Biomedical subjects

H Ueda

Publications and source records attributed to H Ueda.

At least 649 records · Page 36Linked to original sources

PubMed1991

[5-fluorouracil concentration in gastroenterological tumor tissues, in adjacent normal tissues, and in serum after preoperative oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR)].

The 5-fluorouracil (5-FU)-concentration in resected tumor tissues was compared with that in the adjacent normal tissues or that in serum. Twenty-three patients with cancer of the digestive organs [(carcinoma of the stomach (12), colon (6), gallbladder (1), liver (1), ampulla of Vater (1), bile duct (1) and pancreas (1)] were administered orally 600-1, 200 mg/day of 5'-deoxy-5-fluorouridine (5'-DFUR) for 3 to 5 consecutive preoperative days. The average 5-FU-concentration in tumor tissues of 14 patients with 16 specimens measured 5 hours after final administration of 5'-DFUR was 62 ng/g. This level was significantly higher than that in adjacent normal tissues (21 ng/g, p less than 0.01). With 10 out of these 14 patients, the 5-FU-concentration in the serum was also measured. Among these 10 patients, the concentration of 5-FU in tumors (54 ng/g) was significantly higher than in adjacent normal tissues (19 ng/g) and in serum (12 ng/ml). At 6 to 9 hours after final administration, the mean concentration of 5-FU was 33 ng/g (n = 4) in tumor tissues, 30 ng/g (n = 5) in adjacent normal tissues and 24 ng/ml in serum. There was no significant difference among these mean values. For 4 patients whose specimens were taken at 17 to 18 hours after the last 5-FU administration, the mean concentration of 5-FU was 29 ng/g (n = 4) in tumor tissues, 14 ng/g (n = 3) in adjacent normal tissues and 4 ng/ml (n = 2) in serum.

Administration, Oral↗

PubMed1991

[Thallium-201 lung uptake in patients with chronic phase of myocardial infarction].

To study pathophysiological significance of Tl-201 lung uptake in coronary artery disease Tl-201 lung uptake was studied in 159 patients with chronic phase of myocardial infarction. Tl-201 lung uptake images were collected after rest Tl-201 myocardial imaging. Tl-201 lung uptake was estimated by comparing maximal lung counts with maximal myocardial counts (thallium lung heart ratio: LHR). Good correlation between LHR and mean pulmonary artery wedge pressure (mPw) and between LHR and left ventricular ejection fraction (EF) were obtained, (mPw = 2.7 +/- 10.5 LHR r = 0.52 n = 102, p less than 0.001, EF = 84.9-52.2 LHR r = -0.61 n = 159, p less than 0.001). It was noted that Tl-201 did not accumulate uniformly through the lung field and usually maximal Tl-201 lung uptake was noted at the basal zone of the right lung. Tl-201 lung uptake in the upper zone of the right lung increased in proportion to the hemodynamic deterioration. Interesting differences were noted between Tl-201 lung uptake in patients with chronic phase of myocardial infarction and that in patients with acute phase of myocardial infarction. The prognosis and clinical status of patients with markedly increased Tl-201 lung uptake (LHR greater than 0.8) in chronic phase were more excellent than the patients with similar Tl-201 lung uptake in acute phase. Hemodynamic parameters in patients with markedly increased Tl-201 lung uptake (LHR greater than or equal to 0.8) in chronic phase were significantly better than in those in acute phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗

PubMed1991

A limitation of endoscopic ultrasound: an unusual case of early gastric cancer overlying a pancreatic rest.

Endoscopic ultrasonography (EUS) has been developed as a valuable tool for examining the depth of carcinoma invasion and evaluating the submucosal tumors of the gastrointestinal tract. In the present case, that of a 60-yr-old woman, the work-up of radiography and conventional endoscopy revealed an ulcerating cancer of the stomach. Subsequent EUS showed a solid high-echoic mass occupying the third (submucosal) and fourth (muscularis propria) layers of gastric wall, suggestive of an advanced cancer invading the muscularis propria. However, histologic examination of the surgical specimen showed that this tumor was early submucosal carcinoma confined to the surface of a pancreatic rest. Retrospective evaluation of EUS pictures proved that the mass had tubular or circular echoless structures associated with thickening of the fourth layer, suggesting the pancreatic rest. Our experience in reviewing EUS findings of this tumor seems noteworthy, inasmuch as EUS indicates that EUS may provide certain characteristic features of gastric pancreatic rest that should be differentiated from invading carcinoma.

