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A previous study has shown that a single injection of ferric nitrilotriacetate (Fe-NTA) produces hepatic parenchymal iron loading in rats. The present paper reports on iron uptake by rat liver and iron toxicity in the liver after a single injection of Fe-NTA (7.5 mg Fe/kg B.W.). Iron uptake was examined with 59Fe-NTA and Fe-[14C]-NTA. Thirty percent of the injected 59Fe was incorporated in the liver non-heme iron fraction at 3 h and retained for 240 h. Only 1% of the 14C injected as Fe-[14C]-NTA was taken up by the liver at 3 h. Gel filtration with a Sephadex G-25 column of the supernatant fraction of the liver obtained 3 h after the injection showed two peaks of 14C activity. One was eluted in the void volume, and the other corresponded to [14C]-NTA. The former had a molecular weight of 5,000-10,000 as determined with a Sephacryl S-300 column and also had 59Fe activity. The electron spin resonance spectra showed that the generation of a free radical in the liver was initiated within 1 h of the iron administration. The free radical generated in the serum by Fe-NTA was revealed to be superoxide by the spin trapping method. These results suggest that Fe-NTA transfers iron to transferrin in the serum and induces hepatic iron loading. Small amounts of the injected iron were taken up by the liver as Fe-NTA and generated superoxide which may have induced lipid peroxidation of the cellular membranes.

We report two cases of adult T-cell leukemia in which the disease developed in a mother, aged 62 years, and her son, aged 41 years, less than four months apart. Both mother and son showed abnormal karyotypes and high titers of adult T-cell leukemia-associated antibody.

Some cases of early gastric cancer are accompanied with complications of the upper gastro-intestinal tract. The characteristics of these complications were investigated, and the problems of diagnosis and treatment were discussed. Out of 297 cases of early gastric cancer, 18 cases were accompanied with complications of the upper gastro-intestinal tract, including 11 cases of bleeding, a case of perforation and 6 cases of pyloric stenosis. All 18 cases were of the macroscopically depressed type, and about 85 percent of the 297 early gastric cancer cases were of the depressed type. The depressed lesions were often accompanied by ulceration which was an important factor causing the complications, and the mechanism of which appeared to be the same as that of a benign ulcer. There are some cases of early gastric cancer which are discovered by their complications, and it would be more difficult to find an early gastric cancer lesion if there were a benign lesion at the same time. Therefore, it is necessary to take much care when diagnosing and treating cases which have such complications. An endoscopic examination before the operation is especially important, and a biopsy is indispensable.

Stress-induced changes in the resistance due to coronary arterial stenosis of a fixed diameter and in the myocardial blood flow distal to the stenosis were investigated in the open-chest dog. Myocardial blood flow in the inner and outer third of the left ventricular wall was continuously measured with heated cross-thermocouples. The circumflex coronary artery was constricted with a thick string so that myocardial reactive hyperemia was nearly eliminated. Without constriction, a 15-second occlusion of the artery produced no significant changes in the resistance of large coronary arteries. On the contrary, in the presence of coronary constriction, a brief coronary occlusion caused a sustained decrease in distal coronary pressure and subendocardial myocardial flow during reactive hyperemia, while coronary flow returned quickly to the pre-occlusion level with significant reactive hyperemia of subepicardial flow. This change resulted in a long-lasting increase in the stenosis resistance. These results suggest that stenosis resistance changes dynamically, resulting in additional myocardial ischemia especially in the subendocardial myocardial layers.

Many aspects of the etiology and pathophysiology of reversible sudden deafness remain obscure. In order to better understand the pathophysiology of reversible sudden deafness we compared the results of two therapies which have different mechanisms of action. The results of therapy with tranexamic acid alone in 49 cases (57 ears) of sudden deafness were compared with the results of treatment with so-called antisludging agents in 65 cases (69 ears) using the chi square contingency test. The same therapeutic effect was observed in both groups despite the different modes of chemical action of the two therapeutics. A series of processes involving an increase in permeability of vascular walls and related edema, and extravascular red cell oozing due to hypoxia or anoxia leading to tissue damage in the inner ear seem to be important factors in the etiology and pathophysiology of reversible sudden deafness.

Descemet's membrane was isolated from the corneas of cows and observed by electron microscopy after negative staining with 1% phosphotungstic acid solution, pH 7.2. Ultrastructurally, bovine Descement's membrane had a very regular hexagonal pattern. Nodes were connected to the six others around each of them by thin filaments to form a hexagon. The distance between the nodes was approximately 120 nm, the diameter of the nodes approximately 30 nm, and the width of the connecting filaments approximately 10 nm. Bovine Descement's membrane was a molecular sieve composed of nodes and filaments substantiating our molecular sieve theory of basement membranes.

