Some prognostic parameters influencing the progress of hepatitis to liver cirrhosis were investigated and evaluated retrospectively. The hepatitis patients, who had twice or more been performed peritoneoscopy at First Department of Internal Medicine, Okayama University Medical School, between 1958 and 1976, were selected. Fifteen patients out of 102 with smooth liver surface observed at the first peritoneoscopic examination progressed to liver cirrhosis. Higher progress rate of 37.9% (11cases of 29) was observed in HBsAg positive group, whereas a lower rate of 10.5% (4cases of 38) was observed in HBsAg and HBsAb negative group. No progress was observed in the 35cases of HBsAb positive group. Liver cirrhosis was highly advanced among youth in the HBsAg positive group, and highly advanced with age in both the HBsAg and HBsAb negative group. The former required less period of time to develop liver cirrhosis as compared to the latter. Higher rate of advancement to liver cirrhosis was observed in both the patient without hepatomegaly at the onset of disease and one with high TTT values and low blood plasma disappearance rate of ICG. The rate of advancement of hepatitis to liver cirrhosis was not correlated with presence of jaundice or splenomegaly, and changes of serum bilirubin, GPT, ZTT, and gamma-globulin values.
Changes in malondialdehyde (MDA) associated with convulsions were studied in El and ddY mice brain. Convulsions in El mice are easily induced by “tossing” stimulation. The brainstem MDA level in the interictal period of stimulated El mice was higher than in the non-stimulated control El mice. The MDA levels in the forebrain and cerebellum were lower after convulsions, but returned to the interictal period level 6 hours aftre convulsions. In the experimental status epileptics induced by ECS, the MDA levels in the brainstem and cerebellum were higher. The brainstem MDA level was also higher after daily maximal ECS for 8 days in ddY mice. The cerebellum MDA level was higher after ECS (10mA), and the brainstem was lower after ECS (7mA). In the case of pentylenetetrazol induced convulsions, the cerebellum MDA level was higher before convulsions, and the forebrain level was lower before, during and after convulsions. The brainstem level was also lower 30min after convulsions. In addition, the cerebellum level was lower during convulsions induced by dibenzoylguanidine (DBG), and the brainstem level was lower after convulsions by DBG. These results showed that generally the MDA level in the brain was lower after convulsions, but higher in particular brain regions after frequent convulsions, though experimental models of epilepsy and regional changes in MDA levels were different.
A simplified method of measuring the complex-release activity (CRA) of complement using peroxidase (PO) as an antigen in the immune complex was studied. PO-anti PO rabbit IgG immune complex (PO-IC) was solubilized principally via the alternative pathway in the sera. When substrates, H2O2 and 5-aminosalicylic acid, were added to solubilized PO-IC, absorbance of the mixture at O. D. 450nm increased with the amount of complement in a dose-dependent manner. The CRA of the complement in the sera was shown by the absorbance of the mixture. The CRA in various sera correlated with CH50. The CRA via the alternative pathway (ACRA) in sera also correlated with CRA, CH50 and ACH50. The above results indicate that this method of measuring the complex-release activity of complement using peroxidase as an antigen is simple and useful.
Complex-release activity (CRA) of complement was measured in 50 systemic lupus erythematosus (SLE) patients by a simplified method using peroxidase as an antigen in the immune complex. The relation between CRA and other complement levels was investigated, and the influence of CRA on the pathogenesis of SLE was discussed. CRA and ACRA (CRA via the alternative pathway) in SLE were lower than those in normal subjects. CRA and ACRA in SLE correlated well with CH50, ACH50, C3, C4 and factor B. The enhancement of CRA via the classical pathway in SLE was less strong than that in normal subjects. As reduced CRA normalized shortly after the administration of corticosteroid in some SLE patients with persistent hypocomplementemia, the measurement of CRA might be more useful than that of CH50 for clinical purposes. The above results suggest that the alternative complement pathway was activated by immune complexes in vivo and that CRA might play an important role in the clearance of immune complexes in vivo.
