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Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 505 records · Page 28Linked to original sources

[Primary Waldenström's macroglobulinemia associated with pure red cell aplasia in which Ts/c lymphocytes inhibiting erythroid precursors were detected].

Waldenström's macroglobulinemia (WMG) is a malignancy of B lymphocytes manifesting heavy accumulation of monoclonal IgM in the plasma. In about 80% cases of WMG, Normocytic normochronic anemia (NNA) is complicated. A case of WMG complicated with pure red cell aplasia (PRCA) and the results of in vitro CFU-E colony assay of bone marrow mononuclear cells (BMMNC) cultured with the patient's serum and/or peripheral lymphocytes were described. A 59-year-old male was admitted with serum total protein Level of 9.7g/dl and 48.2% of gamma globulin. The diagnosis of WMG was made by monoclonal IgM in immunoelectrophoresis. Severe NNA was initially demonstrated on admission and gradually deteriorated further. Both reticulocytes in peripheral blood and erythroid precursors in bone marrow were markedly decreased. Erythropoietin showed high values in plasma. Complication by PRCA was considered to be present in vitro study of a CFU-E colony formation of BMMNC from a normal volunteer showed significant suppression on addition of the patient's peripheral lymphocytes and adverse enhancement by adding the patient's serum. This inhibition of CFU-E colony formation was most prominent by the addition of suppressor/cytotoxic T lymphocytes (Ts/c) and was dose dependent. This result showed the existence of inhibitory Ts/c against proliferation of allogeneic erythroid precursors.

Erythroid Precursor Cells↗

[Detection of point mutation of K-ras gene codon 12 in biliary tract and ampullary carcinoma by modified two-step polymerase chain reaction].

The point mutation of K-ras gene at codon 12 was investigated in 11 cases of gall bladder carcinoma, 10 cases of extrahepatic bile duct carcinoma, 2 cases of intrahepatic bile duct carcinoma, and 4 cases of ampullary carcinoma by modified two-step polymerase chain reaction which employed paraffin embedded materials. The results revealed that there were point mutations in 6/11, 10/10, 2/2, and 4/4, respectively. Judging from the ratio of density of wild and mutant band, not all cancer cells in the tissue section contained the mutation. So it was suggested that the normal cells were initiated for the malignant transformation by ras gene mutations and then, selection might occur against cells containing ras mutations during progression of the tumor. Modified two-step polymerase chain reaction was markedly useful for detecting mutation even at low frequency among tumor cells.

Aged↗

Novel function of C4a anaphylatoxin. Release from monocytes of protein which inhibits monocyte chemotaxis.

The complement C4-derived anaphylatoxin, C4a, possesses a strong chemotaxis inhibitory capacity to blood monocytes at concentrations as low as 10(-16) mol/L. In our study, treatment with carboxypeptidase B to convert it to C4a des Arg77 decreased the inhibitory activity to less than 1/1,000. The extraordinary inhibitory capacity of C4a suggests the presence of an amplification mechanism in this inhibition. Indeed, we found that the conditioned media of peripheral blood mononuclear cells or monocyte/macrophage lineage cell lines (U937 and THP-1 cells) preincubated with 10(-16) mol/L C4a for 5 minutes or more at 37 C possessed the inhibitory capacity 100,000-fold stronger than the original activity of C4a. The monocyte-derived chemotaxis inhibitory factor seemed monocyte-specific. This cell-derived factor was sensitive to treatment with trypsin and chymotrypsin and immunologically distinct from C4a. The apparent molecular size of the monocyte factor was estimated to be approximately 20 kd by gel filtration. These results indicate that C4a anaphylatoxin induces the release from monocytes of a protein with inhibitory activity for monocyte chemotaxis.

Cell Line↗

[SN-FORTH/MSX: a state notation system for controlling behavioral experiments with a low-priced computer].

A software system, SN-FORTH/MSX, has been developed to control behavioral experiments with a low-priced personal computer, MSX. Designed on the model of state notation, SN-FORTH/MSX enables researchers to program easily a wide variety of behavioral procedures including complex processes that are hard to describe with conventional programming languages such as BASIC and C. Since the real-time monitor of this system has a capability of parallel processing of multiple state-sets, several independent experiments can be simultaneously conducted with a single computer. Users can observe and modify the working of real-time monitor in each instant with a set of run-time commands supplied in the system.

Behavior↗

Enhanced monoamine release in the median preoptic area following reduced extracellular fluid volume in rats.