We considered upper and lower airway allergies as different phases of airway allergy and MEFV patterns to vary according to the intensity of airway obstruction in maximal expiratory flow-volume and volume-time tests on fourteen patients with nasal allergy, two with allergic bronchitis, two with bronchial asthma, and sixteen nonsmoking healthy subjects. In nasal allergy, flow changes during high lung volumes were different from those in allergic bronchitis and bronchial asthma, and MEFV patterns in nasal allergy were more widely varied than those in allergic bronchitis and bronchial asthma. We classified MEFV patterns into five ones.

Metabolism of 3-mercaptopyruvate was investigated using homogenates of rat heart, liver and kidney. When 3-mercaptopyruvate was incubated with heart homogenate, L-cysteine, L-alanine, S-(2-hydroxy-2-carboxyethylthio)-L-cysteine and 3-mercaptolactate were produced. At the same time, a decrease in the amounts of L-glutamate and L-aspartate was demonstrated. These results indicate that 3-mercaptopyruvate was converted to L-cysteine by cysteine aminotransferase (EC 2.6.1.3), to 3-mercaptolactate by lactate dehydrogenase (EC 1.1.1.27), and to pyruvate by 3-mercaptopyruvate sulfurtransferase (EC 2.8.1.2), and that HCETC and L-alanine were formed from these products. In the presence of liver homogenate, 3-mercaptopyruvate was mainly metabolized by 3-mercaptopyruvate sulfurtransferase; production of L-cysteine was small and HCETC was not formed. The metabolism of 3-mercaptopyruvate in the presence of kidney homogenate was intermediate between heart and liver: a fair amount of L-cysteine was formed, but HCETC was not produced. A peak which corresponds to L-cysteine-glutathione disulfide on the chromatogram of amino acid analysis was present when 3-mercaptopyruvate was incubated with heart or liver homogenate, but not with kidney homogenate.

2-Mercaptoethanol increases the optical density of assay solutions at wavelengths between 280 to 400 nm, and therefore interferes with the measurement of protein concentration by the microbiuret method. Protein concentration can be determined in the presence of 2-mercaptoethanol up to 6 mM by modification of the method as follows: after the precipitation of protein by trichloroacetic acid in the presence of deoxycholate, the precipitate is resolubilized with NaOH solution. Dithiothreitol interfered with the protein determinations could by made in the presence of 4 mM of dithiothreitol with the modified microbiuret method. This modified method is time-saving and more reliable than other methods for protein determination, such as Lowry's method, in the presence of sulfhydryl reagents.

Blood ammonia levels in patients with various liver diseases were determined quantitatively by a simple and rapid method using the Amitest Meter System. The results were compared to those obtained by an enzymatic method and were well correlated. This simple Amitest is also useful in animal experiments, particularly when there is a need to determine blood ammonia levels serially. This paper test was evaluated as being accurate and reliable for clinical and experimental use.

Characteristics of gamma-aminobutyric acid (GABA) were investigated in the rat central nervous system by radioreceptor assay (RRA). Scatchard analysis revealed that the rat brain had two distinct GABA binding sites with an apparent dissociation constant (Kd) of 11.7 nM and 34.7 nM. The highest level of specific [3H]-GABA binding was found in the rat cerebellum. Imidazole acetic acid, a potent GABA agonist, was effective in displacing [3H]-GABA binding but beta-alanine was slightly effective in inhibiting [3H]-GABA binding. Muscimol, the most potent GABA agonist, has been used as a ligand to characterize the postsynaptic GABA receptors. However, the maximal binding capacity (Bmax) of muscimol-RRA was about 3 times larger than that of GABA-RRA, suggesting that muscimol might label not only GABA receptors but other unknown receptors as well. An endogenous inhibitor of GABA receptor binding was purified from the P2 fraction of rat brain with 0.05% Triton X-100. The endogenous inhibitor was competitive with GABA on GABA binding sites. The inhibition by the endogenous inhibitor of GABA receptor binding was blocked by the allosteric effect of diazepam. In the presence of diazepam, [3H]-GABA binding with the endogenous inhibitor was larger than that with GABA, whereas there was no difference in the absence of diazepam. This indicated that the endogenous inhibitor was not GABA itself. The molecular weight of the endogenous inhibitor was estimate by gel filtration to be less than 3,000 daltons.

Forty-one patients with small cell carcinoma of the lung were treated with a four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine. The response rate was 68% (28 responded among 41 patients), with 10 complete responses (24%) and 18 partial responses (44%). The median survival time from the initiation of chemotherapy was 11 months for patients with limited disease and 8 months for those with extensive disease. Patients who achieved complete response survived significantly longer than those who did not; the median survival time for complete responders was 14.5 months, compared to 8.5 months for partial responders and 6 months for non-responders. Myelosuppressive toxicity remained within acceptable limits, with 5% incidence of leukocytopenia (less than 1,000/microliter) and 7% incidence of thrombocytopenia (less than 50,000/microliter) following the first course of the regimen.

