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Sulfated acidic mucopolysaccharides have been found to be significant components of "protein plugs" in patients with chronic pancreatitis. The precise identification of the mucopolysaccharides and their distribution within the protein plugs may clarify the pathogenesis of the plugs. Pure pancreatic juice from five patients with chronic pancreatitis was obtained by endoscopic retrograde catheterization of the papilla of Vater. Enzymes for digestion of the plugs included hyaluronidase of the bovine testes and streptomyces hyalurolyticus, chondroitinase ABC and AC, and sialidase (neuraminidase). Our study indicated that: I) Sialic acid is distributed throughout the plugs and may be a major component, followed by a lesser amount of chondroitin sulfate B. 2) Chondroitin sulfate A, C, D and E and chondroitin may be minor components. 3) Hyaluronic acid is negligible in the plugs.

The O2- production by neutrophils was examined in 4 cases of refractory anemia with excess of blasts (RAEB) in order to evaluate the possible causes of enhanced susceptibility to infection and to gain some informations on the differentiation of neutrophils in this hematological disorder. In three of the four RAEB cases there was little O2- production by neutrophils, in addition to there being morphological anomalies of the neutrophils such as a Pelger-Huet-like anomaly, granular deficiency and binucleated cells. These results suggest that the impairment of O2- production by neutrophils in RAEB is one of the possible causes of susceptibility to infection and also suggest that the differentiation of neutrophils in this hematological disorder is faulty. The estimation of O2- production by neutrophils may be a useful diagnostic method for preleukemia.

The blood levels of amino acids, ammonia and pancreatic hormones following the intragastric and intravenous administration of a branched-chain amino acid (BCAA)-enriched solution were comparatively investigated in control subjects and patients with liver cirrhosis. There was no essential difference in the time course of serum amino acid and blood ammonia levels between the intragastric and intravenous infusions. Elevation of serum insulin concentrations in cirrhotic patients was significant only immediately after the administration through the enteral route. However, plasma glucagon levels increased similarly when the BCAA-enriched solution was administered through either route. The results indicate that both enteral and intravenous infusions will have similar therapeutic effects on the impaired protein metabolism in cirrhotic patients with protein-calorie malnutrition.

Metastatic neuroblastoma cells in bone marrow aspirates were examined by the formaldehyde induced fluorescence histochemical method. With this method we could easily identify abnormal cells as metastatic neuroblastoma cells by observing catecholamine green colored fluorescence in their cytoplasma. This formaldehyde induced fluorescence histochemical method is significantly useful for the diagnosis of metastatic neuroblastoma of the bone marrow.

We studied the effect of glycyrrhizin, a compound known as an anti-inflammatory and antiallergic drug, on the membrane permeability change induced by phospholipase A2 (PLA2) and on platelet aggregation. Glycyrrhizin was found to inhibit the PLA2-induced carboxyfluorescein (CF) release from D,L-dipalmitoyl phosphatidylcholine (DPPC) liposomes. Part of this inhibitory effect of glycyrrhizin on PLA2 is accounted for by the physical state of the substrate, the DPPC liposome membrane. Glycyrrhizin also inhibited collagen-induced platelet aggregation in a concentration dependent manner, which may in part account for its inhibitory effect on PLA2.

Direct drain of the cystic duct and drain of the biliary tract through an internal fistula into the duodenum in a 81-year-old man were endoscopically diagnosed without an operation.

This report concerns an unusual case of adult T cell leukemia (ATL) complicated with progressive systemic sclerosis (PSS). The surface markers of peripheral blood mononuclear cells (PBM) and lymph node cells, both of which mainly consisted of leukemic cells, were examined. The effect of these cells on the pokeweed mitogen (PWM)-induced IgG synthesis by normal PBM also was studied. The leukemic cells formed rosettes with sheep red blood cells (SRBC; E) and expressed T cell antigen, Leu-1, and DR antigen. The detection of cell surface antigens was carried out by employing monoclonal antibodies against these antigens. We diagnosed this case as DR positive ATL. In terms of the immunoregulatory function of these leukemic cells, the co-culture experiments showed that these cells had some suppressive effect on the PWM-induced IgG production by allogeneic normal PBM.

A chronic epileptic focus was induced by a microinjection of ferric chloride solution into the sensorimotor cortex of rats. Two types of somatosensory evoked potentials (SEPs) were recorded from the cortex near the injection site. In animals showing an initial positive-negative biphasic SEP, spikes appeared in electrocorticograms (ECoGs) more frequently on the side ipsilateral to the injection site than on the contralateral side, whereas in animals showing an initial negative monophasic SEP, spikes appeared more frequently on the contralateral side.

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.