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The effect of 6.MPR on the antibody formation of rabbits challenged with bovine serum albumin has been studied in comparison with that of 6.MP. Observation revealed that the antibody formation is profoundly suppressed when the animal is treated with 6.MPR in an appropriate dose and period in relation with the introduction of antigen. Discussion was made of the possibility of 6.MPR as a superior therapeutic agent for autoimmune diseases.

Under in vivo conditions JTC-II cells derived from Ehrlich ascites　tumor are led to destruction by lymph node cells by two processes. The　one is the interaction of lymph node cells of the C57BL (♀) mouse sensitized with Ehrlich ascites tumor cells, and the other is the interaction of　normal C57BL (♀) mouse lymph node cells treated with PHA-M. In　these two reaction systems the following differences have become clear. The regional lymph node cells from the C57BL (♀) mouse sensitized　with Ehrlich ascites tumor cells show a marked inhibitory effect on the　growth oflTC-II cells by 10 days after sensitization.　In the observations under the phase contrast microscope these lymph node cells tend to adhere around the antigenic cells by culture hour 5-6, and by culture hour 24-48 they lead the latter to undergo cytolysis. The normal lymph node cells of C57BL (♀) mouse treated with PHA show anti-growth effect oflTC-II cells. PHA-M used proves to be effective in the concentration of 2% (v/v). Likewise after such normal lymph node cells are previously treated with 2% PHA-M for 12 hours, they also inhibit the growth of lTC-II cells when two cell groups are cultured together. In such intercellular reaction between the two cell groups there is no specificity. By observations under the phase contract microscopy, by culture hour 2-3 the adherence and aggregation of lymph node cells begin to occur, and by 18-24 hours of culture the target cells are led to undergo cytolysis. In this instance, lymph node cells are prone to adhere and aggregate on one side of the target cell.

We administered a branched-chain amino acid (BCAA) infusion to 16 patients with hepatic failure and two healthy subjects, and then evaluated its effects on ammonia metabolism and amino acid metabolic pool. Immediately after the BCAA infusion, the venous blood ammonia concentration increased in 12 of 15 patients with hepatic failure and in both two healthy subjects. Glutamine (Gln) also rose in all cases following the BCAA infusion, and this rise was particularly marked in the hepatic failure group. The increase in Gln due to the BCAA infusion and the arteriovenous difference in the pre-administration ammonia concentration showed a good correlation. These results suggest an increase in glutamine cycle capacity in patients with hepatic failure.

The effects of epidermal growth factor (EGF) on neonatal intestines were examined in the rat. In 5-day-old rats, sucrase, trehalase, alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) activities in the small intestines were significantly increased after subcutaneous injection of EGF for 3 days (1 microgram/rat/day). gamma-GTP activity was also accelerated after oral EGF administration (2 micrograms/rat/day). Small intestines of 12-day-old rats injected with EGF for 10 days (1 microgram/rat/day) were significantly heavier than those of controls. These results suggest that EGF influences neonatal growth improving enlargement and functional development of their intestines.

The bony labyrinth obtained at necropsy in four cases was studied by a new computer-generated three-dimensional (3-D) system. One case was normal (control) and the other three were histopathologically confirmed cases of Mondini's dysplasia. In case 1, the cochlea had only 2 turns and the lateral semicircular canal did not make a circle but appeared as a spherical mass projecting from the utricle even though the posterior semicircular canal made a normal circle. In case 2, there were no turns in the cochlea even though the semicircular canals and the vestibule appeared normal. In case 3, the cochlea showed 1 to 1 and 1/2 turns and the semicircular canals were premature showing only bud-like projections. This 3-D imaging system, which utilizes the toggling method, provides a way of obtaining satisfactory images without markers, and the time required to obtain these 3-D images was reduced by using a video camera instead of a digitizer. One of the problems associated with the use of 3-D imaging is the long processing time. We resolved this by inputting the section images with a video camera and by picking up structures using density segmentation instead of tracing with a digitizer.

