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The effect of murine sarcoma virus of Moloney strain on central nervous system was examined morphologically in Swiss mice of different age. A single intracranial inoculation of cell-free virus solution resulted in the induction of characteristic intracerebral granulomas in 82.8% of the newborn to 5 day-old group, in 71.4% of the 6 to 10 day-old group, and in 68.0% of the 11 to 20 day-old group. The mean latency periods to tumor recognition were 16.5, 21.1, and 33.5 days, respectively. The granuloma consisted of inflammatory cell infilrations, reactive gliosis, and richly developed blood vessels. The lesions consistently contained numerous characteristic large round cells. In cases of long-survival, the findings included reparative changes, such as extensive gliosis, withdrawal of inflammation, and a decrease in the numbers of large round cells and blood vessels. These lesions were tentatively designated as "large round cell granuloma." The early foci of the granoloma were composed of proliferating glial cells and large round cells at the subependymal regions. Electron microscopically these large round cells had abundant intracytoplasmic fibrils quite similar to gliofibrils. Numerous C-type virus particles were present in the intercellular nad perivascular spaces, and occasionally budded from cell membranes of the large round cells and vascular endothelia. The large round cells were considered to be reactive astrocytes activated by biral infection. It was conclided that MSV-M was not a sarcomogenic but a granulomogenic virus in mice. Control animals showed no pathological changes.

The plasma fatty acid composition of cirrhotic patients and their dietary intake of fatty acids were determined. Significantly lower plasma arachidonic, docosahexaenoic, dihomo-gamma-linolenic and eicosapentaenoic acid levels were observed in cirrhotic patients than in healthy controls. A remarkably low dietary intake of polyunsaturated fatty acids supplied from fish, vegetable oil and pulses was shown in cirrhotic patients. Positive correlations were observed between plasma arachidonic acid concentrations and clearance rate of indocyanine green (KICG) (r = 0.826, p less than 0.05) and between dihomo-gamma-linolenic acid levels and cholinesterase activities (r = 0.841, p less than 0.05). From these results, we conclude that a supply of polyunsaturated fatty acids is necessary for the nutritional treatment of patients with liver cirrhosis.

Geometrical measurements of angiocardiograms of the common outflow tract (COT) of 13 patients were made to determine in which cases internal conduit repair was feasible, and under which conditions a patch enlargement of the COT was indicated. In the pulmonary stenosis (PS) group, the area of the narrowest cross-section of the COT was significantly smaller than that in the pulmonary hypertension (PH) group (p less than 0.025). In the PS group, the area was rarely sufficient to be shared by systemic and pulmonary circulation. Therefore, stenosis in the outflow tract to the pulmonary artery will occur if the intraventricular tunnel technique is applied, without patch enlargement of this portion, to patients with PS. On the contrary, the cross-sectional areas of the COT and pulmonary arteries were significantly larger in the PH group than in the PS group. Accordingly, the intracardiac conduit operation may be possible in such patients without a patch enlargement, even in young patients if other intracardiac conditions allow. Preoperative angiocardiographic evaluation of the COT is helpful in preoperatively selecting the proper operative procedure for this anomaly.

The isoelectric point (pI) value of 3-mercaptopyruvate sulfurtransferase (MST) from human erythrocytes was determined to be 6.3 at 10 degrees C by isoelectric focusing in horizontal slab polyacrylamide gel containing 2% carrier ampholyte (pH 3-10). The value was determined by comparison with the electrofocused bands of bovine pancreatic ribonuclease A-glutathione mixed disulfides (RNase-SG), which were composed of 8 species containing 1 (RNase-SG1) through 8 (RNase-SG8) moles of glutathione per mole of ribonuclease A with different pI values ranging from 5.3 (RNase-SG8) to 8.8 (RNase-SG1). The pI value of the same enzyme in a 110,000 X g supernatant of rat liver was 5.9, which was the same as that of rat erythrocyte enzyme. Treatments of rat hemolysate with oxidized glutathione or diamide resulted in a shift of the pI of MST to a lower value, 5.7-5.5. This shift was inhibited when these treatments were performed in the presence of dithiothreitol. These results indicate that the treatment of the enzyme with oxidized glutathione results in the formation of enzyme-glutathione mixed disulfide.