Carcinoma↗

PubMed1990

Identification and purification of a Bombyx mori homologue of FTZ-F1.

Extracts from embryos and from posterior and middle silk glands of the silkworm, Bombyx mori contain a sequence specific DNA binding factor termed BmFTZ-F1. The factor binds to the recognition site of FTZ-F1, a positive regulator of the fushi tarazu gene in Drosophila melanogaster. BmFTZ-F1 and FTZ-F1 share the same methylation interference patterns, the same chromatographic behaviors and similar protease digestion profiles. Anti-FTZ-F1 cross reacts with BmFTZ-F1. These results indicate that BmFTZ-F1 is a B. mori homologue of FTZ-F1. The mobility of the factor-DNA complex formed in the silk gland extract changes depending on the developmental stages. Purification of BmFTZF1 to an almost homogeneous state reveals that the factor is a 73 kd protein.

Animals↗

PubMed1990

'Ischemic tolerance' phenomenon found in the brain.

We investigated the possibility that neuronal cells given a mild ischemic treatment sufficient to perturb the cellular metabolism acquired tolerance to a subsequent, and what would be lethal, ischemic stress in vivo. Cerebral ischemia was produced in the gerbils by occlusion of both common carotids for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. Minor 2-min ischemia in this model depletes high-energy phosphate compounds and perturbs the protein synthesis, but never causes neuronal necrosis, and therefore was chosen as mild ischemic treatment. Single 2-min ischemia 1 day or 2 days before 5 min ischemia exhibited only partial protective effects against delayed neuronal death. However, two 2-min ischemic treatments at 1 day intervals 2 days before 5 min ischemia exhibited drastically complete protection against neuronal death. The duration and intervals of ischemic treatment, enough to perturb cellular metabolism and cause protein synthesis, were needed respectively, because neither 1-min ischemia nor 2-min ischemia received twice at short intervals exhibited protective effects. This 'ischemic tolerance' phenomenon induced by ischemic stress--which is unquestionably important--and frequent stress in clinical medicine, is intriguing and may open a new approach to investigate the pathophysiology of ischemic neuronal damage.

Animals↗

PubMed1990

Medullary carcinoma with lymphocytic infiltration of the stomach. Clinicopathologic study of 27 cases and immunohistochemical analysis of the subpopulations of infiltrating lymphocytes in the tumor.

The current study attempts to clarify the possible immune response that occurs in medullary carcinoma with lymphocytic infiltration of the stomach by an immunohistochemical analysis of the subpopulations of tumor-infiltrating lymphocytes. This carcinoma was histologically characterized by the sparse population of small nests consisting of poorly differentiated carcinoma cells, widely separated by intervening nondesmoplastic stroma infiltrated uniformly with abundant lymphocytes frequently accompanied by lymph follicles. An immunohistochemical analysis revealed that T-cells were evenly distributed throughout the tumor with intimate contact with individual carcinoma cells, except the lymph follicles consisted mainly of B-cells. Because of the similarities of morphologic features and subpopulations of tumor-infiltrating lymphocytes of this carcinoma to the normal lymphoid tissue, an organized immune response combined with cell-mediated and humoral immunities against the invading carcinoma cells seemed to occur in this type of gastric carcinoma, resulting in a excellent prognosis compared with that in ordinary gastric carcinoma.

Adult↗

PubMed1990

Evidence for receptor-mediated inhibition of intrinsic activity of GTP-binding protein, Gi1 and Gi2, but not G0 in reconstitution experiments.

