Disruption of lysosomal membranes is one of the earliest changes seen in the ischemic myocardium and a calcium-calmodulin-dependent process may be involved in irreversible myocardial injury. This study was designed to determine the effect of trifluoperazine (TFP), a calmodulin antagonist, on the isolated rat heart. To assess the cardioprotective effect of TFP, changes in the distribution of lysosomal enzymes in myocardial cells and post-ischemic myocardial recovery were studied. Experimental groups (n=6 hearts per group) were: Group I, infusion of 20°C Krebs-Henseleit bicarbonate buffer (KHB) every 30 min during ischemia; Group II, infusion of KHB containing TFP (2.5×10-6M/L); Group III, infusion of St. Thomas' Hospital cardioplegic solution (ST); Group IV, infusion of ST containing TFP (2.5×10-6M/L). Isolated perfused rat hearts were ischemic for 2 h at 20°C and were reperfused at 37°C for 30 min. Functional recovery after ischemia and reperfusion was measured by developed pressure. Addition of TFP in Group II hearts prevented leakage of lysosomal enzymes (N-acety1-β-glucosaminidase and Cathepsin D) compared with Group I (p<0.05, respectively). The activities of lysosomal enzymes in cytosol were lower in Group IV than in Group III, though the difference was not statistically significant. Hearts receiving TFP (Group II) showed improved recovery of developed pressure at 15 min and 30 min after reperfusion when compared with Group I (p<0.01, respectively). These results suggest that TFP reduces ischemia/reperfusion injury and calcium-calmodulin-dependent enzymes may play an important role in the development of cellular damage in the myocardium during hypothermic ischemia.
In order to better understand the characteristics of bronchial asthma caused by chironomid midges, cross-reactivity of midges was examined in 163 asthmatics through observation of skin reactions and specific IgE and histamine release. Positive skin reactions were observed in 17 of 73 asthmatics (23.3%) for Chironomus plumosus, 89 of 276 (32.2%) of those for Tokunagayusurika akamusi, and 33 of 128 (25.8%) of those for Chironomus yoshimatsui. Two cases of 32 (6.3%) asthmatics for Chironomus plumosus, 16 of 144 (11.1%) of those for Tokunagayusurika akamusi, and 7 of 77 (9.1%) of those for Chironomus yoshimatsui showed a significant amount of histamine release (more than 15%). Cross-reactivity was present for Chironomus plumosus, Tokunagayusurika akamusi, Chironomus yoshimatsui, by both skin tests and basophil histamine release. It is suggested that both the male and female of Chironomus plumosus have common antigenecity, and cross-reactivity was observed between them.
In order to examine the ability of complement to solubilize immune complexes (IC) in vivo, acute or chronic serum sickness nephritis was induced in 10 rabbits and 11 rats with by injection of BSA as an antigen (Ag). The animals were divided into two groups. The first received 500U or 50U/week cobra venom factor (CVF) administered intraperitoneally to reduce serum complement levels and complement-mediated solubilization of immune complexes. On the other hand, the second group received 2ml or 0.2ml/week turpentine oil (TO) injected interamuscularly to elevate serum complement levels and complement-mediated solubilization of immune complex. Renal biopsies were performed weekly with each animal, and these specimens were stained for antigen (BSA), antibody (IgG) and complement (C3) by immunofluorescence techniques. Results showed a significant difference between TO-, and CVF-treated animals with respect to the decline of IC in kidney lesions. No detectable IC (especially BSA) remained in the renal glomeruli of TO-treated nephritic animals, indicating that complement might act in vivo to solubilize IC deposited in tissues.
Immunohistochemical localization of α and β subunits of the S-100 protein in normal human brains and brain tumors was studied by the ABC method using mouse monoclonal antibodies against each subunit. In cerebral tissues, glial cells showed positive staining for both subunits, with some neurons positive only for the α subunit. In cerebellum, Purkinje cells and other neurons were negative for the α or β subunit, and Bergmann's cells were positive only for the β subunit. Low grade astrocytomas were strongly positive for the α and β subunits. In oligodendrogliomas and choroid plexus papillomas, the immunoreactivity of the β subunit was stronger than that of the α subunit. Medulloblastomas showed no positive staining for either subunit. Schwannomas were positive only for the β subunit. High grade astrocytomas, ependymomas and meningiomas manifested marked variability in the immunoreactivity for the α and β subunits of the S-100 protein. The evidence suggests that immunohistochemical examination of the α and β subunits of the S-100 protein in normal human brains and brain tumors may be useful in determining the histogenetic origin of brain tumors.