Renal tissues from 208 human necropsies were observed histologically for disseminated intravascular coagulation (DIC). The tissues were stained with hematoxylin-eosin, Mallory's phosphotungstic acid hematoxylin (PTAH) and cationic ferric hydroxide colloid stabilized with cacodylate (Fe-Cac), and tested by immunoenzyme histochemical (IEH) reaction for fibrin-related materials (FRMs). The use of the IEH method increased FRM recognition, and FRMs were detected in a total of 80 cases (38.5%). In 26 cases diagnosed clinically as DIC, FRMs were shown in 23 of the cases (88.5%). Thus, 57 patients with FRMs were clinically asymptomatic. In rats with DIC induced by endotoxin injection, glomerulus FRM was effluxed into the tubulus through the Bowman's capsule and was excreted into urine. The electric charge was reduced on the endothelial surface of the glomerular capillaries in both human and rat DIC. Under the scanning electron microscopy, the endothelial surface appeared coarse in the glomerular capillary and fibrin degradation was present. Our conclusions are: (a) PTAH is non-specific for FRMs, (b) IEH aids the pathohistological diagnosis of DIC, especially in asymptomatic forms including the compensated DIC state, (c) FRMs in tubuli suggest DIC, and (d) DIC is possibly initiated by a reduction in the capillary electric surface charge.

We investigated the antitumor effect of purified natural human tumor necrosis factor-beta (nHuTNF-beta) produced by human acute lymphoblastic leukemia BALL-1 cells stimulated with HVJ on pulmonary metastatic tumors of Lewis lung carcinoma (3LL) transplanted into BDF1 mice. nHuTNF-beta showed antiproliferative effects on metastatic tumors in a dose-dependent manner when administered daily for 10 days by the intravenous route. Histological examination of the tumors treated with nHuTNF-beta revealed that the tumor size and number of metastases were much reduced. Lytic cellular changes, including cytoplasmic vacuolation, loosening of the intercellular junction and both cytoplasmic and nuclear swelling, were found, but tumor necrosis was not. These findings indicate a therapeutic effect of Grade IIa according to the histological criteria of Shimosato and Ohboshi. In addition, synergistic augmentation of the antiproliferative effects of nHuTNF-beta by natural murine interferon-alpha/beta (nMu-IFN-alpha/beta) or recombinant murine interferon-gamma (rMuIFN-gamma) was recognized by median effect plot analysis. The results suggested that nHuTNF-beta may well deserve clinical trial as a new immunotherapeutical agent for human cancer.

The biochemical characteristics of cathepsin B secreted from cultured human liver cancer cells were examined. The enzyme activity of culture medium against a synthetic substrate, N-carbobenzoxy-L-arginyl-L-arginine-4-methyl-coumaryl-7-amide, was dependent on the addition of cysteine, and the optimal pH was found to be 6.0. No activity was observed when the enzyme source was fresh medium not used for culture. These results suggest that the enzyme released from liver cancer cells is the thiol-protease cathepsin B. The molecular weight of the enzyme with 90% of the total activity was 40,000. Two cathepsin B molecules were found in liver tissue from patients with hepatocellular carcinoma (HCC); one was equivalent in size to the secreted enzyme, and a smaller one was the same as normal liver cathepsin B (27,000), which was also obtained from HCC-bearing cirrhotic liver. These results demonstrate that two molecules of cathepsin B are synthesized in liver cancer, and that the larger one is released into the surrounding tissue.

We studied the factors which may induce acute high grade restenosis in emergency percutaneous transluminal coronary angioplasty (PTCA). PTCA was attempted in 50 patients with acute myocardial infarction, and the balloon catheter passed successfully across the occlusion site in 47 (94%) of the patients. These 47 patients were analyzed. "Acute restenosis" was defined as a lesion which was revascularized to less than 50% luminal reduction narrowed again to more than 75% luminal reduction 5 min after the balloon inflation. Univariate and multivariate analyses were used for determining factors which significantly influenced acute restenosis. The incidence of at least one restenosis episode was 45%. Multiple regression analysis selected 5 factors associated significantly with an increased rate of acute restenosis: 1) angiographic evidence of dissection, 2) lesion in the right coronary artery (RCA), 3) lack of or insufficient administration of thrombolytic agent preceding PTCA, 4) curved lesion and 5) relatively small balloon/artery diameter ratio. Acute restenosis correlated significantly with late reocclusion. This study indicates that it is important to administer a thrombolytic agent prior to emergency PTCA, and to use an adequately sized balloon to the artery when the acute restenosis occurs by using relatively smaller sized balloon. The present data also demonstrated that patients with RCA and a curved lesion have a relatively high risk of acute restenosis. This study indicates how patients with relatively high risk of acute restenosis may be identified.

