intravenous infusion of uroguanylin did not significantly change whole kidney function. Administration of atrial natriuretic peptide (ANP), which activates GC-A and B, significantly suppressed TGF-mediated EPFR reduction either intravenously (10 nmol/kg/h) or intraluminally (10(-5) mol/l in ATF) (9+/-3% and 13+/-2% vs. 47+/-3% of the control, p<0.05). In conclusion, uroguanylin clearly suppresses TGF both through intravenous and intraluminal routes, although the effects on glomerular microcirculation and whole kidney function are far less than those of ANP.     

Removal of airborne bacteria by filtration using a composite microporous membrane made of a pyridinium-type polymer showing strong affinity with microbial cells.

A composite microporous membrane made of poly(N-benzyl-4-vinylpyridinium chloride) that showed strong affinity with bacterial cells was prepared as a filter material for removing airborne bacteria. Thickness, pore diameter and porosity of the membrane were 0.72 mm, 14.5 microm and 63%, respectively. Electron micrographic analysis revealed that the membrane consisted of a very large number of connected beads of 1.4 microm in diameter made of the pyridinium-type polymer. Filtration using the membrane was performed easily at low flow rates with insignificant pressure drop across the membrane. Filtration at 63.7 cm/sec gave 99.98% and 99.996% removal (3.7 and 4.4 log10-unit reduction in concentration) of Escherichia coli and Pseudomonas aeruginosa, respectively. Staphylococcus aureus was not detected in filtrates. Since pores of the membrane were much larger than these bacteria, the efficient removal was best explained in terms of the affinity of the polymer with bacterial cells.     

Anaplastic Giant Cell Tumor With Mucinous Cystadenocarcinoma of The Ovary Origin of the Giant Cells

The present case is that of a 27 years old woman who had received right oophorectomy for ovarian cancer nine years previously. The histological diagnosis at that time was mucinous cystadenocarcinoma with anaplastic areas. The patient expired ten years after oophorectomy due to widespread metastases of the tumor. Review of the histological slides revealed ovarian giant cell tumor which was considered to be of epithelial origin differing from those appearing in giant cell tumor of bone.