The records of 159 patients who underwent surgical resection of colorectal cancer were reviewed to assess the incidence of ovarian metastasis and to define the role of oophorectomy. Four of these patients presented with metachronous metastases, and one patient had synchronous ovarian involvement. The incidence of ovarian involvement was higher in younger patients. While most patients with ovarian involvement had the primary tumor located at the rectosigmoid region, a similar distribution of the primary tumor was observed in patients without ovarian metastasis. The histological type and degree of differentiation was similar regardless of whether or not ovarian metastasis was present. Of the patient without ovarian metastasis, 57% presented with nodal metastases and 3.2% with peritoneal dissemination, while all patients with ovarian metastasis had nodal and peritoneal involvement. Our results suggest that histological type and degree of differentiation of the primary tumor do not influence likelihood of ovarian metastasis. However, the exposure of the tumor to the serosal surface and the subsequent peritoneal dissemination may be an important route by which malignant tumor cells reach the ovaries. However, due to the wide lymphatic involvement in patients with ovarian metastasis, the lymphatic route may be important as well. Thus, we consider that oophorectomy should be performed in all postmenopausal women, when the ovaries are macroscopically affected, and in premenopausal patients with Astler-Coller B2 tumors or over.

We investigated the effects of lymphokine-activated killer (LAK) cells on epidermal hyperplasia induced by cholera toxin (CT). LAK cells showed cytotoxic activity against both tumor cell lines and proliferating normal cells including skin epidermal cells. When 1 x 10(7) LAK cells were injected intradermally together with 1.0 ng of CT, epidermal hyperplasia was markedly suppressed. The LAK effectors inhibiting epidermal hyperplasia showed surface phenotypes of asialo-GM1+, Thy-1+, Lyt-2- and L3T4-, that were different from those of LAK cells killing tumor cells in vitro. Epidermal hyperplasia induced by CT was not suppressed by topical administration of cytokines such as interleukin-2, interferon and tumor necrosis factor. Therefore, the antiproliferative effect of LAK cells might be attributed to their direct action on the epidermal cells.

Excised extensor retinacula of the first compartment and tenosynovium from 35 patients (6 men and 29 women) with de Quervain's disease were examined by light and electron microscopy to investigate the pathogenic mechanism. The patients, aged from 22-78 years, averaging 50 years, comprised the study group. Two hundred and thirty-two specimens from cadavers of 95 men and 75 women were macroscopically examined as the control. In the study group, the extensor retinaculum and tenosynovium were macroscopically thickened, and were histologically classified into 4 groups based on presence or absence of septum, and the location of retinacular thickening. Morphologically, the thickening of the tenosynovium and retinaculum was due to fibrosis in every layer, although fibroses were seen mainly in the middle layer. The ratios of proliferation of fibroblasts, myxoid changes and/or hyaline degeneration, and vascular proliferation were varied between layers. Minimal round cell infiltration was found in the retinaculum as well as in the tenosynovium. The results also indicate that the Iwahara-Nozue test can be used to accurately predict relatively greater thickening of the retinaculum on the extensor pollicis brevis side. Based on clinicopathological analyses, it appears that de Quervain's disease is induced not only by extrinsic factors such as superficial friction but also by intrinsic factors.

The effects of the combination of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha) on the induction of apoptosis were investigated by immunohistochemical analysis with BM-1/JIMRO monoclonal antibody in RPMI 4788 tumor cells. Few tumor cells in the control culture could spontaneously undergo apoptosis. The number of positive cells increased at 2 and 4 h after treatment with nHuTNF-alpha (1 x 10(5) U/ml) and nHulFN-alpha (1 x 10(5) IU/ml). This effect was clearly maintained from 8 h up to 72 h of culture. The number of apoptotic cells also greatly increased with doses, suggesting that the apoptosis induced by nHuTNF-alpha and nHuIFN-alpha in combination was dose-dependent. nHuTNF-alpha or nHuIFN-alpha alone could induce apoptosis, but the induction increased significantly when the two cytokines were combined. These findings indicate that by combining nHuTNF-alpha and nHuIFN-alpha apoptosis can be synergistically induced in RPMI 4788 tumor cells, and may have specific therapeutic implications for clinical treatments using these two cytokines.

