Acta Medica Okayama volume37 issue2

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.