Ribonuclease activities in liver tissue of patients with chronic liver diseases.
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Chronic Disease↗
Biomedical subjects
K Akagi
Publications and source records attributed to K Akagi.
Effects of recombinant leukocyte interferon on serum immunoglobulin concentrations and lymphocyte subpopulations in chronic hepatitis B.
To investigate immune effects of interferon (IFN) therapy in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, serum immunoglobulin concentrations and peripheral lymphocyte subpopulations were sequentially studied before, during, and after therapy in nine patients who were treated with recombinant human alpha-IFN in doses ranging from 3 to 10 million units per day for 28 days. Serum immunoglobulin A levels decreased significantly, from 414 +/- 23 mg/dl (mean +/- SE) to 379 +/- 28 mg/dl (P less than 0.05), after the first week of therapy and to a bottom value of 323 +/- 20 mg/dl (P less than 0.001) at the fourth week. Immunoglobulin G levels decreased significantly, from 2603 +/- 175 to 2328 +/- 169 mg/dl (P less than 0.005), after the first week of therapy and to a bottom value of 2005 +/- 199 mg/dl (P less than 0.001) at the fourth week. Immunoglobulin M levels were also reduced significantly after 3 weeks of therapy (from 229 +/- 23 to 188 +/- 15 mg/dl; P less than 0.01). These reductions in immunoglobulins A, G, and M returned to pretreatment levels by 4 months after the end of the therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Correlation of tissue-specific methylation with gene inactivity in hepatitis B virus transgenic mice.
We produced transgenic mice using two constructs, HB-GII and 1.2HB-BS, of hepatitis B virus (HBV) DNA. The former has been designed to express mRNAs for HBV surface antigen (HBsAg), and the later to express all mRNAs of HBV. Several lines of the transgenic mice carrying each construct were examined for the tissue-specificity and level of HBV DNA expression, and for the relationship between expression and methylation of the transgenes. Only one out of ten for HB-GII and one out of eight for 1.2HB-BS were high producers of viral antigens. In high producers, transgenes were expressed in the liver and the kidneys. But in low producers, transgenes were usually expressed only in the kidneys. There is a reciprocal relationship between the level of expression and the degree of methylation, that is, the higher the level of expression, the less the degree of methylation. We also observed that the expression of the integrated HBV-DNA was repressed by methylation following its passage through the female germline in one line. Thus, in addition to transacting factors that can control the gene expression positively or negatively, this tissue-specific methylation may also be involved in the regulation of HBV gene expression.
Animals↗
Threshold of hormonal and biophysical responses to acute hypoxemia in fetal sheep at different gestational ages.
We examined whether there was a threshold for change in fetal arterial PO2 to elicit alterations in plasma adrenocorticotropic hormone, arginine vasopressin, or cortisol, or to affect the incidence of fetal breathing movements or eye movements and we determined whether such a threshold changed with gestational age. Fetal sheep were exposed to two levels of hypoxemia, mild (4.6-5.3 mmHg PO2 drop) and moderate (8.3-8.8 mmHg PO2 drop) (1 mmHg = 133.322 Pa) for 1 h without pH change at 125-129 or 134-147 days of gestation within 7 days of spontaneous labor. Hypoxemia was induced by altering the inspired percent oxygen of the mother. No significant hormonal and biophysical changes were observed in mild hypoxemia at either age. In moderate hypoxemia at 125-129 days of gestation, there were significant increases of fetal adrenocorticotropic hormone, arginine vasopressin, and cortisol concentrations, and a decreased incidence of fetal breathing movements and eye movements. At 134-147 days of pregnancy, moderate hypoxemia induced a significant increase in adrenocorticotropic hormone, but the response was less than at 125-129 days of gestation. The arginine vasopressin response was similar to that at 125-129 days and there was no significant change in cortisol. There was a significant decrease in fetal breathing movements but not in eye movements. We conclude that a threshold of fetal arterial PO2 drop exists between 5 and 8 mmHg to elicit endocrine or biophysical responses to hypoxemia in fetal sheep at 125-129 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
Hormonal and biophysical responses to acute hypoxemia in fetal sheep at 0.7-0.8 gestation.