We applied a tumor stem cell assay using an enriched double-layered soft agar system for the detection of metastatic sites of lung cancer. Lung cancer colonies grew from 7 of 10 effusions cytologically positive for tumor cells and 7 of 10 bone marrow aspirates cytologically and histologically positive for tumor cells. Twenty-six of 29 bone marrow aspirates cytologically and histologically negative for tumor cells showed no colony growth. However, the remaining three bone marrow aspirates, which were obtained from patients with small cell lung cancer, formed colonies in soft agar. These results indicate that the tumor stem cell assay is useful for detecting metastatic sites of lung cancer.

We reported a 62-year-old man with malacoplakia of the prostate, and reviewed 49 cases of malacoplakia hitherto observed in Japan in which the lesions originated from the urogenital tract, except for one gastric case. E. Coli was emphasized as a possible causative agent for malacoplakia especially in the urogenital tract. The possible histiocytic origin of von Hansemann cells was stressed by demonstrating cytoplasmic processes and desmosomes in our prostatic case. An adjuvant use of cholinergic agents and ascorbic acid with chemotherapeutic agents was recommended for treating malacoplakia.

The complement-mediated solubilization of precipitable immune complexes (complex-release activity) in serum specimens was determined by a simplified method using peroxidase as an immune complex antigen. The results correlated well with the hemolytic activity via the classical complement pathway and that via the alternative complement pathway. This simplified method proved to be reliable and useful.

The prognoses of patients with alcoholic liver cirrhosis were compared between those who continued to drink and those who stopped. Clinical criteria were strictly set so as to control other variables affecting the prognoses. Four-year survival was significantly higher in the patients who stopped drinking than in those who continued to drink. Continued drinking worsens the prognosis of patients with alcoholic liver cirrhosis.

Glycoproteins play a significant role in neoplastic transformations. Both the levels of fucose and the activity of fucosyl transferase, which mediates the assembly of the oligosaccharide moieties of the glycoprotein chains, have been found to be elevated in neoplastic conditions. Since these elevations are common features of a variety of neoplastic cells, these two have been designated as non-specific markers of malignancy. In the present study, the fucose level and fucosyl transferase activity were determined in the sera of cancer patients and an attempt was made to establish a relationship between the two. It was found that both the fucose levels and fucosyl transferase activities showed considerable elevation in the five cancer groups studied, establishing them as useful diagnostic parameters. However, it was also observed that the rate of increased fucosyl transferase activity was not fully reflected in the resulting serum fucose levels in a few cases.

Levamisole (LMS) was given to stage III gastric cancer patients starting three days before gastrectomy, at a does of 150 mg/day for three consecutive days every other week. Survival rates of these patients were compared with those of stage III gastric cancer patients previously operated in our Department who had not received levamisole. The background factors of both groups were matched as closely as possible. Both groups were concomitantly treated with mitomycin C and FT-207. The survival rate of the LMS group was significantly higher than that of the control group when the tumor had a diameter of 4.0-8.0 cm, cancer cells infiltrated to the gastric serosa, there were metastases within the regional lymph nodes, cancer cells slightly invaded the venous capillaren and there was moderate infiltration of the stroma.

Active enhancement was induced in inbred rats with cardiac allografts using semisoluble antigens. The optimal time of antigen pretreatment and optimal dose of semisoluble antigens were examined. The presence of serum blocking factors in the sera of rats having had allografts for a long time was examined with a macrophage migration inhibition test and lymphocyte microcytotoxicity assay. Since the blocking factors of macrophage migration inhibition were increasing on the 7th day, that day was determined to be the optimal time of antigen pretreatment. The mean survival time (MST) of cardiac allografts in untreated rats was 17.2 +/- 7.5 days. Semisoluble antigens were administered at 2 mg/kg body weight 7 days before the graft, 4 mg/kg 7 days before the graft and 2 mg/kg divided over three days, 15, 8 and 1 day before the graft, and the MSTs of cardiac allografts of rats receiving these treatments were 71.2 +/- 39.9, 62.6 +/- 42.2 and 79.3 +/- 31.0 days, respectively. The MST in each group of the treated rats was significantly longer than that of the control group (p less than 0.01). Rejection of the allograft, however, was accelerated in a group treated with 8 mg/kg 7 days before the graft (MST: 8.4 +/- 3.2 days). Serum blocking factors were detected in the sera of approximately half of the rats having cardiac allografts which survived a long time.