To evaluate the effects of preventive measures and medical treatment on cancer, the death rate per 100, 000 population according to Vital Statistics and the patient rate per 100, 000 population from the Patient Survey were statistically analyzed. Results revealed it to be more appropriate to use the inpatient rather than the total of both inpatient and outpatient rate, in understanding the actual condition of patients. Annual trends of patient and death rates differ among sites, sexes and age groups, suggesting that the total annual trend of all sites for cancer does not reveal the actual situation. Moreover relation between patient and death rates differed by site. It was also seen that treatment efficacy has increased for stomach cancer, but not for lung, liver (male) or breast (female) cancer.
Heterotopic homotransplantation of rat hearts was performed and ISS and NK activity levels were determined before and after rejection. The effects of prostaglandin (PGE2), cyclosporin A, and indomethacin on the acceptance of transplanted hearts as well as on ISS and NK activity were studied. PGE2 and PGI2 significantly extended survival when compared to a control group, while indomethacin decreased survival. ISS peaked 4 days before the rejection of transplanted hearts, suggesting its usefulness as a marker of rejection. Moreover, NK activity was significantly higher around the time of rejection, suggesting the importance of NK cells in this process. Finally, rejection was suppressed by administration of PGE2.
This study was carried out to assess changes in cerebrovascular tonus in acute intracranial hypertension. Incremental increases of intracranial pressure (ICP) were induced in 42 dogs by intermittent inflation of a left fronto-temporal extradural balloon until the animals showed anisocoria, whereupon the balloon was deflated. ICP was continuously monitored using a pressure indicating-balloon in the bilateral extra- or intra-dural cavities. Blood pressure was abruptly increased by administration of angiotensin II at various levels of increased ICP (IICP). The cerebrovascular tonus was calculated as the ratio of the increase in mean ICP divided by the increase in mean blood pressure and was further defined as the local vasomotor capacitance index (LVCI). CO2 reactivity of the cerebral vessels, an electroencephalogram (EEG) and the condition of the pupils were also observed. There was no significant difference between the bilateral hemispheres in local ICP (except at a balloon volume of 3 ml) and LVCI during IICP. The LVCI was 0.085±0.056 at normal ICP, and increased exponentially with increases in ICP. The maximum LVCI was 0.89. There were significant correlations between increases in the LVCI and decreases in cerebral perfusion pressure (CPP). The LVCI began to increase when CPP was below 80 mmHg, and increased markedly to more than 0.6 when CPP was below 40 mmHg. The CO2 reactivity of cerebral vessels was completely impaired when transtentorial herniation developed. After deflation of the balloon, LVCI did not recover in 7 of 14 dogs. In these animals, CPP remained below 80 mmHg, and the EEG and pupils never became normal.
We studied cardiac lymph circulation in relation to changes in coronary blood flow (CBF), myocardial contractility, and heart rate (HR) in 17 open-chest dogs. We developed a method of direct cannulation into subepicardial lymph vessels, which allowed us to study regional myocardial lymph circulation. Control values for the lymph flow rate (LF) ranged from 5.3 to 10.6 μ 1/ml. Adenosine, serotonin, histamine, and isoproterenol increased LF and protein efflux in cardiac lymph (PEF), and decreased protein concentrations (PC) concomitantly with coronary blood flow (CBF) increments. The relative increase of LF to CBF change was significantly greater upon administration of histamine and isoproterenol than with adenosine and serotonin. PC in the lymph were decreased by adenosine and serotonin, while no significant changes in PC were seen upon histamine or isoproterenol infusion. These results indicate that increased water release was greater than any protein efflux into cardiac with increased CBF, and that histamine and isoproterenol can modify capillary permeability directly or by changes in myocardial metabolism. An increased heart rate decreases LF and PEF possibly due to shortening of the diastolic time in the heart cycle.