The receptor-mediated inhibition of intrinsic activities of GTP-binding proteins (G-proteins) was studied. Pertussis toxin (IAP)-substrate G-protein, Gi1, Gi2 or G0, was prelabeled with [alpha-32P]GDP and reconstituted with synaptic membranes of the guinea pig cerebellum in the presence of 0.02% of Chaps. Intrinsic activities of G-proteins were evaluated by the release of [alpha-32P]GDP in exchange for added GppNHp or GDP in reconstituted preparations. U-50,488H (1 nM-10 microM), a specific kappa-subtype of opioid receptor agonist, inhibited the [alpha-32P]GDP release in exchange for added 1 microM GppNHp in Gi1-reconstituted preparations in a concentration-dependent manner. On the other hand, the kappa-opioid agonist at 10 microM increases the Km values of GppNHp, but not GDP in exchange for [alpha-32P]GDP release in preparations reconstituted with Gi1 or Gi2, but not with G0. These findings indicate that kappa-opioid receptor is coupled to inhibition of intrinsic activities of Gi1 and Gi2, but not G0, in guinea pig cerebellar membranes. In addition, it was revealed that the mode of action is mediated by a decrease in affinity of GTP (or its analog) for G proteins, but not by a change in affinity of GDP.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1990

Phosphorylated mu-opioid receptor purified from rat brains lacks functional coupling with Gi1, a GTP-binding protein in reconstituted lipid vesicles.

The effects of phosphorylation of a mu-opioid receptor on signal transduction to G-protein were studied. The mu-opioid receptor purified from rat whole brains was reconstituted with purified Gi1 in phosphatidylcholine vesicles. DAGO, a mu-opioid agonist at 1 microM-1 mM increased GTPase activity by 10-110% of control, in a concentration-dependent manner. When the mu-opioid receptor was phosphorylated by cyclic AMP-dependent protein kinase prior to reconstitution with Gi1, the DAGO-stimulation was markedly reduced (20% increase at 1 mM DAGO).

Animals↗

PubMed1990

Kappa-opioid agonist inhibits phospholipase C, possibly via an inhibition of G-protein activity.

In synaptic membranes of guinea pig cerebellum, in which preparations U-50, 488H, a kappa-opioid agonist inhibits G-protein activity, the same kappa-agonist at 100 nM inhibited the phospholipase C (PLC) activity stimulated by 100 microM GTP in the presence of 10 microM Ca2+. The present study provides a unique hypothetical mechanism that the receptor-mediated inhibition of PLC is mediated by inhibition of G-protein activity.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1990

Purification of a novel type of calcium-activated neutral protease from rat brain. Possible involvement in production of the neuropeptide kyotorphin from calpastatin fragments.

We have found a novel type of Ca2(+)-activated neutral protease in rat brain cytosol which cleaves -Tyr-Arg-containing calpastatin fragments to release the neuropeptide kyotorphin. This enzyme was purified about 26,000-fold by column chromatography as follows: DE52 cellulose, Ultrogel AcA 44, thiopropyl-Sepharose 6B, second DE52 cellulose, Ultrogel AcA 34, and blue Sepharose CL-6B. The molecular mass of the enzyme was estimated to be 65-75 kDa by gel filtration. The purified enzyme gave a single band of 74 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Some properties of this enzyme were similar to those of the calpains, i.e. an absolute requirement for Ca2+, maximal activity at neutral pH, and inhibition by sulfhydryl reagents such as p-chloromercuriphenylsulfonic acid and N-ethylmaleimide. However, it differs from the calpains in that it possesses no caseinolytic activity, separates from the calpains on the first DE52 column, and is insensitive to leupeptin and E-64 (N-[N-(L-3-trans-carboxyoxrian-2-carbonyl)-L-leucyl]agmatine). Thus, the molecular mass, the substrate specificity, the chromatographic behavior, and the inhibitor spectrum all suggest that this enzyme is a novel type of Ca2(+)-activated neutral protease.

Amino Acid Sequence↗

PubMed1990

[Study on neoadjuvant chemotherapy of Borrmann 4 type carcinoma of stomach and its clinical significance].