We examined whether there was a minimal change in fetal arterial Po2 necessary to elicit alterations in plasma adrenocorticotropic hormone, arginine vasopressin, or cortisol or to affect the incidence of breathing movements or eye movements in fetal sheep at 106-117 days of gestation. Fetal sheep were exposed to two levels of hypoxemia, mild (4.1 mmHg Po2 drop) (1 mmHg = 133.32 Pa) and moderate (8.4 mmHg Po2 drop), for 1 h without acidemia. Hypoxemia was induced by altering the inspired percent oxygen of the mother. No significant hormonal and biophysical changes were observed in mild hypoxemia. In moderate hypoxemia, there were significant increases of fetal adrenocorticotropic hormone and arginine vasopressin and decreased incidence of fetal breathing movements. However, there were no significant changes in cortisol or eye movements. We conclude that a fetal arterial Po2 drop of between 4.1 and 8.4 mmHg is necessary to elicit responses to hypoxemia in fetal sheep at 106-117 days of gestation in adrenocorticotropic hormone, arginine vasopressin, and fetal breathing movements, but this degree of hypoxemia does not cause changes in cortisol or fetal eye movements.
Adrenocorticotropic Hormone↗
Relationship between blood gas values and hormonal response to acute hypoxemia in fetal sheep.
We examined the relationship of fetal plasma immunoreactive adrenocorticotropic hormone (IR-ACTH), arginine vasopressin (AVP) and cortisol to fetal arterial pO2 (PaO2), oxygen saturation (SaO2), change (delta) in PaO2 (delta PaO2) or SaO2 (delta SaO2) in fetal sheep at 125-139 days of gestational age. Fetal sheep were exposed to two levels of hypoxemia induced by altering the inspired percent oxygen to the mother for 1 h without fetal acidemia. Fetal carotid arterial IR-ACTH, AVP and cortisol concentrations during hypoxemia were correlated with fetal PaO2, SaO2, delta PaO2 and delta SaO2 by applying simple regression analysis. For IR-ACTH, a strong correlation was obtained with SaO2, delta SaO2 and delta PaO2 after log transformation to IR-ACTH. For AVP, strong correlation coefficients were obtained with delta SaO2, SaO2, delta PaO2 and PaO2 after reciprocal transformation to AVP, but for cortisol a strong correlation was obtained only with delta PaO2 after log transformation to cortisol. We conclude that during fetal hypoxemia without acidemia, there is a strong correlation between IR-ACTH and SaO2, delta SaO2, delta PaO2 but not PaO2, between AVP and delta SaO2, SaO2, delta PaO2, or PaO2, and between cortisol and delta PaO2.
Acute Disease↗
[Asymptomatic infection of Legionella pneumophila in four cases with pulmonary diseases].
In view of the wide-spread existence of legionellae in cooling-tower and other environmental water, asymptomatic infection of this organism could occur. In order to verify the possibility of colonization of legionellae at lower respiratory tract of patients with various pulmonary diseases, a total of 22,036 sputum samples from in- and out-patients at National Sanyoso Hospital were examined during a five-year period from September, 1984 to August, 1989. Four (0.073%) out of 5,502 cases were culture-positive for L. pneumophila. L. pneumophila strains were isolated from expectorated, subsequently washed sputum samples of two male and two female patients with respiratory tract diseases. The identification of the isolates was genetically confirmed by the fluorometric microplate DNA-DNA hybridization method. The serogroup (SG) and viable counts of L. pneumophila per ml of sputum of each patient were as follows: 73 y/o female K.H., SG-6, 10(3) CFU; 75 y/o male H.J., SG-5, 10(4) CFU; 61 y/o female M.S., SG-5, 10(5) CFU; and 77 y/o male M.G., not-agglutinable against SG-1-6 antisera, 10(4) CFU. None of the four patients was clinically suspected of legionellosis and antibody titer of paired sera remained 1:64 or lower than 1:32. From these findings, we concluded that L. pneumophila can cause, though quite rarely, asymptomatic infection in human respiratory tract. None of the environmental samples obtained from in- and out-side of the Hospital was culture-positive for legionellae. Thus, the source of infection has remained unknown.
Aged↗
Clinical application of a static splitting agent for removing the denture from its cast after curing.
A very effective method for removing a denture from its cast after curing has been developed using a static expansive agent for hydration. Three filling hole designs for packing the expansive agent into a stone cast were examined to obtain the most effective method of splitting the cast for clinical application. The dynamic strain in the resin denture base was measured during static splitting one filling hole design was the safest for handling and the most effective for removing the denture. The upper tolerance limits for the maximum strain were estimated to be 2.9 x 10(-3) in the upper denture and 3.4 x 10(-3) in the lower denture. These values were lower than one-third of the critical strain corresponding to the proportional limit of the denture resin.