The role of monoaminergic neural inputs to fluid regulatory systems in the median preoptic nucleus (MnPO) was investigated by examination of monoamine metabolism during reduction of systemic extracellular fluid volume in freely moving rats. Extracellular fluid volume was decreased iso-osmotically by subcutaneous polyethylene glycol (PEG), and extracellular noradrenaline (NA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using intracerebral microdialysis techniques. PEG treatments significantly increased NA, DA and DOPAC release in the MnPO area. The results suggest that monoaminergic neural systems in the region of the MnPO are important in the control of extracellular fluid balance.

Animals↗

Mitochondrial tRNA(Ile) mutation in fatal cardiomyopathy.

A patient with mitochondrial encephalomyopathy who died from progressive intractable cardiac failure at the age of 18 is reported. At the age of 4, he presented with short stature, but multiorgan disorders including deafness, focal glomerulosclerosis, epilepsy and dilated cardiomyopathy appeared later in his clinical course. Laboratory tests showed hyperlactatemia and hyperpyruvatemia. Histopathological findings demonstrated mitochondrial myopathy with ragged red fibers and focal cytochrome C oxidase-deficient fibers in skeletal and cardiac muscles. The activity of cytochrome C oxidase was 30% less than the control level in skeletal muscle. Sequencing of the entire mitochondrial tRNA genome revealed a novel point mutation in the tRNA(Ile) region (nt 4269). This A-to-G substitution was found in none of the 30 controls by screening using mispairing PCR and Ssp I digestion methods, suggesting that this new mutation was pathogenic in our case.

Adolescent↗

Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy.

To establish useful predictors of the intrahepatic recurrence of hepatocellular carcinoma (HCC) after partial hepatectomy, retrospective analyses of clinical and pathologic factors were done in 112 of 206 patients treated by partial hepatectomy. The absence or presence of intrahepatic recurrence was confirmed by a follow-up study. Cancer-free survival rates after 1, 2, 3, and 5 years were 54.8%, 36.7%, 32.5%, and 25.6%, respectively. The significant factors affecting recurrence were tumor size, number of tumors, cancer cell infiltration of the fibrous capsule of the tumor, portal involvement, and stage of the tumor, but the grade of anaplasia according to Edmondson-Steiner's classification and the severity of associated liver cirrhosis did not show a correlation with the incidence of recurrence. According to Akaike's Information Criteria (AIC), tumor number is useful for predicting early prognosis, and capsular infiltration is a good indicator of long-term survival. However, portal involvement gives much prognostic information throughout the entire postoperative period.

Adult↗

Human uterine endometrial adenocarcinoma: characteristic acquirement of synthetic potentials for II3SO3-LacCer and ganglio series sulfoglycosphingolipids after transfer of the cancer cells to culture.

The acidic glycosphingolipid composition of human uterine endometrial adenocarcinoma was compared with those of normal uterine endometrium at the proliferative and the secretory phases. Upon chemical composition analysis, no significant transformation-associated change of these glycolipids was observed. However, when cancer cells from the patients with human uterine endometrial adenocarcinoma were transferred to culture, the composition of glycosphingolipids, particularly sulfoglycosphingolipids, was significantly altered after the 70th doubling time. I3SO3-GalCer, which was contained in the original tissues of uterine endometrial adenocarcinomas, disappeared completely from the cultured cells at the 70th doubling time, whereas II3SO3-LacCer and ganglio series sulfoglycosphingolipids, which were originally contained in a trace amount or not present at all in the cancer tissues, became the major components in the total acidic glycosphingolipids in the cultured cells. Also, among cell lines established from several gynecological cancers, which include uterine cervical squamous carcinoma, uterine endometrial adenocarcinoma, ovarian clear cell carcinoma, choriocarcinoma, uterine sarcoma, ovarian sarcoma, and vulvar melanoma, only those cells derived from uterine endometrial adenocarcinoma expressed II3SO3-LacCer and ganglio series sulfoglycosphingolipids and the synthetic activities of these sulfoglycolipids, indicating that uterine endometrial adenocarcinoma cells characteristically lose the sulfotransferase to GalCer and acquire the sulfotransferase to LacCer after being transferred to culture in vitro. Thus, the unique sulfoglycosphingolipids and sulfotransferase are useful markers for the characterization of uterine endometrial adenocarcinoma among human gynecological cancers.

Adenocarcinoma↗

Glycosphingolipids of various human ovarian tumors: a significantly high expression of I3SO3GalCer and Lewis antigen in mucinous cystadenocarcinoma.

