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Biomedical subjects

K Akagi

Publications and source records attributed to K Akagi.

At least 19 recordsLinked to original sources

[Hydralazine-induced enhancement of hyperthermia treatment in vivo].

Hydralazine (Hyd) is a vaso-active drug that significantly affects the nature of blood flow in tumors. As a result, Hyd reduces blood flow and oxygen tension in tumors, causing an increase in the toxic effect of hyperthermia treatment. We investigated enhancement of the anti-tumor effect of hyperthermia by Hyd on SCC-VII tumors in C3H mice. Hyd was administered by intraperitoneal injection, and tumors were heated by water bath. We measured the tumor temperature in animals receiving Hyd by thermocouple. We found no significant change in tumor temperature with Hyd treatment. The effect of Hyd (2.5 mg/kg, 5.0 mg/kg, 7.5 mg/kg) on tumors was evaluated in terms of a growth delay value at which tumor volume reached four-fold. The growth delay values obtained were 6.25 +/- 0.82, 7.14 +/- 0.90, 8.50 +/- 0.98, 9.72 +/- 0.92, and 9.84 +/- 1.3 days for: hyperthermia alone, Hyd of 1.0 mg/kg, 2.5 mg/kg, 5.0 mg/kg, respectively. This effect was independent of the time course of administration of Hyd. These results indicate that Hyd can increase the therapeutic efficacy of hyperthermia treatment. Changes in the microenvironment, such as low pH and tumor hypoxia, induced by arterial embolization may have increased the sensitivity of tumors to heat.

Animals

[Evaluation of thermal damage after hyperthermia on murine experimental tumor by 31P-NMR spectroscopy--correlation between ATP and growth curve].

The possibility of using 31P-NMR spectroscopy (31P-MRS) to estimate the effect of hyperthermic treatment on mouse FM3A tumor was investigated. 1 x 10(6) cells, suspended in saline, were subcutaneously inoculated to the right thigh of C3H mice. For hyperthermic treatment, the tumor-bearing leg was heated by immersing it in a water bath at 44 degrees C for 10, 20 or 30 min. The signal intensities of ATP and Pi of the tumor were measured utilizing the 31P-MRS technique to calculate the ATP/Pi ratio. Immediately after heating, the ATP/Pi ratio decreased markedly. Eighteen hours after hyperthermic treatment, the ratio recovered but was still smaller than the control value, then became almost constant by 24 hours after heating. The ATP/Pi ratio at 24 hours after heating decreased with increased length of heating and was inversely related to tumor regrowth after hyperthermic treatment. We concluded that non-invasive monitoring with 31P-MRS might provide a good indication of the effect of hyperthermic treatment.

Adenosine Triphosphate

Selective deficiency of C1s associated with a systemic lupus erythematosus-like syndrome. Report of a case.

We describe a patient who developed a systemic lupus erythematosus-like syndrome characterized by bilateral malar erythema, antinuclear antibody, and anti-double-stranded DNA antibody. He was started on hemodialysis (3 times/week) because of renal failure. He completely lacked total hemolytic complement (CH50) activity, which was subsequently determined to be due to the absence of the first component of complement (C1). The specificity was further defined, by Ouchterlony analysis using anti-C1s antiserum, and was found to be the C1 subcomponent C1s. There was no absence of C1r. We conclude that this is a case of selective deficiency of C1s.

Adult

Familial primary biliary cirrhosis associated with impaired concanavalin A-induced lymphocyte transformation in relatives. Two family studies.

The familial occurrences of biochemical and immunological abnormalities and histocompatibility antigens were studied in 18 healthy first-degree relatives of patients with primary biliary cirrhosis (PBC) in two families. In each of these two families, there were two members who suffered from PBC. All relatives had normal serum aspartate aminotransferase, alkaline phosphatase, bilirubin, total cholesterol, and immunoglobulins except the two, who had a mild elevation of alkaline phosphatase without cholestasis. Autoantibodies were present in some relatives; five (28%) for antithyroglobulin antibody and antithyroid microsomal antibody, one (6%) for antimitochondrial and antinuclear antibody, and one (6%) for rheumatoid factor. Abnormalities of T or B lymphocytes in peripheral blood were detected in two (11%) relatives. Impairment of concanavalin A-induced lymphocyte transformation determined by ethidium bromide fluoroassay was found in seven (39%) relatives, although an abnormal response for phytohemagglutinin was detected in none of the relatives. The HLA haplotypes were not necessarily associated with positive autoantibodies or impaired concanavalin A-induced lymphocyte transformation in these families. These findings suggest that impairment of concanavalin A-inducible lymphocytes (mainly suppressor T cells) is one of the contributing factors in the development of PBC.