The effect of coronary sinus (CS) occlusion produced with a specially designed balloon catheter on coronary hemodynamics and ischemia-induced ventricular fibrillation was studied in anesthetized open-chest dogs. Heart rate (HR), aortic blood pressure (BP), left ventricular max dp/dt, coronary blood flow (CBF) and cardiac output decreased slightly with coronary sinus occlusion, while left ventricular end-diastolic pressure was not affected. These changes were attenuated but did not disappear, by pre-treatment with atropine. This result suggests that, at least partly, these changes were direct effects of venous congestion in the ventricular wall. CBF decreased in the diastolic, but increased in the systolic phase. Coronary sinus pressure (CSP) markedly increased especially in systole after CS occlusion, resulting in a pressure pattern resembling the left ventricular pressure pattern. The CSP exceeded the left ventricular pressure in the diastolic phase. Peak flow, reactive hyperemia flow, and repayment after a brief coronary artery occlusion were all decreased. Myocardial O2 extraction increased by about 9%, and the increase correlated well with the elevation of mean CSP. When the left anterior descending coronary artery was occluded, CS-occlusion increased retrograde pressure from 22±4mmHg to 33±7mmHg, and the incidence of ventricular fibrillation was decreased. Washout of the metabolites by retrograde flow from the ischemic myocardium would seem to be responsible for this reduction of ventricular fibrillation.
Effect of coronary sinus (CS) occlusion on pressure-flow relations was studied at paek reactive hyperemia in anesthetized open-chest dogs during vagal arrest. CS was closed by a specially designed balloon cather. The pressure-flow relations were lineal in both the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCX). With CS occlusion, the pressure-flow relations did not change in slope, but shifted to the right in both LAD and LCX. The zero-flow pressure intercept (PF=0) was 22±4mmHg in LAD, and 17±6mmHg in LCX with the CS open. There was no significant difference in The PF=0 between LAD ahd LCX. The PF=0 varied directly with changes in CS pressure caused by CS occlusion. Two Variables fitted closer in LCX than LAD. Even a slight elexation in CSP affected PF=0. Therefore, it is supposed that CSP worke as an extravascular compression rather than as a perfusion pressure.
β-Glucuronidase (β-G) and N-acetyl-β-glucosaminidase (NAG) activities were investigated in diabetic patients. Serum β-G activity, NAG activity, total cholesterol (TC), triglyceride (TG) and atherogenic index (A.I.) were significantly higher in diabetics than in controls. In diabetics, there were significantly positive correlations between serum β-G activity and fasting blood glucose level, TC, TG and A.I., and between serum NAG activity and fasting blood glucose level, TC and TG. Serum β-G and NAG activities were significantly higher in diabetics with hyperlipidemia than in diabetics without hyperlipidemia. The elevation of serum β-G and NAG activities in diabetics might be due to metabolic abnormalities accompanying hyperglycemia and hyperlipidemia. Serum NAG activity was significantly higher in diabetics with nephropathy than in those without nephropathy. β-G activity of polymorphonuclear leukocytes (PMN) in poorly controlled diabetics was significantly lower than PMN-β-G activity in controls and fairly controlled diabetics. Degradation of mucopolysaccaride and glycoprotein might be impaired in poorly controlled diabetics, and this impairment might explain glycoprotein-deposition in diabetic microangiopathy and impaired bacteriocidal activity in diabetic leukocytes. PMN-β-G activity was significantly higher in diabetics with severe diabetic retinopathy (ScottIII-V) than in those with mild diabetic retinopathy (Scott I-II). This data suggests that high PMN-β-G activity contributes to the establishment of diabetic microangiopathy.
β-Glucuronidase (β-G) and N-acetyl-β-glucosaminidase (NAG) activities in polymorphonuclear leukocytes (PMN) and serum were investigated in hyperlipidemia patients with or without hypertension or obesity. PMN-β-G and PMN-NAG activities were significantly lower in hyperlipidemia patients with hypertension and obesity than in those without these conditions. The data suggested that some functions of PMN were impaired in hyperlipidemia patients with hypertension and obesity. Serum β-G and NAG activities in hyperlipidemia patients were significantly higher than in controls, and increased with increases in serum total cholesterol, triglyceride and atherogenic index. Increases in serum β-G and NAG activities in hyperlipidemia patients, presumably were not related directly to atherosclerosis, but were probably related to metabolic abnormalities accompanying hyperlipidemia.
