Search PubMed⌕ Search

Biomedical subjects

T Sumi

Publications and source records attributed to T Sumi.

At least 55 records · Page 3Linked to original sources

Anemia-inducing substance is related to elimination of lipolytic hyperactivity by cyclic plasma perfusion in human cancer cachexia.

We previously reported that cyclic plasma perfusion suppressed lipolytic activity in malignant tumor-bearing animals and reversed their body weight loss. In this study we investigated the relation between this phenomenon and interleukin (IL)-1 alpha, IL-1 beta, IL-6, interferon-gamma, leukemia inhibitory factor, tumor necrosis factor-alpha, and anemia-inducing substance (AIS) in vitro by examining changes in their levels in the plasma of advanced ovarian cancer patients. When the patients' plasma was incubated with noncoated charcoal for one hour, its lipolytic activity decreased by 39.0 +/- 2.4%, which was similar to the results obtained with the plasma of healthy subjects. IL-1 alpha, IL-1 beta, interferon-gamma, leukemia inhibitory factor, and tumor necrosis factor-alpha did not adsorb the charcoal. IL-6 was 3.7% adsorbed, but this did not cause a significant difference (p = 0.131). Nor was the recombinant form of these cytokines adsorbed to the charcoal. AIS, however, was 98.1% adsorbed. These results indicate that AIS is strongly associated with the reduction in lipolytic activity by cyclic plasma perfusion through noncoated charcoal resin.

Adult↗

The arcuate eminence is not a protrusion of the superior semi-circular canal but a trace of sulcus on the temporal lobe.

Thirteen cadavers (26 temporal bones) were examined to show the arcuate eminence, especially its correspondence to the superior semicircular canal and inferior surface of the temporal lobe. Arc-like eminences on the petrous bone were observed in 92 per cent of specimens, however, they did not exactly correspond to the superior semi-circular canal. Some eminences corresponded to sulci of the temporal lobe of which most were traces of the occipitotemporal sulcus. On the other hand, a dull, smooth and even domed eminence existed in nine temporal bones independently of the arc-like eminence. Those eminences corresponded to each superior semi-circular canal in only three out of nine specimens. The arcuate eminence was listed as an important landmark in the middle cranial fossa approach. However, in order to drill out the internal auditory canal safety, surgeons should rely on other landmarks or apply other methods from our data.

Humans↗

Complete amino acid sequences of three proteinase inhibitors from white sword bean (Canavalia gladiata).

Three major serine proteinase inhibitors (SBI-1, -2, and -3) were purified from the seeds of white sword bean (Canavalia gladiata) by FPLC and reversed-phase HPLC. The sequences of these inhibitors were established by automatic Edman degradation and TOF-mass spectrometry. SBI-1, -2, and -3 consisted of 72, 73, and 75 amino acid residues, with molecular masses of 7806.5, 7919.8, and 8163.4, respectively. The sequences of SBI-1 and -2 coincided with those of CLT I and II [Terada et al. (1994) Biosci. Biotech. Biochem., 58, 376-379] except only N- or C-terminal amino acid residues. Analysis of the amino acid sequences showed that the active sites of the inhibitors contained a Lys21-Ser22 against trypsin and Leu48-Ser49 against chymotrypsin, respectively. Further, it became apparent that about seven disulfide bonds were present. These results suggest that sword bean inhibitors are members of the Bowman-Birk proteinase inhibitor family.

Amino Acid Sequence↗

[Two cases of recurrent gastric cancer for which combination chemotherapy with pirarubicin, cis-platinum and 5-fluorouracil were markedly effective].