Among several human ovarian tumors, which include mucinous cystadenocarcinoma, serous cystadenocarcinoma, and clear cell adenocarcinoma, the mucinous cystadenocarcinoma showed a unique glycosphingolipid composition. In particular, more than 90% of the acidic glycosphingolipids in the mucinous cystadenocarcinoma is comprised of sulfolipids, which are hardly detected in normal ovary and are contained in concentrations of less than 40% in the other type of ovarian tumors. By means of negative ion fast atom bombardment mass spectrometry and gas liquid chromatography, the major sulfolipid in mucinous cystadenocarcinoma is confirmed to be I3SO3-GalCer with N-cerebronoyl phytosphingosine, that which contrasts with I3SO3-GalCer with N-nonhydroxy fatty acyl sphingosine as the major molecular species in the other ovarian cancers. In mucinous cystadenocarcinoma, galactosylceramide is found in the relatively high concentration and is also composed of N-cerebronoyl phytosphingosine. In addition, the concentrations of glycolipids with Le(a) and Le(b) antigenicities are significantly higher in mucinous cystadenocarcinoma than those in normal ovary and the other ovarian tumors.

Chromatography, Thin Layer↗

Increased iron content in the putamen of patients with striatonigral degeneration.

We measured the total content of iron, copper, zinc and manganese in the putamen of four patients with striatonigral degeneration (SND) and age- and gender-matched normal controls. The iron content in the SND patients was five times greater than in the controls. Electron microscopic histochemistry revealed the iron reaction products in the pigments showing a triphasic pattern of coarse, electron-dense globules, fine granular and fibrillary materials, and lamellated structures. These findings suggest that increased iron deposition may be related to pigment formation in the putamen of SND.

Aged↗

Enhanced stability of YEp plasmids in lager brewing yeasts is related to lager brewing yeast 2-microns DNA.

YEp plasmid stability in the presence of either Saccharomyces cerevisiae laboratory strain 2-microns DNA, or lager brewing yeast 2-microns DNA in the same genetic background, was compared under non-selective culture conditions. It was found that YEp plasmids were more stably maintained in the presence of lager 2-microns DNA under these conditions. By construction of laboratory-lager 2-microns DNA hybrid plasmids, an 867 bp StuI fragment of lager 2-microns DNA was shown to be responsible for the enhanced stability of the YEp plasmid. Nucleotide substitutions at two sites were found by sequencing this region. It was also confirmed that increasing cell ploidy enhanced YEp stability under non-selective conditions.

DNA, Fungal↗

Beta-carotene and/or vitamin E as modulators of alkylating agents in SCC-25 human squamous carcinoma cells.

Dietary levels of beta-carotene and vitamin E have been associated with cancer prevention and to a lesser extent, with therapeutic enhancement of cancer treatment. We report on the cytotoxicity of beta-carotene, vitamin E, and the combination of beta-carotene and vitamin E in human SCC-25 squamous carcinoma cells under various environmental conditions found in solid tumor masses. Beta-Carotene was selectively cytotoxic toward normally oxygenated cells and was generally more cytotoxic at normal pH than at acidic pH (6.45). Vitamin E was selectively cytotoxic toward normally oxygenated cells following 6 h exposure at normal pH and was generally equally cytotoxic toward normally oxygenated and hypoxic cells under the other conditions tested. Beta-Carotene was an effective modulator of cisplatin (CDDP) cytotoxicity toward SCC-25 cells, whereas vitamin E was not. Both beta-carotene and vitamin E were effective modulators of melphalan cytotoxicity toward SCC-25 cells. Treatment of SCC-25 cells with beta-carotene (70 microM, 2h) resulted in a reduction in superoxide dismutase activity, in glutathione-S-transferase activity, and in nonprotein sulfhydryl levels in the cells. Exposure to vitamin E or to a combination of beta-carotene and vitamin E increased the glutathione-S-transferase activity in SCC-25 cells by 40%-45% over the control value. Treatment with beta-carotene, vitamin E, or canthaxanthin reduced the incorporation of [3H]-thymidine into SCC-25 cells but not that into normal human keratinocytes. The most marked reduction in [3H]-thymidine incorporation into SCC-25 cells occurred following treatment with the combination of beta-carotene and melphalan. We hope to continue to explore the mechanisms of this effect and to study these combinations in vivo.