Three monoclonal antibodies, designated H-1, H-2 and H-3, were produced by immunizing BALB/C mice with cells of an established human null-acute lymphoblastic leukemia (NALL-1) cell line and fusing spleen cells from these mice with cells of a mouse myeloma cell line, P3-NSI/1-AG4-1. The resulting hybrid cells were initially screened for production of antibodies by complement-dependent cytotoxicity. Stable monoclonal antibody-producing cell lines were isolated by repeated cloning. These independently derived monoclonal antibodies showed complement-dependent cytotoxicities. Further characterization of the monoclonal antibodies was made by immunofluorescence. H-1 antibody reacted with all tested cells of the human nucleated cells except for HLA-lacking Daudi and K562 cells, and thus was shown to be specific for a common antigenic dererminant of HLA-A, -B and -C. H-2 antibody reacted with all of the tested null-cell lines, B-cell lines, B-cells and monocytes. Moreover, studies on fresh leukemia and lymphoma cells revealed that tumor cells from null-acute lymphoblastic leukemia, B-chronic lymphocytic leukemia and null-non-Hodgkin's lymphoma were H-2 antibody reactive. Cells from some patients with acute myelogenous leukemia, acute monocytic leukemia, chronic myelogenous leukemia in blast crisis and abult T-cell leukemia were also H-2-positive. In contrast, T-acute lymphoblastic leukemia, T-non-Hodgkin's lymphoma cells and mature T-cells did not react with H-2. A cross absorption study using H-2 and anti-HLA-DR monoclonal antibody confirmed the same specificity. Interestingly, H-2 showed blocking activities against the stimulation in one-way mixed lymphocyte culture. These results indicate that H-2 is a monoclonal antibody specific for a framework determinant of human Ia-like antigens. Reactivity of H-3 antibody was different from that of H-1 and H-2. H-3 reacted with some T-cells, B-cells and monocytes, suggesting that the antibody is associated with human leukocyte common antigens.
The effects of a thromboxane A2 synthetase inhibitor (OKY-046: sodium (E)-3-[4-(1-imidazolylmethyl)]-2-propenoate) on the diameter of normal and constricted basilar arteries and on the regional cerebral blood flow (r-CBF) in the brain stem after experimental subarachnoid hemorrhage (SAH) were investigated in 27cats. The basilar artery was exposed transclivally, and the change in its diameter was studied by serial photographs. Both normal and constricted basilar arteries showed only slight dilatation after an intravenous injection of OKY-046 (30mg/kg, 60mg/kg). Mean arterial blood pressure (MABP) decreased dose dependently with the administration of OKY-046. Exprimental SAH was produced by an intracisternal injection of 3ml of fresh autologous arterial blood. Three days later, the basilar artery was exposed transclivally, and an advanced prolonged vasospasm was produced by topical application of a blood-CSF mixture incubated at 37°C for 3days. The change in r-CBF in the brain stem was measured continuously by the heat clearance method before, during and after intravenous administration of OKY-046 (30mg/kg, 60mg/kg). The changes of r-CBF in cats with experimental SAH (n=9) were divided into three types: no change in r-CBF (n=3), a transient decrease in r-CBF related to the decrease in MABP (n=1) and an increase in r-CBF in spite of systemic hypotension (n=5). In 3 control cats, r-CBF decreased in relation to systemic hypotension. These results indicate that thromboxane A2 is not the major factor of cerebral vasospasm. However, OKY-046 which has been known to inhibit platelet aggregation and to prevent vascular constriction, might be useful in the prophylaxis and treatment of ischemic symptoms in patients with cerebral vasospasm.
The distribution of coenzyme Q10 (CoQ10) in serum lipoprotein fractions was measured by high-speed liquid chromatography during myocardial infarction and cerebral infarction. In control subjects, the major part of CoQ10 was present in the LDL fraction, and the distribution of CoQ10 was correlated with that of cholesterol. The CoQ10 level was related to the phenotypes of hyperlipidemias: more CoQ10 was present in LDL in type IIa, and in VLDL in types IIb and IV. In myocardial infarctions, the CoQ10 concentration decreased on the 3rd day, then gradually returned to the initial level in the serum and LDL fraction, while it decreased gradually untill the 21st day in the HDL fraction. The CO10-cholesterol ratio decreased on the 3rd day in serum, and on the 3rd, 7th and 14th days in the LDL fraction. In contrast, there was no significant change in the HDL fraction. In cerebral infarctions, the CoQ10 concentration decreased on the 3rd and 7th days in serum, and on the 3rd day in the HDL fraction. These results suggest that part of the metabolism of CoQ10 is the same as that of cholesterol in serum lipoproteins, and that CoQ10 is carried from LDL and HDL to mitochondria-rich organs during repair.