Calcium↗
Cortisol inhibits ACTH but not the AVP response to hypoxaemia in fetal lambs at days 123-128 of gestation.
During acute hypoxemia in fetal sheep the elevation in ACTH concentration in the fetal circulation at days 125-129 is greater than that at term, but similar rises in AVP occur at both times. To examine whether the diminished ACTH response is due to elevated endogenous cortisol, and if there is differential control of ACTH and AVP release in hypoxemia, we infused either vehicle or cortisol (5 micrograms/min) into fetal sheep at days 123-128 for 5 h before and then during a 2-h period of acute hypoxemia (mean PaO2 decrease 8.2 mmHg) without acidemia. During cortisol infusion, plasma cortisol rose to 40-50 ng/ml, similar to values in term fetuses. In vehicle-infused fetuses, cortisol rose from 2.1 to 7.0 ng/ml at +1 to +2 h of hypoxemia. ACTH rose significantly during hypoxemia in the vehicle-infused fetuses, and this response was attenuated by cortisol infusion. In contrast, fetal AVP rose significantly during hypoxemia both in the presence and absence of cortisol infusion. Fetal breathing movements, and electroocular activity decreased during hypoxemia, and these responses were not altered by cortisol. We conclude that cortisol exerts differential negative feedback on ACTH but not on AVP release during hypoxemia. The maintained AVP response may facilitate cardiovascular adjustments of the fetus to hypoxemia even when endogenous cortisol is elevated, such as near term.
Adrenocorticotropic Hormone↗
[Analysis of cell kinetics using BrdU monoclonal antibody on cultured tumor cells after irradiation and treatment with anti-cancer drugs].
Flow cytometry (FCM) permits instantaneous determination of the percentages of cells in various phases of cell cycle using BrdU-PI double staining method, and allowing rapid evaluation of the effects of irradiation and anti-cancer drugs (ACNU, ADR, BLM) on the cell kinetics. In this study, the growth inhibition and changes in the cell kinetics after irradiation and chemotherapy were examined according to the growth curve analysis and BrdU-PI method to evaluate the usefulness of BrdU-PI method for assessment of the effect of the treatments. By the conventional method based on the DNA histogram, accurate determination of S cell fraction was difficult due to overlapping of the DNA contents of G1 cells and early S cells and those of late S cells and G2 cells. BrdU-PI double staining allowed direct differentiation of G1, S, and G2 + M cells, especially between G1-S and S-G2 + M cells. The analysis of cell kinetics using BrdU is advantageous in comparison to the conventional autoradiographic methods because it allows more rapid assay with very high sensitivity. By the present BrdU method, rapid transition to the G1-S phase was observed within 4 hours after exposure to radiation and anti-cancer drugs. This initial G1 arrest induced by irradiation was confirmed for the first time by the present BrdU-PI double staining. The present method is considered to be indispensable for evaluation of the percentage of S cells in the tumor tissue and analysis of cell kinetics after irradiation and chemotherapy against cancer.
Antibodies, Monoclonal↗
Multiple myeloma associated with Budd-Chiari syndrome.
A 51-year-old Japanese woman with Budd-Chiari syndrome, following dermatoplasty of the leg for burns, developed multiple myeloma and amyloidosis during the four-year observation period. In Budd-Chiari syndrome, polyclonal hypergammaglobulinemia is frequently seen as the result of intestinal antigenic stimulation through the portacaval shunt. Although monoclonal gammopathy is occasionally presented in chronic liver diseases, multiple myeloma has not been previously recognized as occurring in association with Budd-Chiari syndrome. This case demonstrates that, in Budd-Chiari syndrome, the development of multiple myeloma may be the result of chronic stimulation of the intestinal microbes.
Budd-Chiari Syndrome↗
[A case of hepatocellular carcinoma associated with chronic renal failure on haemodialysis].