Alkylating Agents↗

Successful second allogeneic bone marrow transplantation in a relapsed acute myeloid leukemia patient with fungal liver abscess.

Disseminated fungal infection not infrequently complicates the course of allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised patients, and the prognosis of BMT patients who develop systemic fungal infection is very poor. We describe a patient who developed disseminated Candida albicans infection with liver abscess after the first allo BMT for acute myelogenous leukemia (FAB M2). The infection was successfully eradicated by the administration of miconazole and amphotericin B. However, 1 year after the first allo BMT, the patient suffered a relapse of acute myelogenous leukemia with fungal liver abscess. A second allo BMT, accelerating granulocyte recovery by recombinant human granulocyte colony-stimulating factor (rhG-CSF), was successfully performed and the fungal liver abscess resolved with a combination therapy of fluconazole and amphotericin B. The patient is alive and free of both leukemia and fungal disease more than 37 months after the first allo BMT and 25 months after the second allo BMT.

Adult↗

Effect of anticancer agents on cell cycle of regenerating hepatocytes in rats.

The effect of three anticancer agents, cisplatin, doxorubicin, and mitomycin, on liver regeneration after 70% partial hepatectomy in rats was investigated by total DNA content of the liver and flow cytometric analysis of hepatocyte nuclei using two-color staining of anti-bromodeoxyuridine monoclonal antibody and propidium iodide. Total DNA content of regenerating liver 7 days after hepatectomy showed significant suppression of regeneration by these agents (P less than 0.01). The inhibitory effects of the agents on the cell cycle of hepatocytes by flow cytometric analysis were (1) a delay of the peak or a decrease in the proportion of S phase nuclei and/or (2) polyploidization of the nuclei, demonstrated by accumulation of 8c and occasionally 16c nuclei, of which the DNA contents were four and eight times as much as that of diploid (2c) cell nuclei, respectively. The former (1) suggests G0 or G1 phase block, and the latter (2) G2 phase block. In terms of total DNA content of regenerating liver, the inhibitory effect was most prominent in the cisplatin-administered groups. The polyploidization of nuclei was most remarkable in the mitomycin-administered groups. Although the total DNA content recovered to the level of control at 6 weeks after hepatectomy, the polyploidization effect persisted in the drug-administered groups. These agents had no cytocidal action on proliferating hepatocytes as can be seen from the aspartate aminotransferase and alanine aminotransferase serum levels. We conclude that in a short-term observation, the anti-cancer agents significantly inhibit liver regeneration, although the inhibitory effect on DNA synthesis does not last long.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of PGE2 on interleukin-1 and superoxide release from primary-cultured human hepatic macrophages.

In order to learn more about how human hepatic macrophages function, we analyzed the effect of exogenous PGE2 on the amounts of interleukin-1 (IL-1) and superoxide (O2-) released from primary-cultured human hepatic macrophages (HHM phi). When endogenous PGE2 production was blocked by indomethacin, exogenous PGE2 reduced IL-1 release from HHM phi in a dose-dependent manner, whereas it tended to increase O2- release from HHM phi. These results may suggest the probable contribution of PGE2 in regulating HHM phi mediator release in vivo.

Cells, Cultured↗

Mitochondrial encephalomyopathies with the mutation of the mitochondrial tRNA(Leu(UUR)) gene.

Four families with mitochondrial encephalomyopathy are described. Probands of three families had typical clinical presentations of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), but the proband of family 4 lacked strokelike episodes. The mitochondrial DNA mutation of tRNA(Leu(UUR)) (transfer ribonucleic acid specific to leucine (UUR codon)) found in MELAS was examined in muscle DNA obtained from biopsy samples of the probands of four families and the maternal relatives of family 2. The mutation was detected in all muscle samples, and the degree of the mutated DNA was 68% to 84% by Southern blot analysis. However, the clinical patterns of the maternal relatives of family 2 were mild and distinctly different from MELAS. The same mutation was also detected in blood-derived DNA samples of all family members examined, including healthy mothers but not fathers, although the degree of mutation did not correlate with the clinical severity. These results confirmed the maternal inheritance of this disease and suggested that the mitochondrial DNA mutation (tRNA(Leu(UUR))) may cause clinical symptoms other than MELAS. The clinical findings of mitochondrial encephalomyopathy should be reinvestigated in terms of the mitochondrial gene mutation; the polymerase chain reaction method will be useful for screening for this mutation of mitochondrial DNA in blood samples.

Acidosis, Lactic↗