In the treatment of 2 patients with recurrent gastric cancer who showed bone metastasis and lymph node recurrence, we administered 30 mg/body of pirarubicin (THP) on the first day of treatment, and 30 mg/body of cis-platinum (CDDP) and 500 mg/m2 of 5-fluorouracil (5-FU) for 3 days (FP therapy). Marked effects were achieved. Gastric cancer of Borrmann IV type was diagnosed in Case 1, and total gastrectomy was performed. The histological type was poorly differentiated adenocarcinoma, and the histological classification was II. A bone metastasis was found three years after operation. The patient was CR after three courses of treatment, and has survived for 2 years. In Case 2, advanced gastric cancer was treated with neoadjuvant chemotherapy and distal gastrectomy. The histological type was moderately differentiated adenocarcinoma, and the histological classification was IIIa. Obstructive jaundice due to lymph node recurrence developed 6 years after operation. Two courses of treatment were provided after PTCD, and PR was observed. The patient has survived for 3 months. Both patients exhibited mild side effects such as anemia and leukocytopenia, but no serious complications were observed. Although various dosage regimens of FP therapy have been investigated, there has been a certain limit to the response rate achieved by this therapy, and new protocols have been explored. We achieved marked effects in 2 patients by adding THP to FP therapy. These cases are reported here together with some discussion of cases reported in the literature.

Adenocarcinoma↗

[Analysis of the salvage synthesis within biosynthesis of nucleic acid route in colon cancer].

Orotate phosphoribosyl transferase (OPRT), thymidine phosphorylase (TP), uridine phosphorylase (UP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthetase (TS) are enzymes which analyze the salvage synthesis within the biosynthesis of the nucleic acid route of colon cancer. These enzymes were measured in carcinoma and normal tissue. OPRT was 0.065 +/- 0.041 nmol/min/mg protein, TP 4.04 +/- 2.81 nmol/min/mg protein, UP 1.79 +/- 1.19 nmol/min/mg protein, DPD 23.8 +/- 12.0 pmol/min/mg protein, and TS 6.1 +/- 4.4 pmol/g tissue in the normal tissue, and OPRT was 0.199 +/- 0.146 nmol/min/mg protein, TP 13.63 +/- 6.04 nmol/min/mg protein, UP 5.84 +/- 2.37 nmol/min/mg protein, DPD 22.0 +/- 13.4 pmol/min/mg protein, TS 16.9 +/- 7.8 pmol/g tissue in the carcinoma. OPRT, TP, and UP in the carcinoma mainly existed about 3.06-3.37 times that in normal tissue and TS at about 2.77 times. No significant difference was seen in DPD. A correlation was found between OPRT in normal tissue and carcinoma. Biosynthesis of nucleic acid via salvage synthesis is actively stimulated. Enzymatic activity related to uracil was high, and was thought to be closely connected to the growth of the cancer.

Aged↗

Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2.

The rapid turnover of actin filaments and the tertiary meshwork formation are regulated by a variety of actin-binding proteins. Protein phosphorylation of cofilin, an actin-binding protein that depolymerizes actin filaments, suppresses its function. Thus, cofilin is a terminal effector of signaling cascades that evokes actin cytoskeletal rearrangement. When wild-type LIMK2 and kinase-dead LIMK2 (LIMK2/KD) were respectively expressed in cells, LIMK2, but not LIMK2/KD, phosphorylated cofilin and induced formation of stress fibers and focal complexes. LIMK2 activity toward cofilin phosphorylation was stimulated by coexpression of activated Rho and Cdc42, but not Rac. Importantly, expression of activated Rho and Cdc42, respectively, induced stress fibers and filopodia, whereas both Rho- induced stress fibers and Cdc42-induced filopodia were abrogated by the coexpression of LIMK2/KD. In contrast, the coexpression of LIMK2/KD with the activated Rac did not affect Rac-induced lamellipodia formation. These results indicate that LIMK2 plays a crucial role both in Rho- and Cdc42-induced actin cytoskeletal reorganization, at least in part by inhibiting the functions of cofilin. Together with recent findings that LIMK1 participates in Rac-induced lamellipodia formation, LIMK1 and LIMK2 function under control of distinct Rho subfamily GTPases and are essential regulators in the Rho subfamilies-induced actin cytoskeletal reorganization.

Actin Depolymerizing Factors↗

Quantitative anhydrous mercaptolysis of algal galactans followed by HPLC of component sugars.

