[A case of ischemic lesion in the large intestine associated with Buerger's disease].
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Biomedical subjects
Publications and source records attributed to K Okajima.
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The relationship between nuclear DNA content measured by cytofluorometry and the prognostic factors, especially the histological lymph node metastasis was investigated in patients with breast cancer. Nuclear DNA content was measured in 82 cases to evaluate its clinical significance concerning the malignancy grading. Histograms of DNA content were classified into two basic ploidy patterns based on presence or absence of a prominent peak at the 2c (diploid) region. D type (diploid type) which had a prominent peak at the 2c region resembled the histogram pattern of normal cells more closely than N type (non-diploid type). The rate of lymph node metastasis of N type (57.4%) was significantly higher than that of D type (28.6%) (p less than 0.05). The rate of lymph node metastasis of N type was higher than D type regardless of the tumor size or histological types. The five year cumulative survival rate of D type (91.7%) was significantly higher than that of N type (68.2%) (p less than 0.05). Despite the lymph node metastasis, the survival rate of D type was higher than that of N type. From a view point of the relationship between nuclear DNA content and lymph node metastasis, breast cancers of D type might be much safer indications for modified radical mastectomy. From this study, it was suggested that the measurement of nuclear DNA content of the breast cancer would bring the important informations about the malignancy grading and decision of the operative procedure.
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Biosynthesis of N-acetylcysteine S-conjugates of toxic electrophiles, mercapturic acids, occurs via inter-organ metabolism and transport in which liver, small intestine and kidney play an important role. Since a mercapturic acid is a hydrophobic organic anion and strongly binds to plasma albumin in vitro, the ligand-albumin interaction may affect the metabolic fate of this final metabolite in vivo. To investigate the role of the circulating albumin in detoxication and elimination of a toxic electrophile, urinary occurrence of the final metabolite was determined in normal and mutant Nagase analbuminemic rats (NAR) after administration of S-benzylcysteine, a model compound of cysteine conjugates. S-Benzylcysteine intravenously administered was excreted rapidly into urine as its N-acetyl derivative in both animal groups. However, the urinary recovery of this mercapturic acid was significantly lower in NAR than in normal animals. The lower urinary recovery in NAR was due to a rapid and random distribution of the unbound metabolite in the circulation to extrarenal tissues. In contrast, no significant difference in the urinary recovery of the final metabolite was observed between the two animal groups if S-benzylcysteine was given orally. Kinetic analysis revealed that the major part of the orally administered S-benzylcysteine was transferred to the liver and acetylated predominantly in this organ in both animal groups; the mercapturic acid which was synthesized in the liver can be transferred to the kidney and excreted into urine even in the absence of the circulating albumin. These results indicate that albumin is important for a final elimination of a mercapturic acid when animals were extraorally challenged with a large dose of toxic electrophiles by which the rate of biosynthesis and the plasma level of the amphipathic metabolites were increased.
To elucidate the mechanism of resistance of hypoalbuminemic patients to furosemide, the effect of this diuretic on urine volume of normal and analbuminemic rats (NAR) and of hypoalbuminemic patients was studied. Intravenous administration of furosemide rapidly enhanced sodium diuresis in normal rats but not in NAR. Total plasma clearance and distribution volume of furosemide were much larger in NAR than in normal rats, while no significant difference in these pharmacokinetic parameters was observed for the unbound fraction of the diuretic between the two animal groups. In contrast, urinary secretion of furosemide was significantly lower in NAR than in normal rats. Injected furosemide bound to albumin markedly promoted diuresis in NAR, while the same dose of albumin alone had no effect, indicating that binding to albumin is essential for the delivery of furosemide to the kidney, the site for its action. Injection of the complex rapidly increased the urine volume of hypoalbuminemic patients who showed a marked resistance to this diuretic. Thus, the resistance to furosemide in both NAR and hypoalbuminemic patients may be explained on the same basis.
The bioavailability of a film-coated tablet of valproate (VPA) in nonfasting volunteers was studied. Ten healthy adults received a single 200 mg (mean 3.55 mg/kg) film-coated tablet, 15 minutes after breakfast. Venous blood was then taken at regular intervals of up to 4 or 7 hours after the dosage, and the serum VPA concentrations were determined by means of a fluorescence polarization immunoassay. VPA was slowly absorbed with the peak concentrations occurring 1.5 to 4 hours after the administration. The mean concentration (Cmax) and extent of absorption (area under the concentration-time curve) between 1 and 4 hours were 22.2 micrograms/ml and 59.3 micrograms.h/ml, respectively. It was concluded that Cmax with a film-coated tablet of VPA can be detected if blood is taken at around 3 hours after the dosage under nonfasting conditions.
A 2 month-old Japanese girl with hereditary orotic aciduria type I was treated with oral uridine supplement. The activities of orotate phosphoribosyltransferase (OPRT) and orotidine-5'-phosphate decarboxylase (ODC) in erythrocytes were 2.7 and 0.4%, respectively, of those in the controls. Megaloblastic anemia, excessive urinary excretion of orotic acid, lymphopenia and decreased number of OKT3 positive lymphocytes on admission were corrected after the uridine supplement. Peripheral blood lymphocytes (PBL) were cultured for 24 hr in RPMI 1640 medium with 10% heat-inactivated fetal calf serum and further stimulated with PHA-P, ConA or PWM in the presence of 10 to 1000 microM uridine. EB virus-transformed B cell line (LCL) maintained with an optimal concentration of uridine was cultured for 48 hr in uridine free medium and cultured for an additional 48 hr with 1 to 1000 microM uridine. The incorporations of leucine in to PHA-, ConA- and PWM-stimulated PBL and into LCL of the patient increased in the presence of uridine over 10 microM, although they did not increase in controls. These data suggest that low protein synthesis might correlate with an immune deficiency in hereditary orotic aciduria type I.
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Gastric cancers that have invaded in the duodenum were clinicopathologically studied in 83 patients in an attempt to clarify surgical therapeutic problems. The classification and results are itemized below. 1) The extensive forms of these cancers were found to include the types of continual superficial extension (12 patients), expansion (11), deep-layer (39), whole-layer (9), non-continual extensive intralymphatic duct type (8) and specific type (4). 2) More patients manifesting a deep-layer or intralymphatic duct cancers were Borr. 3 and 4 types with a longer distance of infiltration. All of the 14 patients with an aw (+) showed these patterns of extension. 3) The n3 (+) was more common with Nos. 12, 13 and 14 lymph nodes, and similar results were seen by RI lymphography. Thus, special care may have to be exercised in treating the duodenal stump in the gastric cancers that have invaded the pyloric ring. Pancreato-duodenectomy may be required for the removal of lymph nodes in patients with gastric cancers that show a severe infiltration into the duodenum.
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