Improvement in tissue perfusion following surgically induced ischemia in limbs of dogs was experimentally evaluated to clarify the improvement of hemodynamics following walking exercise in chronic, peripheral arterial occlusive diseases. With the use of a computer system in conjunction with medical mass spectrometry, the local tissue perfusion rate was calculated on the basis of the clearance curve of tissue partial pressure of CO2 following electrical stimulation of the ischemic leg to simulate exercise. Ischemia was created in the leg by ligation of the proximal and peripheral arteries. In one month, intermittent claudication improved in accordance with improvement in muscle tissue perfusion. Angiographic evidence of distal runoff became visible six months after surgery, indicating that tissue perfusion played an important role in peripheral hemodynamics. The local tissue perfusion rate improved from 9.51 +/- 2.62 ml/100 g/min to 12.41 +/- 2.42 in one month, to 14.59 +/- 3.19 in three months, to 15.11 +/- 3.24 in six months and to 17.19 +/- 2.63 in twelve months. The improvement of ischemic symptoms following long-term exercise is attributed to improvements in tissue perfusion or collateral circulation.

One hundred patients who underwent heart valve replacement during the years 1977 to 1985 were reviewed an average of 57 months after surgery. The overall rate of reemployment after the operation was 78%. The most important factors influencing the return to work were the employment status before surgery, age at the time of surgery, the number and site of the diseased valve, the preoperative New York Heart Association (NYHA) functional class and the number of times cardiac surgery was performed. These factors were closely related to the optimal timing of heart valve replacement. It was suggested that the rate of return to work and the quality of life would be improved if the heart valve replacement had been performed at an earlier stage of the disease.

Preparations of IgG2b purified from several mouse hybridoma clones were highly susceptible, compared to other subclasses, to peptic digestion under conditions usually used to prepare F (ab')2 fragments. Analyses of the digestion products revealed that no F (ab')2 was produced and that the main product was a Fab-like fragment. Demonstration of the hinge disulfides in the Fc portion clearly indicated that in IgG2b the primary peptic cleavage occurs on the NH2-terminal side of the inter-heavy chain disulfide bridge. The resulting Fab failed to bind with antigen, suggesting the importance of the CH1-hinge region in maintaining the native conformation of the antigen-binding site.

Ether and restraint stress-induced peripheral plasma corticotropin releasing hormone (CRH), arginine vasopressin (AVP), oxytocin (OXY) and adrenocorticotropin (ACTH) levels were measured by radioimmunoassays. Plasma CRH, AVP, OXY and ACTH rose to approximately twice the level of control rats 2 min after the onset of a 1-min exposure to ether. Plasma CRH rose further 5 min after the onset of ether stress, while plasma AVP and OXY returned to the baseline levels at 5 min. Plasma CRH, OXY and ACTH showed significant elevation 2 min after the onset of restraint stress, while plasma AVP did not show a significant change. Plasma OXY and ACTH rose further 5 min after the onset of restraint stress, whereas plasma CRH returned to baseline levels. CRH and OXY concentrations in the hypothalamic median eminence decreased 5 min after the onset of ether exposure and restraint, while the AVP concentration did not differ from control levels. The results, including the discrepancy between plasma CRH and ACTH 5 min after stress, suggest that CRH in the peripheral plasma is derived from both hypothalamic and extrahypothalamic tissues. The levels of stress-induced CRH in the peripheral plasma were sufficient to stimulate ACTH release. These results suggest that ether and restraint stress elevate plasma CRH shortly after the onset of the stress, and that this elevation in the plasma CRH level is at least partly responsible for stress-induced ACTH secretion.

In an acute study, cholecystokinin octapeptide sulfate (CCK) in doses of 1, 10 or 100 micrograms/kg body weight was injected intraperitoneally into rats just prior to the dark cycle. Rats were sacrificed two hours following the CCK injection. Norepinephrine levels were elevated in the dorsal amygdala of rats injected with 10 micrograms of CCK as well as in the septum of rats injected with 1 and 10 micrograms of CCK. The dopamine level in the septum of rats injected with 1 microgram of CCK as well as the gamma-aminobutyric acid (GABA) level in the lateral hypothalamus of rats injected with 10 micrograms of CCK were also elevated. In a chronic study, CCK (1 microgram/kg body weight/h) was subcutaneously infused into rats with Alzet osmotic minipump for seven consecutive days. The daily food consumption did not change during the 7 days of CCK infusion. The dopamine turnover in the striatum accelerated and the GABA level increased. On the contrary, dopamine metabolism in the substantia nigra and locus coeruleus decreased. Furthermore, the serotonin level in the substantia nigra decreased. Norepinephrine levels decreased in the nucleus paraventricularis, the locus coeruleus and the substantia nigra. The results suggest that peripherally administered CCK may act on the monoaminergic neurons and GABAergic neurons in the brain.