This paper describes a new HPLC method for the sugar analysis of algal galactans containing 3,6-anhydrogalactose, which is readily destroyed during usual acid hydrolysis and methanolysis. By anhydrous mercaptolysis of galactans at 60 degreesC for 6 h with the newly developed solvent system, 0.5 N HCl/[ethanethiol:methanol (2:1, v/v)], component sugars, including 3,6-anhydrogalactose, were liberated quantitatively as their diethyl dithioacetals. The resultant sugar diethyl dithioacetals were found to have strong UV-absorption (absorption maximum of 3,6-anhydrogalactose diethyl dithioacetal in water, 191-192 nm; molar extinction coefficient, 4,400). The sugar diethyl dithioacetals were then resolved simultaneously within 15 min by reversed phase HPLC with 30% acetonitrile as the eluent and detected by UV-absorption at 215 nm. Amounts of sugar diethyl dithioacetals less than 50 pmol can be determined without further derivatization.

Absorption↗

Metabolic and morphologic characteristics of adipose tissue associated with the growth of malignant tumors.

Changes in total body fat and the metabolic and morphologic characteristics of adipose tissue were sequentially investigated in individual rabbits implanted with VX2 tumors to elucidate the pathology of the fat reduction in animals with malignant tumors as compared with that of diet-restricted rabbits. Lipogenesis in normal, VX2-implanted, and diet-restricted rabbit groups on day 40 after the start of the experiments was 19.1 +/- 2.9, 13.3 +/- 3.5, and 41.7 +/- 6.0 x 10(5) cpm/g/h, respectively, and glycerol liberation by their adipose tissue was 199 +/- 21, 528 +/- 94, and 301 +/- 45 nmol/g/h, respectively. In addition, apoptotic cells were noted in the adipose tissue of VX2-implanted rabbits on days 20-30 after implantation, but not in diet-restricted rabbits. The results showed clear differences between the total body fat reduction profiles of VX2-implanted rabbits and diet-restricted rabbits, suggesting a characteristic lipid metabolism with enhanced lipolysis and diminished lipogenesis in VX2-implanted rabbits. The results strongly suggest that adipocyte apoptosis might be involved in these phenomena.

Adipose Tissue↗

Lipolytic activity of anemia-inducing substance from tumor-bearing rabbits.

Anemia-inducing substance (AIS) is a protein of approximately 50,000 molecular weight secreted by malignant tumor tissue that depresses erythrocyte and immuno-competent cell functions; in this study, its biological effects on adipocytes were examined. Changes in body weight, total body fat, and food intake were investigated in rabbits after VX2 carcinoma transplantation, and the results showed reductions of 11%, 24%, and 30%, respectively, at 40 days after transplantation compared with baseline values (before transplantation). The values were even more markedly reduced 70 days after transplantation. When cyclic plasma perfusion (2 times/wk) was started at 40 days after transplantation, the values at 70 days after transplantation (30 days after beginning plasma perfusion) recovered to 91%, 84%, and 87%, respectively, of the baseline values. AIS fractions were isolated from rabbit plasma by using a phenyl-Sepharose column before transplantation, 40 and 70 days after transplantation, and 30 days after start of plasma perfusion, and AIS activity and lipolytic activity were measured. The results showed enhancement of AIS activity and lipolytic activity as the tumors grew. Lipolytic activity also returned to baseline value as AIS was removed by adsorption by plasma perfusion, and there was a high correlation between lipolytic activity and AIS kinetics. These results strongly suggest that AIS might be one of the substances involved in the enhanced lipolytic activity in advanced tumor-bearing subjects.

Adipose Tissue↗

Elimination of anemia-inducing substance by cyclic plasma perfusion of tumor-bearing rabbits.