A 36 years old man with chronic renal failure on haemodialysis therapy presented with a hepatic mass which was diagnosed by ultrasonography, and was admitted to our hospital. Computer tomography and hepatic angiography revealed hepatocellular carcinoma of the right anterior superior segment of the liver. His liver function test, alpha-fetoprotein (AFP) and carcinoembryonic antigen levels in the serum were within the normal range. HBs antigen was also negative. Resection of right antero-superior segment was done following transcatheter arterial embolization. The tumor was homogeneous and light yellowish in color, and well demarcated by the capsule. Nontumorous tissue did not show either fibrosis or any inflammatory reaction. In general, hepatocellular carcinoma is associated with a positive HBs antigen and altered liver function. We here report a rare case of hepatocellular carcinoma in a man who was undergoing haemodialysis treatment for chronic renal failure with normal liver function test and negative HBs antigen.
Adult↗
Effects of recombinant leukocyte interferon on ribonuclease activities in serum in chronic hepatitis B.
Alkaline ribonuclease (RNase; EC 3.1.27.5) activities and 2',5'-oligoadenylate synthetase (2-5 AS; no EC no. assigned) activities in serum were measured in nine patients with hepatitis B e antigen-positive chronic hepatitis B before, during, and after treatment with recombinant human interferon alpha-2b for four weeks at daily doses ranging from 3 to 10 mega-units. Alkaline RNase activities in serum significantly increased from 65.8 +/- 9.5 units/L (mean +/- SD) to 84.3 +/- 11.9 units/L after the first week of therapy (P less than 0.001). (One unit of RNase activity is defined as that increasing the absorbance at 260 nm by 1.0 in 1 min). This increase persisted during and until two weeks after the end of the therapy, at which time the mean RNase activity in serum was still significantly increased (70.8 +/- 9.4 units/L, P less than 0.01). Before therapy, phosphocellulose chromatography of RNase showed five active peaks of enzyme activity, which were similar to that observed even when RNase activity increased immediately after therapy. There was a close correlation between RNase activities and the logarithm of 2-5 AS activities, measured simultaneously in each patient. We conclude that recombinant alpha-interferon therapy increases RNase activities in serum, associated with the increased 2-5 AS activities.
2',5'-Oligoadenylate Synthetase↗
[A case of alcoholic cirrhosis demonstrating long-term poor-visualization of the hepatic image on 99mTc-phytate scintigraphy].
A 27-year-old female patient with alcoholic cirrhosis was reported. She was admitted to the hospital because of jaundice and ascites after heavy drinking. She had a history of drinking Japanese Sake in quantities of more than 5 go/day (900 ml/day) for 7 years. On admission, she was icteric, and had both hepatosplenomegaly and ascites. Laboratory data showed an elevation of serum transaminase and bilirubin, and a decrease in the albumin and prothrombin values. A biopsy specimen of the liver showed pericellular fibrosis, fatty change, Mallory bodies and regenerative nodules, and revealed findings compatible with alcoholic cirrhosis. A 99mTc-N-pyridoxyl-5-methyltryptophan scintigram showed hepatomegaly. On the 99mTc-phytate scintigram, the uptake of radioisotope to the liver was markedly decreased with the increased uptake to the spleen and bone marrow. Even 6 months after the onset, poor visualization of the hepatic image on 99mTc-phytate scintigram continued. This is the first report of alcoholic cirrhosis demonstrating a long-term poor visualization of the hepatic image on 99mTc-phytate scintigraphy.
Adult↗
[Analysis of cell kinetics after irradiation by flow cytometry (II)--Evaluation of clonogenic potential of G2 block cells after irradiation by cell sorting].
When the tumor cells are irradiated, the percentage of the cells in the G2 + M phase and the duration of the cell cycle arrested increase with the irradiation dose. This post irradiation growth inhibition and changes in the cell kinetics observed within 48 hours of irradiation are closely correlated. Cells in the G2 + M phase are reported to be sensitive to irradiation, but little is known about their clonogenic potential. These cells must be separated for evaluation of their clonogenic potential. In this study, the clonogenic potential of irradiated G2 phase arrested cells was examined by the flow cytometric cell sorting technique. Fluorescent Hoechst staining, which allows determination of DNA content in living cells, was used. The results of DNA assay using Hoechst 33342 agreed well with those using PI staining. The concentration of Hoechst 33342 required for the DNA assay and cell sorting is 5 micrograms at which vital staining is possible with 80% cell viability. Although the clonogenic potential of non-irradiated cells was not different between those in G1 and G2 + M phases, that of the cells arrested in the G2 + M phase after irradiation was lower than that of the cells in the G1 phase. The reduction in the clonogenic potential was more notable in the cells subjected to high dose irradiation. A greater number of cells were arrested for a longer period than the cells irradiated at a lower dose. The clonogenic potential of the cells correlated well with the duration of G2 block.