To study changes in hemorheologic properties during pregnancy, erythrocyte deformability was measured by an electron spin resonance (ESR) method. The results obtained by this method showed that erythrocyte deformability in normal pregnancy decreased significantly in the first trimester compared with nonpregnant controls, and continued to decrease slightly as pregnancy progressed. On the other hand, erythrocyte deformability in severe pregnancy-induced hypertension (PIH) was significantly lower than that in the third trimester of normal pregnancy. Additionally, we found that the hematocrit level needed for erythrocytes to exhibit high deformability is lower during pregnancy. These results suggest that hemodilution in normal pregnancy, so-called hydremia, compensates for the decrease in erythrocyte deformability. Conversely, since erythrocytes become less deformable in a hemoconcentration condition in severe PIH, microcirculatory disturbance of various organs, including the uteroplacental unit, may occur. The lowered erythrocyte deformability may be one of the important pathologic features in PIH.

The antidonor immune response was examined in a one haplotype-mismatched renal transplant recipient with an allograft that had been well-functioning for more than 10 years. Although the relative response of the mixed lymphocyte reaction (MLR) was (45.8)% and the MLR responder cells stimulated by donor cells produced measurable amounts of interleukin-2 (IL-2) (11.6 U/ml), the cytotoxic T lymphocytes (CTL) could not be generated against donor cells, even with exogenous IL-2. These results indicate that antidonor CTL precursors were either deleted or inactivated in this recipient.

99mTc-DTPA-galactosyl human serum albumin (Tc-GSA) is a new liver-imaging agent which binds specifically to hepatic binding protein. The purpose of this study was to evaluate the usefulness of Tc-GSA in quantitatively evaluating hepatic ischemia-reperfusion injury in the rat. Regional hepatic ischemia was induced by clamping the left hepatic artery and the left portal vein for 5 to 45 min. A hepatic accumulation index (t90) was obtained on the basis of the dynamic data. A significant difference of this index was observed between all ischemic groups and the control. In conclusion, 99mTc-GSA appears useful for evaluating the hepatic ischemia-reperfusion injury.</P>

Iliac arteries were occluded in adult mongrel dogs to investigate pelvic hemodynamics. When the unilateral common iliac artery was occluded, the blood flow making a "stopover" within the pelvis was found to be significantly less than that of anatomical hemodynamics even under a resting condition. The blood flow decreased more significantly under exercise loading than under a resting condition, which demonstrates the presence of the "steal" phenomenon. This only occurs in the collateral circulation in the pelvis formed by two arterial systems which are related in a series. In deciding the appropriacy of reconstruction for the internal iliac artery in patients with aorto-iliac occlusive disease, this "steal" phenomenon should be kept in mind. In most cases, ischemic symptoms in pelvic organs may be due to a simple decrease of the blood flow supplied to the pelvis, or due to the "steal" phenomenon. If the pelvic region is in the state of ischemia owing to the "steal" phenomenon, reconstruction of the blood vessels flowing into the pelvis is not required.

A 40-year-old man with valvular heart disease was successfully treated using a left ventricular assist device (LVAD) after open heart surgery. Echocardiography revealed left ventricular ejection fraction (LV-EF) at LVAD on/off: 23.4%/14.6% on the 4th, 23.8%/23.8% on the 5th, and 23.8%/26.8% on the 6th postoperative day (POD), respectively. The patient was weaned from LVAD on the 8th POD and discharged from the hospital on the 58th POD. The LV-EF improved to 54% 6 months after surgery and increased from 57% to 64% in response to exercise stress testing 1 year after surgery.