Adolescent

Change in electrocardiogram T-wave amplitude during umbilical cord compression is predictive of fetal condition in sheep.

OBJECTIVE: The purpose of this study is to assess the usefulness of the dynamic change in T/QRS ratio in fetal electrocardiograms in predicting the fetal condition when repetitive variable decelerations are seen in intrapartum cardiotocograms. STUDY DESIGN: We investigated the relationship, using linear regression and Wilcoxon's test, between T/QRS and blood gas values, catecholamine concentrations, and blood pressure during repetitive cord compression in five chronically instrumented lamb fetuses. RESULTS: T/QRS during cord compression correlated significantly (p less than 0.01) with fetal arterial pH (r = -0.7711), norepinephrine concentration (r = 0.7551), and duration of elevated blood pressure during compression (r = -0.8619). Fetal arterial pH and base excess were lower, the duration of elevated blood pressure during compression was shorter, and carbon dioxide partial pressure and catecholamine concentrations were higher in the stage with higher (greater than 0.50) T/QRS during compression (p less than 0.005). CONCLUSION: We can estimate the severity of fetal distress by measuring T/QRS near the bottom of the decelerations.

Animals

Properties of test metal ceramic titanium alloys.

Four test alloys were prepared using a high frequency centrifugal casting machine and a ceramic crucible for the development of titanium bonding alloys that can be cast in the ordinary atmosphere. Of these alloys, 10.06% Ti, 78.79% Ni, 9.02% Pd, 1.77% Sn and 9.91% Ti, 78.56% Ni, 9.07% Pd, 1.86% Sn, 0.65% Ir could be cast by the conventional high frequency centrifugal method; however, 89.18% Ti, 8.75% Ni, 1.03% Pd, 0.28% Sn and 89.81% Ti, 8.15% Ni, 1.01% Pd, 0.18% Sn, 0.67% Ir could be cast only by the argon are melting method. The alloys 10.06% Ti, 78.95% Ni, 9.02% Pd, 1.77% Sn and 9.91% Ti, 78.56% Ni, 9.07% Pd, 1.86% Sn, 0.65% Ir showed excellent physical and mechanical properties and bonding strengths, surpassing those of the commercial alloys TPW and Unimetal. Concerning the elution of component elements, the amounts of titanium eluted from these alloys were far smaller than those from pure titanium or a Ti-6Al-4V alloy, and nickel elution, which has become an issue in relation to metal allergy, was almost nil in contrast to Unimetal (Ni-Cr alloy). The alloy 9.91% Ti, 78.56% Ni, 9.07% Pd, 1.86% Sn, 0.65% Ir showed properties that indicated its favorable use as an alloy for the bonding of dental porcelain.

Adhesiveness

Transfusion-associated graft-versus-host disease in a presumably immunocompetent patient after transfusion of stored packed red cells.

A 54-year-old woman developed transfusion-associated graft-versus-host disease (TA-GVHD) after the transfusion of stored packed red cells obtained from unrelated donors. The patient was presumed to be immunocompetent. A diagnosis of TA-GVHD was made by clinical features and postmortem pathologic findings. Sex chromatin analysis of the patient's lymphocytes demonstrated chimerism. HLA typing of the blood donors revealed one to be HLA-homozygous for one of the patient's HLA haplotypes (A33-B44-Cblank). This case illustrates the risk in the general patient population of TA-GVHD after routine blood transfusion therapy. Workers should be aware of this possibility and should continue searching for an efficient way to prevent it.

Blood Component Transfusion

Strain dependency of cell-type specificity and onset of lymphoma development in Emu-myc transgenic mice.

c-myc is a nuclear proto-oncogene that, when activated, induces malignancies in a variety of tissues. Most murine plasmacytomas and human Burkitt's lymphomas have been shown to carry a chromosomal translocation involving c-myc and immunoglobulin genes. To study genetic or epigenetic factors that affect myc-induced lymphoid cell tumors, we previously introduced the Emu-myc delta gene lacking its own promoter and first exon into two inbred strains of mice, C57BL/6 and C3H/HeJ. We observed three characteristic features in our transgenic mice. First, T cell lymphoma predominated in the C3H background. Second, both pre-B and B cell lymphoma developed at equal frequency in C57BL/6 transgenic mice. Third, the average age of onset is earlier than that reported by other investigators. To test whether these characteristics are due either to the lack of the promoter region and first exon of the c-myc gene in the construct or to the genetic background of the mice, we introduced Emu-myc gene containing the complete c-myc gene into fertilized eggs of C57BL/6 and C3H/HeJ mice. The cell-type specificity, differentiation-stage specificity and the average age at onset of lymphoma development were not affected by the transgene construct.