Cell Separation↗
Strain dependency of B and T lymphoma development in immunoglobulin heavy chain enhancer (E mu)-myc transgenic mice.
The transgenic mice were produced by injecting eggs of B6 and C3H/HeJ mice with the human E mu-myc gene. Preferential development of B lymphomas was observed in the B6 transgenic mice, whereas the C3H/HeJ transgenic mice developed mostly T lymphomas. The phenotypic activation of B lineage cells but not of T lineage cells was detected in the prelymphomatous transgenic mice of both strains. The transgene was similarly expressed in B and T cells of the transgenic mice of both strains. These results suggest that a high incidence of T lymphomas in the C3H/HeJ transgenic mice may not be due to the preferential activation of or the preferential E mu-myc expression in T lymphocytes. When the bone marrow or fetal liver cells from the prelymphomatous transgenic mice of both strains were transferred into irradiated normal C3H/HeJ mice, most of the recipients developed T lymphomas. Moreover, even when irradiated B6 mice received the hematopoietic stem cells from the prelymphomatous B6 transgenic mice, the incidence of T lymphoma increased up to 50%. These findings suggest that B6 and C3H/HeJ mice might provide the environment that supports the development or growth of B and T lymphomas, respectively, and that such an environment could be modified by irradiation of the mice.
Animals↗
[Analysis of cell kinetics after gamma ray irradiation using anti-BrdU monoclonal antibody].
The cell cycle was analyzed using anti-BrdU monoclonal antibody, and changes in cell kinetics after gamma ray irradiation as evaluated by this BrdU-PI double staining were compared with those evaluated by the DNA histogram method based on PI staining. The effect of irradiation on the cell kinetics has been studied according primarily to the number of G2 blocked cells. By the present BrdU method, rapid transition of the G1-S phase was observed within 2 hours of irradiation, and then G1 block was observed. Cells in the S phase progressed to the G2 + M phase, in which they were arrested, resulting in a decrease in the percentage of S cells to 5% or less. After 8 hours, release of G1 block was observed, and G2 + M cells returned to the G1 phase after 18 or more hours. These initial G1 blocked cells induced by irradiation were confirmed for the first time by the present BrdU-PI double staining. By the conventional method based on the DNA histogram, accurate determination of S cell fraction was difficult due to overlapping of the DNA contents of G1 cells and early S cells and those of late S cells and G2 cells. On the other hand, BrdU-PI double staining allowed direct differentiation of G1, S, and G2 + M cells, especially between G1-S and S-G2 + M cells. The analysis of cell kinetics using BrdU is advantageous over the conventional autoradiographic methods in that it allowed more rapid assay with very high sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Monoclonal↗
Spontaneous histamine release and histamine content in normal subjects and subjects with asthma.
Spontaneous histamine release (SHR) from basophils by simple incubation at 37 degrees C for 60 minutes and histamine content of basophils were assessed in normal subjects, patients with asthma, and methacholine-sensitive subjects without asthma (NAMS). SHR from basophils of normal subjects did not exceed 10% of the total histamine. A significantly higher SHR was observed in basophils from subjects with asthma than from normal subjects (p less than 0.002). Basophil SHR in patients with asthma not receiving medication was significantly greater than that in patients with asthma receiving medication (p less than 0.05). SHR from basophils in NAMS subjects was similar to that in normal subjects. SHR was highly dependent on temperature and Ca++ and Mg++ ions and appeared to be a slower event than anaphylactic release. The mean histamine content per basophil from normal subjects was 1.48 +/- 0.13 pg (mean +/- SEM). Basophils from subjects with asthma contained significantly less histamine than basophils from normal subjects (p less than 0.002). Histamine content per basophil from NAMS subjects was slightly lower than histamine content per normal basophil. No apparent relationship was found between the magnitude of SHR and the histamine content per basophil in the patients with asthma not receiving medication. Hypersensitivity to food or exercise does not appear to be essential for high SHR. High SHR appears to bear little, if any, relationship to cell damage or cell death. High SHR may be a factor that could serve as a marker for bronchial asthma. Further studies are needed to define the clinical relationship and pathophysiologic mechanism of SHR.
Adolescent↗