Myocardial necrosis was induced experimentally by the method of Rona, and coenzyme Q9 and α-tocopherol concentrations were measured in the serum and lipoprotein fractions. There was no significant change in the serum coenzyme Q9 concentrations after isoproterenol administration. In contrast, the serum α-tocopherol levels decreased 6h and 12h after the administration, and the α-tocopherol-cholesterol ratio decreased within 12h. In control subjects, most of coenzyme Q9 was distributed in the VLDL and LDL fractions, while most of α-tocopherol was present in the HDL fraction. The coenzyme Q9 levels decreased 6h, 12h and 24h after isoproterenol administration in VLDL, and the lowest level was at 12h. On the other hand, the coenzyme Q9 level elevated within 12h in the LDL fraction. The α-tocopherol level decreased rapidly in the VLDL fraction, reaching a minimum within 6h, and showed an increase at 12h in the LDL fraction. There was no significant change in the HDL fraction. The coenzyme Q9-cholesterol ratio increased within 12h in the LDL fraction and within 6h in the HDL fraction. The α-tocopherol-cholesterol ratio decreased within 6h in the VLDL and HDL fractions, while there was no significant change in the LDL fraction. The coenzyme Q9-α-tocopherol ratio increased within 6h in the VLDL and HDL fractions and within 12h in the serum and LDL fraction. These results indicate that the metabolism of coenzyme Q9 is different from that of α-tocopherol in lipoproteins. It is concluded that coenzyme Q is mainly transported from VLDL (and chylomicron) to LDL at the onset of acute vascular accidents, for the lipase activity is stimulated by hormones, and then coenzyme Q is carried from LDL and HDL to mitochondria rich organs through the LDL receptor or other routes.
Time factors of walking on level ground and slopes of 3, 6, 9 and 12 degrees were studied in eight normal adult men using foot switches. The greater the inclination of the slope, the less the cadence became. On the same slope, the downslope cadence was greater than the upslope cadence. The stance phase was longer when walking upslope (6, 9 and 12 degrees) and downslope (6 and 9 degrees) than when walking level. The double stance phase was longer when walking upslope (6, 9 and 12 degrees) than when walking level. Mid-stance was longer when walking upslope (3, 6, 9 and 12 degrees) and downslope (6, 9 and 12 degrees) than when walking level. The prolongation of the stance phase, double stance phase and midstance in slope walking compared with level walking was considered to be due to the instability of the center of gravity of the body and of the talo-crural and subtalar joints during slope walking. The time factors in normal adult slope walking is considered to be similar to those of children who have not yet acquired the adult walking pattern.
A case of primary systemic amyloidosis with various ECG abnormalities is reported. The ECG on admission showed low voltage in limb leads, right axis deviation, small q wave in leads I and aVL and QS configulation in V1 through V2. Conduction disturbances were observed in intra-atrial, A-V junctional and intraventricular conductions with frequent sinus arrest associated by A-V junctional escape beats. The heart sometimes fell into complete A-V block, infrequently with supernormal conduction. In spite of markedly abnormal ECG findings, amyloid infiltration in the mycoardium, His-bundle, A-V node and other discrepancies were minimum.
The localization of S-100 protein, a nervous system specific protein, was studied immunohistochemically in sections of normal human brain and various brain tumors. In human brain, the specific positive reaction for S-100 protein was observed in astrocytes, oligodendrocytes, ependymal cells and epithelial cells of the choroid plexus. In human brain tumors, a positive reaction was observed in all cases of astrocytoma, glioblastoma, oligodendroglioma, ependymoma, choroidplexus papilloma, neurinoma and teratoma examined. A positive reaction was also observed in some cases of meningioma and hemangioblastoma. In astrocytoma and glioblastoma, the positive reaction for S-100 proten was weak in intensity and heterogeneous throughout the section in accordance with the increased histopathological malignancy. All metastatic brain tumors were negative for S-100 protein. From this immunohistochemical evidence it is concluded that the immunohistochemical examination of S-100 protein in human brain tumors may become a useful method for the diagnosis of human brain tumors, especially in relation to the histogenesis and degree of malignancy.