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Biomedical subjects

R Yoshida

Publications and source records attributed to R Yoshida.

At least 145 records · Page 8Linked to original sources
PubMed1991

Cloning and expression of a cDNA encoding mouse indoleamine 2,3-dioxygenase.

The depletion of an essential amino acid (aa), tryptophan, caused by interferon-gamma (IFN-gamma)-mediated induction of indoleamine 2,3-dioxygenase (IDO) in mouse allografted tumor cells, has been suggested as a reason for the allograft rejection. To elucidate the mechanism of this IDO induction, attempts were made to isolate cDNA clones encoding mouse IDO. In seven of 25 mouse cell lines, IDO was induced by IFN-gamma, and the highest IDO induction was observed in the case of rectal cancer (CMT-93) cells, which were further stimulated two- to threefold by the simultaneous addition of dibutyryl cyclic AMP (Bt2cAMP). A cDNA library was prepared from poly(A)+ RNA isolated from CMT-93 cells treated with IFN-gamma/Bt2cAMP. The cDNA clones were isolated using the cDNA encoding human IDO as a probe. The mouse IDO cDNA encodes a 407-aa protein with an Mr of 45,639. The deduced aa sequence agreed with partial aa sequences derived from endopeptidase digestion of purified mouse IDO and revealed 61% homology with that of human IDO. Transient expression of the mouse IDO cDNA in COS-7 cells yielded a high level of IDO activity in the cells. Northern hybridization analysis of RNA in CMT-93 cells indicated that IFN-gamma induced the IDO mRNA, and that the level of RNA was increased by simultaneous addition of Bt2cAMP, while Bt2cAMP itself had no effect on mRNA induction.

Amino Acid Sequence↗
PubMed1991

Mononuclear phagocytes: a major population of effector cells responsible for rejection of allografted tumor cells in mice.

To understand the in situ mechanism of immunological response of recipient animals to allografted tumor cells, the types of cells that infiltrated into the rejection site were examined. When Meth A cells (H-2d) were given i.p. to an allogeneic [C57BL/6 (H-2b)] strain of mouse, the tumor cells ceased to grow on the 6th day, accompanied by an i.p. infiltration of leukocytes. The tumor cells were totally eliminated from the peritoneal cavity around the 12th day. The highest cytotoxic activity against Meth A cells was obtained with the peritoneal exudate cells harvested on day 8. On this day, the exudate cells consisted of three populations when examined by flow cytometry, and each was isolated by sorting. Each of them appeared to be homogeneous, and they were morphologically identified as lymphocytes; granulocytes; and medium-sized, mononuclear, less-granular cells. The cytotoxic activity was confined exclusively to the last population. The effector cells (H-2b) were cytotoxic against not only Meth A cells (H-2d) but also concanavalin A-stimulated allogeneic spleen cells [C3H/He (H-2k), CBA/N (H-2k), A/J (H-2a), BALB/c (H-2d), and DBA/2 (H-2d) strains of mouse]. The effector cells were totally inert against concanavalin A-activated syngeneic spleen cells [C57BL/6 (H-2b) and C57BL/10 (H-2b) strains of mouse]. The effector cells were phenotypically (Thy-1.2- CD3- Lyt-1- Lyt-2- L3T4- immunoglobulin- asialo GM1-), morphologically, and functionally distinct from cytotoxic T cells, natural killer cells, and lymphokine-activated killer cells but were adherent mononuclear phagocytes.

Animals↗
PubMed1991

Induction of indoleamine 2,3-dioxygenase in tumor cells transplanted into allogeneic mouse: interferon-gamma is the inducer.