Considering a high potential of biological malignancies of Borrmann 4 type carcinoma (abbr., Borr. 4) of the stomach, preoperative induction (neoadjuvant) chemotherapy was applied to patients with Borr. 4 as an initial therapy. Anticancer drugs used in this study were FAM-OK432, sequential MTX-5Fu or UFT-M through aortic infusion or induced hypertension chemotherapy (IHC) in order to obtain selective enhancement of drug delivery into tumor tissue. These trials were carried out on 24 patients who had Borr. 4 type carcinoma. The response to neoadjuvant chemotherapy showed CR in 1 case, PR in 3 cases and MR in 4 cases. The objective improvement except the primary gastric lesion showed shrinking of distant metastatic lymph nodes along paraaorta or Virchow of 50% (5/10), disappearance of pleural or peritoneal fluids 85. 7% (6/7) and marked decrease of tumor marker such as CEA, CA19-9 or CA125 100% (12/12). In one of 5 cases showing morphological improvement of primary gastric lesion, no viable cancer cells were seen in the stomach associated with multiple foci of granulofibromatous lesion of regional nodes. In 17 cases of 24 total gastrectomy was done with extended lymphadenectomy (R2-R3). While there was no difference in the median survival time (MST) among curable resection group, MST of non-curable resection group with neoadjuvant chemotherapy showed a fairly good prognosis for 14 months as compared to that of 4 months without chemotherapy. As for disease-free survival, patients whose tumor showed a high response to neoadjuvant chemotherapy had a good prognosis in non-curable resection group (p less than 0.01). In conclusion our results demonstrated that patients whose tumor were effectively destroyed by neoadjuvant chemotherapy against Borr. 4 carcinoma of stomach had an improved prognosis.

Adult↗

PubMed1990

Use of pedicled omental flap in treatment of empyema.

Omental pedicle flaps were used in the treatment of patients with acute and chronic empyema with bronchopleural fistula. In 5 patients (group 1) with postoperative acute empyema owing to bronchial stump fistula, an omental covering was applied as a reinforcement to close the fistula. Six patients in group 2 with chronic tuberculous or Aspergillus empyema with multiple fistulas initially underwent open-window thoracostomy or cavernostomy and secondarily had omental transposition. In all patients, the right gastroepiploic vessels were used to provide the blood supply for the flap. Successful closure of the bronchial stump was obtained in all patients in group 1, but 2 of them died of recurrence of their underlying lung carcinoma within 1 year. Five of the 7 patients in group 2 had a favorable outcome, but 2 patients had partial recurrence after omental plombage. From our experience with these patients, we believe that the omental flap is effective for closing fistulas due to postoperative or chronic empyema but has only limited success in patients whose lungs are severely damaged by persistent infection.

Adult↗

PubMed1990

Prominent stacking interaction with aromatic amino acid by N-quarternization of nucleic acid base: X-ray crystallographic characteristics and biological implications.

In order to investigate the mode of interaction between the N-quarternized cytosine base and the aromatic amino acid, the crystal structure of the 3-methyl-cytidine-5'-monophosphate:tryptamine complex was analyzed by X-ray diffraction. The complex crystals were stabilized by extensive hydrogen bond formations in which eight independent water molecules per complex pair participated. A prominent stacking interaction, characterized by a parallel alignment of both rings with a separation distance of ca. 3.4 A, was observed between the cytosine base and the indole ring. Combining the present results with X-ray crystallographic data on the adenine--and guanine--aromatic amino acid interactions, we summarize the structural characteristics observed in the stacking interaction of the N-quarternized nucleic acid base with the aromatic amino acid and discuss their biological implications, especially in connection with the significance of N-protonation of nucleic acid base for selective recognition by protein.

Adenine↗

PubMed1990

Chronic toxicity and carcinogenicity of methylmercury chloride in B6C3F1 mice.