Membrane fluidity in human erythrocytes was measured by a spin label method using an electron spin resonance spectrometer in healthy volunteers after ingestion of alcohol (1.5 ml of whisky/kg body weight). Fluidity in the lipid bilayer closer to the hydrophilic face decreased at 30 min and 90 min, and fluidity in the hydrophobic core decreased at 90 min after ingestion of alcohol. In the same experiment, the level of thiobarbituric acid reactive substances in the serum decreased 30 min after ingestion of alcohol, and the triglyceride level increased and free fatty acid level decreased, and serum superoxide dismutase activity increased 150 min after ingestion. Furthermore, membrane fluidity in human erythrocytes was examined in patients with alcohol dependence syndrome who had not any alcohol for about 26 months. Erythrocyte membrane fluidity of patients with alcohol dependence syndrome was not different from that of healthy controls. However, erythrocyte membrane fluidity of the lipid bilayer closer to the hydrophilic face increased in patients who had concomitant liver cirrhosis compared with those who did not. These results suggest that alcohol affects temporal change of membrane fluidity in human erythrocytes.

To investigate the role of vitronectin in the progression of diabetic nephropathy, plasma concentrations of vitronectin were measured by enzyme-linked immunosorbent assay in patients with diabetes mellitus and compared with normal control subjects. In diabetic patients with normoalbuminuria and microalbuminuria, plasma concentrations of vitronectin were significantly higher than those of control subjects. Plasma concentrations of vitronectin in diabetic patients with chronic renal failure were significantly lower than those with normal renal function. There was a significant positive correlation between plasma concentration of vitronectin and blood platelet counts. In the early stage of diabetic nephropathy, vitronectin may be increased caused by synthesis from activated platelets. With progression of diabetic nephropathy, plasma vitronectin may be decreased because of accumulation in sclerotic glomeruli and arteriosclerotic lesions. In conclusion, the plasma concentration of vitronectin appears to be an important marker for the progression of diabetic nephropathy.

A carboxyfluorescein (CF)-enveloping soybean phosphatidylcholine liposome was used as a model of physicochemical damage of biomembranes. The liposomes were exposed to a metal-chelate complex [2 mM of ferric nitrilotriacetate (FeNTA) or cupric nitrilotriacetate (CuNTA)] plus a reductant (2 mM of ascorbate or various concentrations of reduced glutathione), and CF release from damaged liposomal membranes and the generation of thiobarbituric acid-reactive substances (TBARS) were measured. In the presence of a reducing agent, both FeNTA and CuNTA stimulated markedly CF release and an increase in the TBARS level, while in the absence of a reducing agent both of the chelate complexes showed little CF release and TBARS. The effects of H2O2 addition to the reaction system containing liposome with FeNTA or CuNTA plus ascorbate were also examined. The CF release was slightly increased by the addition of a smaller dose (0.5 mM) of H2O2 and it was inhibited by 8 mM of H2O2. A similar result was obtained in the TBARS test. These results suggest that FeNTA- or CuNTA-mediated lipid peroxidation can damage liposomal membranes physicochemically, and the redox reaction of the chelated metal itself is more important than a Fenton-type reaction in the process.

Endoscopical segmental piecemeal tumorectomy (ESPT) for nodular elevation of colorectal tumor is advantageous in terms of minimizing both surgical invasion and postoperative burden to the patients. Nodular elevation of colorectal tumors is said to occur when the body of the tumor is adenomatous and the surface of the focal cancer grows more horizontally into the lumen than vertically. We report here four cases of nodular elevation of colorectal tumors which were each treated by different surgical procedures.

An anodal direct current of 3.0 microA or 30.0 microA was unilaterally applied for 30 min or 3 h to the surface of the sensorimotor cortex of rats, and the effects of polarization on the morphology of brain cells were examined by light microscopy. After five repeated anodal polarization trials, dark neurons appeared mainly in the polarized neocortex regardless of the intensity and duration of the polarizing currents. Such dark neurons were scarce in the control animals or the animals receiving only one trial of polarization. The dark neurons were most abundant in the second to fourth layers of the ipsilateral superior-lateral convexity of the frontal cortex, but a few were present in the contralateral cortex. The dark neurons began to appear 24 h after the last polarization; thereafter almost all of these neurons gradually reverted to their normal morphological profiles through a transitory state within 1 month of the last trial of repeated polarization. No morphological changes were apparent in any of the brain structures other than the cerebral cortex. These findings indicate that repeated anodal polarization has reversible morphological effects on the cortical neurons, suggesting that the appearance of dark neurons after anodal polarization is an important index for evaluation of cortical plastic change induced by polarization.