Tryptophan depletion observed during induction of indoleamine 2,3-dioxygenase (IDO) in cultured cells has been suggested to involve a mechanism identical to that employed in self-defense against inhaled microorganisms and tumor growth. We recently reported that a dramatic induction of IDO occurred in i.p. transplanted tumor (Meth-A) cells undergoing rejection from allogeneic mice (C57BL/6), and that soluble factor(s) released from infiltrated host cells was responsible for the IDO induction. Here we report on the characterization of the soluble factor. To assay the factor, we used a 35 mm special culture dish (Transwell), which consisted of two wells divided vertically with a membrane (0.4 micron pore). Host cells (mainly lymphocytes) that infiltrated into the transplantation loci were cultured in the upper well, and untreated Meth-A cells in the lower well. With this in vitro system, the membrane-permeable factor, released by the host cells (upper well), induced IDO in the tumor cells (lower well). The culture superna tants, obtained by centrifuging the culture media from the upper and lower wells, contained the IDO inducer. The inducer activity was completely neutralized by the addition of antibody against interferon-gamma (IFN-gamma) but not by antibody against IFN-alpha/beta. The concentration of IFN-gamma in the medium after 1-day culture with a Transwell culture dish was found to be 2-3 U/ml based on the neutralization curve with the antibody. At this concentration, recombinant IFN-gamma induced IDO in Meth-A cells to the same extent as the inducer in the culture medium. These observations indicate that the in vivo factor for IDO induction in the allografted tumor cells is IFN-gamma.

Animals↗
PubMed1991

C3 deposition in IgA nephropathy in children and adolescents.

The aim of this study was to assess the significance of C3 deposition in IgA nephropathy in children and adolescents. One hundred and two patients aged 5-21 years (57 male and 45 female) were studied. The findings of C3 deposition were classified into 8 groups by immunofluorescent (IF) pattern and intensity as follows: group MC3+ (N = 12): mesangiocapillary pattern and 3+ in intensity; group MC2+ (N = 13): mesangiocapillary and 2+; group MC1+ (N = 4): mesangiocapillary and 1+; group M3+ (N = 11): mesangial and 3+; group M2+ (N = 24): mesangial and 2+; group M1+ (N = 18): mesangial 1+; group S (N = 12): only segmentally positive; and group N (N = 8): negative. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration, and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, fibrous crescents, adhesion and tubulo-interstitial change). IF findings were scored semiquantitatively and laboratory findings were also studied. The following results were obtained: 1) The scores of total activity index in MC groups were higher than in the M, S or N groups, and the greater the degree of C3 deposition, the higher the score; 2) Such result was not evident in the chronicity index; 3) High IF scores of IgG and IgM were found in the MC3+ and MC2+ groups; 4) Hematuria was more severe in MC3+ and MC2+ than in other groups, and proteinuria was more prominent in the MC than other groups. Thus the degree of C3 deposition was parallel with histological activity and urinary findings.

Adolescent↗
PubMed1991

C3 deposition in serially biopsied children with IgA nephropathy.

Twenty-five children with IgA nephropathy were studied by serial renal biopsy to investigate C3 deposition. The children were classified into three groups according to the immunofluorescent (IF) course of C3 deposition: group I (N = 9): unchanged or slightly decreased; group II (N = 4): changed to segmental deposition; and group III (N = 12): changed to negative deposition. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, adhesion, fibrous crescents and tubulo-interstitial change). The IF findings were scored semiquantitatively and laboratory data were also studied. The following results were obtained: 1. Normal urinalysis was often observed in group III; 2. The IF scores of IgA and IgG were decreased at the second biopsy in all groups, most notably in group III; 3. The activity indices at second biopsies were decreased in all groups, most notably in groups II and III, consistently with our previous study which showed that C3 deposition increases in accordance with histological activity; 4. The chronicity index was unchanged in all groups and C3 deposition did not reflect histological chronicity. Thus, this study indicates that C3 deposition occurs as the disease progresses and reflects histological activity.

Adolescent↗
PubMed1991

Surface-modulated skin layers of thermal responsive hydrogels as on-off switches: I. Drug release.

Thermosensitive co-polymers of isopropyl acrylamide (IPAAm) with butyl methacrylate (BMA) are capable of 'on-off' regulation of drug release in response to external temperature changes due to skin formation with increasing temperature. To clarify the role of the surface-modulated skin and controlled pulsatile drug release patterns, the surface shrinking process was regulated by changing the length of the methacrylate alkyl side-chain. Release of indomethacin in response to stepwise temperature changes between 20 and 30 degrees C from co-polymers of IPAAm with BMA, hexyl methacrylate (HMA), and lauryl methacrylate (LMA) was studied. The drug release rate during the 'on' state (20 degrees C) remained constant before and after the 'off' state (30 degrees C) when the period of the 'off' state was increased. These results suggest that the drug in the polymeric matrices diffused from the inside to the surface during the 'off' state even when no drug release was seen. The length of alkyl side-chain was found to be an important parameter in controlling the thickness and density of the surface skin layer.