Morphological changes in human basophils from atopic asthmatics were observed in whole blood smears with respect to histamine release after stimulation with antigen or anti-IgE. Histamine was rapidly released and was accompanied by morphological changes in basophils upon stimulation with antigen and anti-IgE. A decreased number of basophils and morphological changes including increased cell diameters, increased ratios of the short to long axis diameters, and decreased intracellular granule counts were observed upon the release of histamine after antigen and anti-IgE stimulation. Antigen stimulus induced both more rapid histamine release and morphological changes than anti-IgE stimulation.
Morphological changes in human basophils from 11 atopic asthmatics were observed in whole blood smears with respect to histamine release after the cells were challenged by Ca. ionophore A23187. A decreased number of basophils and granules in the cells as well as increase in cell diameters were observed upon histamine release after stimulation with Ca. ionophore A23187. Compared to cell reactions to antigen or anti-IgE, Ca. ionophore A23187 produced both more gradual morphological changes and histamine release and induced greater increases in the diameter of the basophils. No change in the ratio of the short to long axis diameter was observed after stimulation with Ca. ionophore A23187. The results suggest that basophils do not show any increased mobility upon stimulaion with Ca. ionophore A23187, though antigen and anti-IgE stimulation induces increased motility in these cells.
For purposes of quantitative detection of lung cancer-associated antigens in sera, a sandwich enzyme immunoassay was standardized. Four mouse monoclonal IgM antibodies (LA-3, LSI-4, LSI-a, and LSI-c) developed against human lung cancer cell lines were used for the assay. The 4 antigens in spent culture medium or cell extracts lost their antigenic reactivity after neuraminidase treatment, and the antigens were shown to be sialylated carbohydrate antigens. Serum antigen levels in 185 patients with malignancies, including 107 lung cancer patients, were measured and compared with those in 35 patients with benign respiratory diseases and 30 healthy donors. The levels of each antigen were significantly higher in the lung cancer patients than in patients with benign diseases or healthy donors. The percent of patients antigen-positive for each antigen was also significantly higher for lung cancer than with other diseases. Moreover, high antigen levels and antigen-positive rates were observed in hepatoma and pancreatic cancer patients. These results indicate that antigens detectable using these 4 antibodies are not lung cancer-specific, but may be useful in serum diagnosis of lung cancer as well as other malignancies.
To evaluate the clinical usefulness of four lung cancer-associated antigens ( LA-3, LSI-4, LSI-a, and LSI-c ), serum antigens in 107 patients with lung cancer and 35 patients with benign pulmonary diseases were measured quantitatively using a sandwich enzyme immunoassay. Pleural effusions from 20 lung cancer and 11 benign disease patients were assayed in the same manner. Mean levels of and positivity rates for each antigen in the sera of lung cancer patients were higher than in benigh diseases. Mean levels and positivity rates in stage III and IV lung cancer were significantly higher than those in stage I or II. Thus, diagnostic accuracy in lung cancer can be improved with combination assays for LA-3, LSI-4, and LSI-a. Each serum antigen level before and after chemotherapy changed according to the therapeutic effect. Indeed, the LA-3 antigen levels monitored in 3 lung cancer patients closely reflected the clinical course. Mean levels of and positivity rates for LA-3 and LSI-4 antigens in pleural effusions from lung cancer patients were significantly higher than for benign diseases. These results indicate that these 4 antigens detected in serum or pleural effusions can be clinically useful as tumor markers in lung cancer.