Age Factors

Femoral artery blood flow monitoring has distinct advantages for examining redistribution of blood flow in fetal acidosis.

Changes of blood flow in umbilical artery, carotid artery and femoral artery were examined during the progression of acidemia in fetal sheep by means of indwelling transit-time ultrasonic blood flow meters. Moreover, catecholamines in fetal blood were measured and its interrelation to the alteration in blood flow was examined. Gradually progressing fetal acidemia was induced by repeated cord compression. Umbilical blood flow showed a initial increase thereafter maintaining a plateau through the experiment, which seemed to be dependent on fetal arterial pressure. Carotid artery flow gradually increased until the arterial pH in fetal blood declined to 7.20 and remained at this level even though the acidemia further progressed. Femoral artery flow markedly decreased around fetal arterial blood pH 7.20 and its change correlated well with the plasma level of catecholamines. This change of femoral artery flow may be evaluated by examination of the flow index as well as flow volume. Redistribution of blood flow in the progression of fetal acidemia may be initiated at around fetal arterial pH 7.20 and can be detected by studying femoral artery flow.

Acidosis

[A case of idiopathic hemochromatosis associated with gastric cancer].

A 76-year-old male was admitted to our hospital because of general fatigue in June 1987. He had received total gastrectomy against gastric carcinoma two years previously. The examinations revealed the elevation of GOT, GPT and gamma-GTP, and increased CT number of the liver. Specimen of the liver biopsy showed deposition of iron and slight fibrosis. He was diagnosed as idiopathic hemochromatosis. He was given deferoxamine, and his elevated GOT, GPT and gamma-GTP were normalized. Idiopathic hemochromatosis is frequently associated with various malignancies including hepatic carcinoma. However, only a few cases of idiopathic hemochromatosis associated with gastric carcinoma have been reported.

Adenocarcinoma

[Proposal of a new classification of adult bronchial asthma--child onset asthma, adult onset asthma and adult relapse asthma. Project Team for Research into Adult Bronchial Asthma in Japan].

The first nationwide research into adult bronchial asthma in Japan proposed a new classification of adult asthma. Adult asthma was categorized into child onset asthma, adult onset asthma and adult relapse asthma. The frequency of child onset asthma, adult onset asthma and adult relapse asthma in adult asthma was 11.2%, 77.3% and 3.7%, respectively. The frequency of child onset asthma decreased markedly in the older age group. On the other hand, the frequency of adult onset asthma increased, and reached more than 90%, in the older age group. The frequency of the following factors: atopic asthma, complications with other atopic diseases, mild asthma, male patients, experience of mechanical ventilation, visits to night clinics and oxygen therapy on acute attack, was significantly higher in the child onset asthma group than in the adult onset asthma group. The frequency of infectious type, aspirin intolerance, steroid dependent asthma, severe asthma and regular medication was significantly higher in the adult onset asthma group. Adult relapse asthma seemed to fall between these two groups. Based on the above observations, we proposed a new classification of adult asthma which includes child onset asthma, adult onset asthma and adult relapse asthma.

Asthma

[Flow cytometric analysis of chromosome aberration on tumor cells].

Chromosomal changes plays an important role in malignant transformation. Generally, the process of karyotype instability with grows aneuploidy occurs in tumor. But it is very difficult to obtained Flow karyotype from tumor cells. There are many technical problem in the analysis of chromosomes aberration in tumor cells. Problem is technical procedure of isolation from metaphase chromosomes. It is important to choice of swelling buffer and treatment times. Such technic affect for Flow karyotype pattern. We try to obtained Flow karyotype from chinese hamster cell and V-79 cells and we reported a recent new techniques of cell preparation and chromosomes suspension.

Aneuploidy

Comparison of the properties of ribonucleases in human liver tissue and serum.

Two ribonucleases (RNases) with acidic pH optima were partially purified, one from normal human liver tissue and the other from serum. The properties of the two enzymes were studied and compared. Liver RNase was partially purified about 700-fold by acid fractionation, phosphocellulose column chromatography, Sephadex G-75 gel filtration, and polyguanylate affinity column chromatography. Serum RNase was purified about 1200-fold by phosphocellulose column chromatography and Sephadex G-75 gel filtration. The two RNases showed a similar optimal pH and molecular mass, and similar behaviour towards metal ions, but they differed in their substrate specificity. Liver RNase displayed a higher activity towards polyuridylate (poly(U)) than towards polycytidylate (poly(C)), while serum RNase hydrolysed poly(C) more rapidly than poly(U). These findings suggest that liver RNase is not the primary source of the serum RNase with an acidic pH optimum.