We carried out a fundamental study to search for a therapeutic modality that would remove the anemia-inducing substance (AIS) from the plasma of cancer patients because it is thought to be one of the substances responsible for anemia and immunodeficiency in advanced cancer patients. Using AIS isolated from the plasma of patients with advanced ovarian carcinoma, we confirmed that adsorption of AIS to noncoated charcoal was nonspecific and high. Moreover, it was verified that VX2 carcinoma-bearing rabbits are an optimal experimental model for plasma perfusion. The data obtained on day 40 after transplantation (hemoglobin, 9.1+/-2.1 g/dl; osmotic pressure inducing RBC lysis, 137+/-11 mosmol/kg; lymphocyte stimulation index, 8.8+/-8.6; and RBC fragility-inducing activity, 40+/-9 mosmol/kg) proved similar to the hematological findings in patients with cancer cachexia. A 1-h plasma perfusion (3 ml/min) through noncoated charcoal was performed in tumor-bearing rabbits, and it resulted in the restoration of RBC fragility-inducing activity and suppression of lymphocyte blast formation to pretransplantation values. When plasma perfusion was performed every 3 days, RBC fragility-inducing activity, which increased again 3 days after perfusion, was diminished, and RBC osmotic resistance was within the normal range from the fourth perfusion onward. These results showed that cyclic plasma perfusion is effective in sustained removal of RBC fragility-inducing factor from plasma, suggesting that it might have the potential for clinical application.

Adsorption↗

Muscle cell apoptosis is responsible for the body weight loss in tumor-bearing rabbits.

In order to elucidate the cause of body weight loss in the early stage of tumor progression, morphological changes of striated muscle were investigated in rabbits every 10 days after VX2 carcinoma implantation. The lean body mass started to decrease in the tumor-bearing rabbits 10 days after implantation, and body fat ratio showed a significant decrease from 30 days, different from the starved rabbits, whose lean body mass and body fat ratio started to decrease from 10 days. Morphological hallmarks of apoptosis in muscle cells were detected in tumor-bearing animals prior to the tumor growth but not in starved animals. These findings suggest that muscle cell apoptosis may be responsible for the body weight loss in the early tumor-bearing.

Animals↗

A gas chromatographic method for the sugar analysis of 3,6-anhydrogalactose-containing algal galactans.

This paper describes a new gas chromatographic method for the compositional analysis of algal galactans containing 3,6-anhydrogalactose, which is readily destroyed in usual acid hydrolysis and methanolysis. Mercaptolysis of galactans was carried out under an anhydrous condition using the newly developed solvent system, an ethanethiolic HCl solution which had been prepared by blowing dry HCl gas into ethanethiol. By heating galactans in 0.5 N HCl/ethanethiol at 60 degrees C for 12 h, component sugars including 3,6-anhydrogalactose were released quantitatively as their diethyl mercaptals. The monosaccharide diethyl mercaptals were trimethylsilylated and analyzed by gas-liquid chromatography. Each component monosaccharide was detected as a single peak since neither anomeric nor structural isomers can be produced by mercaptolysis. Furthermore, the solvent system was improved by the addition of methanol in a ratio (2/1, v/v) of ethanethiol to methanol. Heating of galactans at 60 degrees C in 0.5 N HCl/[ethanethiol:methanol (2/1, v/v)] released more rapidly and quantitatively monosaccharide diethyl mercaptals without any formation of monosaccharide methyl glycosides. The present method was applicable to not only algal galactans but also algal powders.

Carbohydrate Sequence↗

Body composition analysis of cachectic rabbits by total body electrical conductivity.

A simple formula (1.536 x TOBEC + 475.146 = LBM, where TOBEC is total body electrical conductivity and LBM is lean body mass) to estimate LBM in grams was developed on the basis of the total body fat data obtained by ether extraction and TOBEC in normal rabbits. The formula was also applicable to rabbits with cachexia induced by inoculation of VX2 carcinoma or by starvation. We were able to assess the losses of body fat in the rabbits with cachexia at 10-day intervals by using TOBEC.

Animals↗

Thyroid hormone, all-trans retinoic acid, and 9-cis retinoic acid functioned as negative modulators of the effect of glucocorticoid on induction of alpha 1-acid glycoprotein mRNA in RLN-10 cells.