The purpose of this investigation was to determine the proportion of IgM Fc receptor bearing T lymphocytes (Tμ) and IgG Fc receptor bearing T lymphocytes (Tγ) in the peripheral blood of patients with juvenile rheumatoid arthritis (JRA). Peripheral lymophocytes from 20 patients with JRA and 20 normal controls were studied. Patients with JRA were classified into active and inactive groups, with 8 patients in the former and 12 patients in the latter. In 4 patients, methylprednisolone was injected intravenously in doses of 30mg/kg over 1 hr for 3 days. Peripheral blood lymphocyte subsets were evaluated before receiving the pulse, as well as 24 hours after the start of the 3rd infusion. The proportion of peripheral blood Tγ cells in the inactive group was significantly higher than in the active group (p<0.01). The Tμ/Tγ ratio of peripheral blood lymphocyte in the active group was significantly higher than that in the inactive group (p<0.01). Moreover, the proportion of Tγ cells increased significantly after injection of methylprednisolone for 3 days (p<0.01). These findings suggest that the proportion of Tμ and Tγ in the peripheral blood lymphocytes is of benefit in monitoring disease activity and prognosis of disease in JRA.
Electron beam therapy has often been used for radiation therapy of carcinomas of the buccal mucosa, though side effects including, stomatitis and dermatitis are known to exist. We experimented using the additional back scatter and transit with the phantom under a lead plate within the irradiation field, in order to better focus the dose on the target volume moreover, we fabricated a mouthpiece fitted with a lead plate shaped to the target volume, and with respect to the influence of the mouthpiece on stomatitis and dermatitis, obtained good clinical results.
Though numerous studies of systemic hemodynamics concerned with transient blockade of the portal vein exist, few studies have been performed specifically to assess blood flow and oxygen metabolism in the liver under such conditions. We blocked the portal vein in adult mongrel dogs and measured systemic hemodynamics, hepatic blood flow, total oxygen delivery to the liver, and the oxygen consumption and extraction ratio in order to evaluate the effect of a blockade of the portal vein on hepatic oxygen metabolism. In addition, a portal vein bypass was established and its effect on the liver was evaluated in comparison to a simple blockade of the portal vein. The results suggested that arterial blood pressure and cardiac output declined severely upon simple blockade of the portal vein, and a decrease in total hepatic blood flow which could be avoided by establishing a portal vein bypass was also observed. Simple blockade of the portal vein maximally accelerated the oxygen extraction ratio, though oxygen consumption by the liver significantly decreased due to insufficient oxygen supply caused by the decrease in blood flow in the hepatic artery. With a portal vein bypass, however, blood flow in the hepatic artery did not fall, oxygen consumption was maintained at a constant level, and a moderate rise in the oxygen extraction ratio was observed. These results indicate that establishing a portal vein bypass may be useful to protect the liver.
In order to investigate in detail the mechanism of late asthmatic responses (LAR) which seem to be involved in the development of intractable asthma, we prepared an experimental model of bronchial asthma using guinea pigs and examined neutrophil, eosinophil, and leukotriene (LTs) levels in venous blood and bronchoalveolar lavage fluid (BALF). Our results suggest that leukocytosis, and especially neutrophilia and eosinophilia is found in venous blood more with LAR than in IAR and non-attack states in control animals (P<0.01). Moreover, increased neutrophils were found in BALF in LAR compared with IAR and controls (P<0.01) and marked eosinophil infiltration was observed in the peribronchial tissue in LAR compared with IAR and control (P<0.01). Finally LTC4 levels were high in the venous blood and BALF in IAR, and LTB4 levels were also high in BALF in LAR. The data suggests that the accumulation of neutrtophils and eosinophils in peribronchial areas and release of leukotrienes in BALF play important roles in the etiology of LAR.
In investigating the etiological mechanisms of intractable asthma, ascaris suum was used as a sensitizing antigen in experimental animal models of re-inhalation in the late asthmatic response (LAR). Our results suggest that marked expiratory prolongation was caused by re-inhalation of the antigen in LAR. Moreover, the number of neutrophils and eosinophils increased in BALF after re-inhalation of the antigen more in LAR than in IAR (P<0.01). Finally the level of LTC4 and LTB4 increased in the venous blood and BABF after reinhalation during the LAR. The data suggests that cellular reactions among neutrophils, eosinophils, and other cells migrating into the airway lumen are seen in LAR, and moreover, LTC4 and LTB4 may be important chemical mediators in prolonged asthmatic attacks.