Cations

Exposure to hepatitis B virus in the general population of Hisayama, Japan: significance of isolated antibody to hepatitis B surface antigen in general population.

Cross-sectional survey on the prevalence of hepatitis B serological markers was performed in 2,411 residents who accounted for 74.4% of the population aged 40 and over and living in Hisayama Town, Japan, in 1983. Overall prevalences were 40.7% for both anti-HBs and anti-HBc, 6.1% for isolated anti-HBs and 5.4% for isolated anti-HBc. The condition with isolated anti-HBs was different from those with isolated anti-HBc and both anti-HBc and anti-HBs as follows. The titer of anti-HBs in isolated anti-HBs positive samples was significantly lower than that in both anti-HBs and anti-HBc positive ones (46.2 +/- 5.4 vs. 83.2 +/- 2.8, mean +/- SE, p less than 0.001). The presence of isolated anti-HBs was neither significantly more frequent in males nor related to the risk of liver damages in contrast with that of anti-HBc with or without anti-HBs. These findings suggest that isolated anti-HBs pattern with the absence of anti-HBc in general population was not due to prior HBV infection, but due to natural immunization with HBsAg.

Adult

Prevalences of hepatitis B surface antigen carriers and liver damages in the general population of Hisayama, Japan.

The prevalences of hepatitis B surface antigen (HBsAg) carriers and liver damages were studied in 2,411 residents aged 40 and over and living in Hisayama, Japan in 1983. Hepatitis B virus (HBV) associated markers were all measured by radioimmunoassay. HBsAg carriers were found in 2.3 per cent of the residents. Hepatitis B e antigen and antibody to hepatitis B e antigen were positive in 8.9 per cent and 80.4 per cent, respectively, of HBsAg carriers. The prevalences of liver damages in HBsAg carriers were compared with 1095 who had none of HBV markers (neither anti-HBc nor anti-HBs). The prevalences of abnormal aminotransferase level in sera were not different between HBsAg carriers and those who had none of HBV markers. A history of jaundice and/or hepatitis was evident in 32.3 per cent of male carriers and 24.0 per cent of female ones, being significantly more than those without HBV markers (13.1 per cent and 5.8 per cent, p less than 0.05 and p less than 0.005, respectively). These results indicate that, among HBsAg carriers aged 40 and over, few have active clinical signs of hepatitis, although about 20 per cent of them have histories of symptomatic hepatitis due to hepatitis B.

Adult

Specific depletion of the B-cell population induced by aberrant expression of human interferon regulatory factor 1 gene in transgenic mice.

Interferons (IFNs) are well known both as antiviral proteins and as potent regulators of cell growth and differentiation. In fact, IFNs inhibit growth of various normal and transformed cell types. Previously, a nuclear factor, IRF-1 (interferon regulatory factor 1), which binds to type I IFN and some IFN-inducible gene promoters, was identified and cloned. Since the IRF-1 gene is both virus and IFN inducible, an intriguing issue is raised as to whether the IRF-1 gene is functioning in IFN-mediated regulation of cell growth and differentiation. In this study, we generated transgenic mice carrying the human IRF-1 gene linked to the human immunoglobulin heavy-chain enhancer. In the transgenic mice, all the lymphoid tissues examined showed a dramatic reduction in the number of B lymphocytes (B cells). Preparation and analysis of bone marrow cells from the chimeric mice indicated that the bone marrow is the effective site for specific depletion of the B-cell population. In fact, transgenic bone marrow cells cocultured with a bone marrow-derived stromal cell line revealed an altered B-cell maturation pattern.

Animals

Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin.

During B cell differentiation, at least three stages can be defined in terms of their growth signal requirement by using two different growth signals, which are recombinant interleukin 7 (IL-7) and a stromal cell clone PA6 which does not produce IL-7; first a PA6 dependent stage, second a PA6 + IL-7 dependent stage and third an IL-7 dependent stage. In order to test the possibility that this differentiation of growth signal requirement is controlled by the expression of functional immunoglobulin molecules, we have investigated the frequencies of PA6 + IL-7 dependent and IL-7 dependent cells which are present in the bone marrow of either mu-chain or kappa-chain gene transgenic mice. In a mu-chain gene transgenic mouse, the frequency of PA6 + IL-7 dependent cells is selectively reduced, while that of IL-7 dependent cells is selectively reduced in a kappa-chain gene transgenic mouse. This result suggests that expression of a functional mu-chain gene drives PA6 + IL-7 dependent cells to differentiate into the subsequent IL-7 dependent stage. Likewise, when mu-chain positive IL-7 dependent cells express a functional light-chain gene, their growth signal requirement changes into an IL-7 unreactive stage.

Animals