A 2-year feeding study of methylmercury chloride (MMC: 0, 0.4, 2, or 10 ppm) was conducted in B6C3F1 mice (60 mice of each sex/group) to compare chronic toxicity and carcinogenicity results with those for ICR mice from our previous study in which males of the 10-ppm group showed an increased incidence of renal tumors without any abnormal in-life parameters. In B6C3F1 mice of the 10-ppm group, neurotoxic signs characterized by posterior paralysis were observed in 33 males after 59 weeks and in 3 females after 80 weeks. In males, a marked increase in mortality and a remarkable decrease in body weight gain were observed after 60 weeks. Toxic encephalopathy consisting of neuronal necrosis of the brain and toxic peripheral sensory neuropathy were induced in both sexes in this group. Chronic nephropathy, testicular atrophy, and glandular stomach ulcer increased in incidence in the males; chronic nephropathy also increased in incidence in females. In proliferative lesions, there were significant increases in the incidence of renal adenoma and/or carcinoma (16/60) and tubular cell hyperplasia (14/60) in males of the 10-ppm group, as compared to the control group. The incidence of chronic nephropathy also increased in males of the 2-ppm group. The results of this study indicate that the susceptibility of B6C3F1 mice to renal toxicity and renal carcinogenicity is comparable to that of ICR mice, and B6C3F1 mice are more sensitive to the chronic neurotoxic effects of MMC than are ICR mice.

Animals↗

PubMed1990

Differential effects of interleukin 2 receptor-targeted therapy on heart and kidney allografts in rats. Depression of effectiveness of ART-18 monoclonal antibody treatment by uremia.

ART-18, a mouse antirat IL-2R mAb inhibits IL-2 binding and IL-2-dependent T cell growth. Although both (LEW x BN)F1 kidney and heart allografts survive ca. 3 weeks in ART-18-treated LEW rats (acute rejection occurs within 10 days, P less than 0.001), the host responses against the two organs vary. In the heart model, the splenic CD4:CD8 ratio as determined by FMF was similar both in untreated and treated animals, but decreased significantly in kidney recipients conditioned with ART-18. In both mAb-modulated animal groups, splenocytes inhibited test MLR and prolonged test cardiac allograft survival in a donor-specific fashion upon adoptive transfer, suggesting that ART-18 mediates "sparing" of Ts. However, both CD4+ and CD8+ cells from kidney-grafted hosts conferred suppression in vivo; only the CD8+ subset was effective in the heart model. Immunohistologically, IL-2R+ cells were absent in the heart grafts of treated hosts; a significant proportion of the kidney cell infiltrate remained IL-2R+ despite continuous mAb administration. Although ART-18 therapy prolonged renal graft survival significantly, function was poor and the rats remained uremic. However, when one of the native kidneys was retained and the rat continued to enjoy normal renal function, IL-2R+ cells were abolished from the graft infiltrate, as shown by FMF and immunohistology. Thus, ART-18 treatment influences host responses differentially against kidney and heart allografts (modulation and depletion of IL-2R+ cells, respectively) despite increasing their survival comparably. The uremic state in the kidney model prevents elimination of infiltrating IL-2R+ mononuclear cells by a mAb directed specifically against them.

Animals↗

PubMed1990

Evidence that monoclonal antibodies against the 55kD subunit of the rat IL-2 receptor do not inhibit the development of suppressor cells generated in mixed lymphocyte culture.

Although the ability of Ts to prevent allograft rejection has been well established, their intrinsic characteristics and dependence upon lymphokines remain poorly defined. The cells from unmodified LEWxBN bulk 5-day rat MLR inhibit both proliferation in test MLR and generation of CTL, as well as prolonging the survival of donor-specific test cardiac allografts following adoptive transfer. We have examined the effects of a panel of mAb directed against functionally distinct epitopes on the p55 subunit of rat IL-2R on the generation and in vitro/in vivo activity of MLR-generated Ts. ART-18 (which blocks IL-2-dependent T cell growth) was the only mAb from the panel that profoundly suppressed alloreactive T cell proliferation in primary MLR (47.5%). However, the generation of Ts was never affected by any mAb (% suppression in test MLR = 40-60%). Neither ART-18 nor ART-65 (which does not affect T cell proliferation) interfered with the efficacy of Ts to inhibit CTL generation in fresh bulk MLR. Adoptive transfer of cells (3-10 x 10(6] from ART-18 or ART-65-modulated MLR into naive LEW rats prolonged (LEW x BN)F1 test cardiac allograft survival to 11-13 days (P less than 0.05 as compared with acutely rejecting hosts). All in vitro and in vivo effects exerted by MLR-generated cells were antigen-specific. In unmodified MLR, Ts were IL-2R+ (ca. 50% of total blasts), as shown by cell separation using magnetic beads. In contrast, in MLR with ART-18 added, Ts were primarily IL-2R- (ca. 10% of blasts). Thus, antirat p55 subunit IL-2R mAb do not inhibit MLR-generated Ts functionally operative in vitro and in vivo. IL-2R- Ts precursors requiring lymphokine(s) other than IL-2 may differentiate into IL-2-dependent Ts effectors. Such divergent IL-2 requirements for Ts growth in vitro may explain the Ts-sparing effects in allograft recipients treated with anti-IL-2R mAb.