The expression of acute-phase protein genes is controlled by many factors, such as IL-1, IL-6, glucocorticoids, thyroid hormone (T3), and retinoic acids. We studied the interaction of T3, glucocorticoids, all-trans retinoic acid (RA), and 9-cis retinoic acid (9cRA) on the expression of the rat alpha 1-acid glycoprotein (AGP) gene in vitro. Dexamethasone (Dex) activated AGP gene expression in a rat liver derived cell line, RLN-10. Although T3, RA, and 9cRA by themselves had no effect on AGP production, they reduced the response to Dex of the AGP gene.

Alitretinoin↗

Transferrin and transferrin receptor in human hypophysis and pituitary adenomas.

Transferrin (Tf), a major transport protein for iron in the blood and an essential growth factor in some tissues, acts via specific transferrin receptor (TfR). We studied the cellular distribution of Tf and TfR gene expression in 50 human nontumorous autopsy pituitaries and 42 surgically removed pituitary adenomas. Tf and TfR mRNA accumulation was correlated with Ki-67 proliferation marker. In nontumorous pituitaries without iron deposits Tf immunoreactivity was localized in some growth hormone, prolactin, adrenocorticotropin, thyrotropin, and luteinizing hormone cells. Most adenohypophysial cells were immunopositive for TfR. In pituitaries with iron deposits, Tf and TfR were localized only in iron-free cells. Tf mRNA and protein were present in 27 and 32 adenomas, respectively; Ki-67 labeling index of tumors positive for Tf mRNA was significantly higher than in those without transcript (0.94% versus 0.51%; P < 0.025). A positive linear correlation between tumor growth fraction and Tf mRNA signal intensity was evident (r = 0.32; P = 0.04). TfR mRNA and encoded protein were demonstrated in 26 and 31 adenomas, respectively; Ki-67 immunoreactivities were not correlated with the presence of TfR transcripts and signal intensities. These data suggest that Tf may act as a growth-promoting factor for pituitary tumors.

Adenoma↗

Effects of plasmapheresis in a rabbit model of cancer cachexia.

We developed a model of cancer cachexia by transplanting VX2 tumors into rabbits and investigated the effects of plasmapheresis in this model. AIS activity was identified in supernatants obtained from VX2 tumor by phenyl Sepharose chromatography. Fractions eluted with 0.5 M NaCl showed the ability to damage the red blood cell membrane and suppress immunity. Rabbits exhibited marked weight loss, anemia and immunodeficiency 40 days after transplantation of VX2 tumors. Plasmapheresis inhibited plasma-induced damage of the red blood cell membrane and suppression of immunity. Twice-weekly plasmapheresis resulted in gradual normalization of cellular immunity. Weight loss and survival were also improved. No side effects were observed.

Animals↗

Molecular cloning of sheep and goat ferredoxin reductase messenger ribonucleic acids, and identification of an alternatively spliced form of sheep ferredoxin reductase.

Complementary DNA clones of mRNAs for sheep and goat NADPH-ferredoxin reductases (ferredoxin NADP+ oxidoreductase, EC 1.18.1.2) were isolated by the reverse transcriptase polymerase chain reaction method, and the complete nucleotide sequences of the coding and 3'-flanking regions of these cDNA clones were determined. Comparative analysis using the deduced amino acid sequences of NADPH-ferredoxin reductases clarified the interspecific conservation of the ferredoxin-binding and flavin adenine dinucleotide (FAD)-binding regions, confirming the results reported previously. During this study, we happened to identify an alternatively spliced mRNA that completely lacks exon 3, just adjacent to the FAD-binding region of the sheep NADPH-ferredoxin reductase cDNA clone. In the screening of other alternatively spliced mRNAs of NADPH-ferredoxin reductases derived from several steroidogenic organs, such as adrenocortices, testes, and ovaries of sheep and goats, only one kind of alternatively spliced mRNA as described above was detected in sheep adrenocortices. Then, we constructed Escherichia coli expression systems for these two forms of mRNA and analyzed their enzymatic properties. We found that the ability of the alternatively spliced NADPH-ferredoxin reductase protein to transfer electrons to ferredoxin is completely abolished because FAD binding is inhibited.

Alternative Splicing↗