Cross-Linking Reagents↗
PubMed1991

A rare case of infective aneurysm involving all three sinuses of Valsalva complicated by left single coronary artery.

Infective aneurysm showing dilatation of all three coronary sinuses of Valsalva due to infective endocarditis is extremely rare. We present the first report of such a case complicated by left single coronary artery. The patient was a 55-year-old man with a past history of untreated diabetes mellitus, cerebral infarction, aortic regurgitation and high-grade fever. He was admitted with a complaint of easy fatigability. In a treadmill exercise test, asymptomatic ischemic depression of the ST segment was observed. Two-dimensional echocardiography revealed marked dilatation of all three sinuses of Valsalva, and a mural thrombus within the dilated right sinus of Valsalva. On magnetic resonance imaging, an abnormal signal in the markedly dilated right sinus of Valsalva was revealed. Coronary arteriography showed left single coronary artery (L1 type by Sharbaugh's classification). The histopathological features of the affected aorta were thought to represent the healing stage of infective endocarditis. With regard to the myocardial ischemia in this patient, it was thought to have arisen mainly through aortic regurgitation and coronary atherosclerosis due to single coronary artery, and partly influenced by untreated diabetes mellitus.

Aneurysm, Infected↗
PubMed1991

Two cases of adult T-cell leukemia associated with acute pancreatitis due to hypercalcemia.

We report two cases of adult T-cell leukemia associated with acute pancreatitis and hypercalcemia. After sudden onset of epigastralgia, acute pancreatitis and hypercalcemia were found in both patients. There were no diseases that could explain the acute pancreatitis except for hypercalcemia probably due to adult T-cell leukemia. Thus we considered that hypercalcemia due to adult T-cell leukemia had led to acute pancreatitis. This is the first report of such a complication in adult T-cell leukemia.

Adult↗
PubMed1990

IFN-gamma is the inducer of indoleamine 2,3-dioxygenase in allografted tumor cells undergoing rejection.

The depletion of an essential amino acid, tryptophan, caused by induction of indoleamine 2,3-dioxygenase (IDO), has been shown to be a mechanism involving self-defense against inhaled microorganisms and tumor growth. We recently reported that the IDO is dramatically (approximately 50-fold) induced in allografted tumor (3-methylcholanthrene-induced ascites type tumor cells) cells undergoing rejection, and that the enzyme is induced by factor(s) released through the interaction of allografted tumor cells with infiltrating leukocytes. The culture supernatant of infiltrating leukocytes, which were harvested on day 7 after tumor transplantation, induced the highest IDO activity in the tumor cells. The inducer activity was completely neutralized by the addition of antibody to IFN-gamma but not by antibody to IFN-alpha/beta. Approximately 6 U/ml of IFN-gamma was detected by an ELISA assay in the 12-h culture supernatant with 2 x 10(6) leukocytes/ml, and rIFN-gamma at 6 U/ml induced IDO in 3-methylcholanthrene-induced ascites type tumor cells to the same extent as IFN-gamma in the culture supernatant. Moreover, i.p. administration of antibody to IFN-gamma almost completely inhibited the induction of IDO in the allografted tumor cells. These observations indicate that the factor responsible for IDO induction in the allografted tumor cells is IFN-gamma.

Animals↗
PubMed1990

Effects of bunazosin, a selective alpha 1-adrenergic blocking agent, on myocardial energy metabolism in ischemic dog heart.

Effects of a selective alpha 1-adrenergic blocking agent, bunazosin, on myocardial energy metabolism in the ischemic heart were studied. Ischemia was induced by ligating the left anterior descending coronary artery of the dog heart. Bunazosin was injected intravenously either 5 or 20 min before coronary artery ligation. Hearts were removed 3 min after coronary ligation and used for determination of the levels of cardiac tissue metabolites. Ischemia decreased the levels of ATP, creatine phosphate, glycogen and glucose, and increased the levels of ADP, AMP, hexose monophosphates and lactate. The energy charge potential (ECP) calculated was decreased by ischemia. Pretreatment with bunazosin inhibited the decrease in ATP and the increase in AMP caused by ischemia, resulting in the high value of ECP in the ischemic myocardium. Bunazosin also prevented the changes in carbohydrate metabolism caused by ischemia. It is concluded that bunazosin may reduce the influence of ischemia on the myocardium.