Co-cultivation of thymus and spleen cells of Fisher and Lewis rats with lethally irradiated MT-2 cells harboring human T-cell leukemia virus type I (HTLV-I) resulted in the establishment of lymphoid cell lines, FIRT-1, FIRS-1, LERT-1, and LERS-1, respectively. Cells of these cell lines had rat T-cell characters as demonstrated by the positive reaction to monoclonal antibodies (MAbs) to rat T cell antigens (Thy 1 and pan T). They lacked surface immunoglobulins and strongly expressed rat interleukin-2 receptor antigen (Tac) and Ia antigen. Karyotypic analysis revealed that they had the normal rat karyotype in early cultures, but showed marked aneuploidy after long cultivation. None of them expressed HTLV gag proteins (p19 and p24) or virus particles, but they contained HTLV-I proviral DNA monoclonally and weakly expressed pX gene products (p40x). They were not transplantable into syngeneic newborn rats.

Anti-Epstein-Barr virus (EBV) antibodies were tested in 11 children with chronic active EBV infection. Anti-virus capsid antigen (VCA)-IgG antibody titers ranged from 1:640 to 1:10,240. Anti-VCA-IgM antibody was consistently positive in 5 of the 11 patients; anti-VCA-IgA antibody was consistently positive in 6 of the 10 patients; anti-early antigen (EA)-IgG antibody was consistently positive in 10 of the 11 patients and anti-EA-IgA antibody was consistently positive in 4 out of the 7 patients. Anti-EBV nuclear antigen (EBNA) antibody was not detected in two patients. Consistently positive anti-VCA-IgA- and anti-EA-IgA- antibody may be a characteristic feature of abnormal antibody responses in severe chronic active EBV-infection in childhood.

Seventeen patients having extracardiac valved conduits placed between the right ventricle and pulmonary artery were followed for 7 to 87 months postoperatively (mean, 42 months), at the Heart Institute, Kenritsu Amagasaki Hospital, Japan. There were no late deaths in the study group. Three conduits have been replaced, all because of conduit stenosis. In two-dimensional echocardiographic examinations, commissural fusion and calcification of the valve were noted in 6 out of 16 xenograft valved conduits. Mechanical valve immobility was found in one patient. Neointimal peel of the dacron graft was noted in 6 out of 17 cases, and marked left ventricular deformity in the short axis view was found in 6. Late cardiac catheterization was done in 6 patients who were suspected of having valve failure and right ventricular hypertension by two-dimensional echocardiography. All 6 of these patients showed a high pressure gradient between the pulmonary artery and right ventricle and also had elevated right ventricular pressure. In conclusion, two-dimensional echocardiography is a simple, non-invasive and very accurate method for detecting conduit stenosis and valve failure. An echocardiographic series should be performed for a long-time postoperatively because obstructions of valved conduits may be progressive, and an operation may be advisable in order to prevent the development of advanced right ventricular hypertrophy and deterioration.

In order to improve the postoperative prognosis of gastric cancer patients we have performed preoperative endoscopic intratumoral administration of various biological response modifiers. In the present study we have investigated the kinetics and the immune response augmenting effect of intratumorally injected PSK, a protein-bound polysaccharide preparation, by immunohistochemical methods using anti-PSK antibody and various other antibodies. PSK-containing cells were located in the tumor tissues and follicular marginal zones of regional lymph nodes. Intratumorally administered PSK appeared to be phagocytized by the histiocytes and to cause them to become antigen-presenting cells. These cells may play a major role in augmenting immune responses in gastric cancer patients.

We report a case of unilateral hyperplasia of the adrenal medulla. The patient showed clinical features suggestive of pheochromocytoma. Removal of the hyperplastic adrenal gland resulted in complete disappearance of all prior symptoms, decrease of the plasma and urinary catecolamine levels and no high uptake in [133I] metaiodobenzylguanidine scintigraphy. A histological study revealed diffuse hyperplasia of the adrenal medulla. Up to now, there are relatively few reports of adrenal medullary hyperplasia in English literatures.

A new volatile derivative of taurine, N-isobutoxycarbonyltaurine methyl ester (methyl 2-(N-isobutoxycarbonylamino)ethanesulfonate), was prepared by a three-step procedure for the gas chromatographic determination of taurine in urine. First, taurine was converted to its silver salt by reaction with silver oxide; next the silver salt was reacted with isobutyl chloroformate to form the N-isobutoxycarbonyl derivative, and finally the derivative was reacted with methyl iodide to form N-isobutoxycarbonyltaurine methyl ester. The volatile derivative was analyzed by gas chromatography using a column of 3% OV-101 on Chromosorb W. When methyl 3-(N-isobutoxycarbonylamino) propanesulfonate was used as an internal standard, the calibration curve was linear between 0.5 and 5.0 mumol of taurine/ml and showed a good reproducibility. This method was applied to the determination of taurine in human urine. Recovery was 98.6 +/- 5.2%, when 1.25 to 5.0 mumol/ml of taurine was added to human urine.