Adenine Nucleotides↗
PubMed1990

[Reproductive and developmental toxicity study of mofezolac (N-22) (1)--Study by oral administration of N-22 prior to and early stages of pregnancy in rats].

Mofezolac (N-22), a newly developed analgesic and anti-inflammatory agent, at dose levels of 0, 10, 30 and 90 mg/kg/day were administered orally to males from pre-mating to mating period and to females from pre-mating to early gestation period. Effects on reproductive performance of both sexes, especially reproductive capability, and development of offspring were examined. 1. In male parents, no changes in body weight and food consumption were found in all male groups, but the increase in gastric mucosal lesions such as ulcers were observed in 30 and 90 mg/kg/day groups. 2. In female parents, the decrease in body weight and food consumption of 90 mg/kg/day group during early gestation period were found, but at necropsy no changes were shown in all female groups. 3. Reproductive capability, mating and pregnancy performance were not affected. 4. No effects of N-22 on fetuses were observed. 5. The suggestions were as follows: No effect dose levels (NOELs) for male and female general-toxicologically were 10 and 30 mg/kg/day, respectively. NOELs for reproductive capability and for fetal development were 90 mg/kg/day.

Administration, Oral↗
PubMed1990

[Reproductive and developmental toxicity study of mofezolac (N-22) (4)--Study by oral administration of N-22 during the perinatal and lactation periods in rats].

peri- and postnatal study of mofezolac (N-22), a new developed analgesic and anti-inflammatory agent, was carried out with Wistar rats. N-22 at dose levels of 0, 25, 50 and 100 mg/kg/day were administered orally to pregnant and subsequent delivered dams from day 17 of gestation through day 21 of lactation. Body weight gains of dams treated with 50 and 100 mg/kg/day were depressed during perinatal period. Prolongation of pregnancy period, low performance of pup care with decrease in body weights and food consumptions were observed in 100 mg/kg/day group. Decrease in number and birth index, increase in number of stillborns and tendency to decrease in viability index on day 4 were found in 100 mg/kg/day group. Other parameters of development, behavior or reproductive capability of F1 animals showed no changes related to administration of N-22. It was suggested that no effect dose levels of N-22 were 25 mg/kg/day for dams viewpoint of general toxicity and that was 50 mg/kg/day for dams on reproductive performance and for offspring on development.

Administration, Oral↗
PubMed1990

[Antigenicity test of mofezolac (N-22)].

Antigenicity studies of mofezolac (N-22) were examined in mice and guinea pigs and the following results were obtained. The findings of active systemic anaphylaxis, passive hemagglutination test, 4 hour passive cutaneous anaphylaxis (4-hr PCA) and 8-day PCA in guinea pigs revealed that N-22 possessed neither immunogenic nor eliciting potentiality. However, N-22 was shown to be eliciting antigenicity in mice when given N-22-ovalbumin conjugate plus Freund's complete adjuvant (FCA) as immunogen.

Anaphylaxis↗
PubMed1990

[A clinical study of death in profound mental retardation with motor disturbance].

Among 848 cases of profound mental retardation with motor disturbance admitted to Metropolitan Medical Center of Severely Handicapped in the last 20 years, 98 died. The 94 cases whose cause of death was determined were clinically investigated. There was no difference in sex, and 72% of the patients died before the age of 15 years. Half of the patients died of pneumonia; sudden death occurred in 9, and ileus in 8. These three were thought to be the most important and characteristic causes of death in severely handicapped patients. In recent years, deaths due to pneumonia have decreased and those due to ileus have disappeared, but deaths due to malignant neoplasm have begun to be recognized. There were also some deaths from intracranial hemorrhage in young children, and some deaths from tracheal bleeding in those who had tracheal tubes. These two were also important causes of death in the patients. Sudden death had certain characteristics: most cases were adolescent or young patients with mixed quadriplegia who were sensitive to environmental changes and often showed marked hypertonia by athetosis, and in addition, all of their acute changes occurred between 5 and 8 a.m. or between 6 and 9 p.m.

Adolescent↗