Animals↗

PubMed1990

The mechanism of synergistic interaction between anti-interleukin 2 receptor monoclonal antibody and cyclosporine therapy in rat recipients of organ allografts.

Untreated anephric LEW rats die ca. 9 days following transplantation of LBNF1 kidney allografts. Although treatment with ART-18, a mouse antirat IL-2R mAb (300 micrograms/kg/day x 10 days), prolonged graft survival to ca. 3 weeks, the severely impaired renal function was comparable to untreated controls (creatinine levels 3-5 mg/dl). In contrast, simultaneous infusion of ART-18 and a very low dose of CsA (0.75 mg/kg x 10 days), marginally effective on its own, resulted in survival of greater than 45 days; the grafts exhibited relatively good function comparable to that in rats treated with full-dose (15 mg/kg/day) CsA. This beneficial biological effect did not depend upon elevated CsA trough levels in animals conditioned with both modalities. The CD4:CD8 ratio at the graft site was lowest (0.3-0.4) in recipients treated with ART-18 + CsA. Synergy between the two agents has been demonstrated by adoptive transfer studies in which nonspecific suppression has been conferred selectively by cells infiltrating kidney grafts in rats given ART-18 and CsA in concert but not separately (LBNF1 and WF test cardiac allograft survival ca. 12 days). In contrast, suppression in the recipient spleens was donor-specific; both CD4 and CD8 cells prolonged test graft survival. Immunohistological evaluation of renal allografts revealed that therapy with ART-18 or low-dose CsA alone failed to deplete IL-2R+ cells and prevent production of IL-2, IFN-g, and TNF. In contrast, the frequency of infiltrating IL-2R+ cells and elaboration of endogenous cytokines in non-uremic hosts receiving combination therapy was greatly depressed, stressing again synergistic interaction between ART-18 and CsA. Additionally, markedly reduced class II antigen induction, XL-fibrin deposition, and glomerulitis may also contribute to prolonged survival and satisfactory function of kidney allografts in this animal group.

Animals↗

PubMed1990

A sequence-specific DNA-binding protein that activates fushi tarazu segmentation gene expression.

The Drosophila segmentation gene fushi tarazu (ftz) is expressed at the cellular blastoderm stage in a pattern of seven transverse stripes; the stripes lie out of register with the segmental primordia, spanning alternate segmental boundaries. The zebra element, a 740-bp DNA sequence upstream of the ftz translational start, directs striped expression of lacZ when introduced into the fly genome. We have purified to homogeneity a sequence-specific DNA-binding factor, FTZ-F1, that binds to two sites located within the zebra element and to two sites within the ftz protein-coding sequence. FTZ-F1 DNA-binding activity is first detected in extracts of 1.5- to 4-hr embryos, coincident with the time of ftz expression in stripes; the activity then diminishes before reappearing during late embryo, larval, and adult stages. When one of the FTZ-F1-binding sequences in the zebra element is mutated by 2- or 4-base substitutions, the binding to FTZ-F1 is disrupted in vitro, and the intensity of lacZ expression is reduced in transformed embryos, especially in stripes 1, 2, 3, and 6. The results suggest that FTZ-F1 is a transcriptional activator necessary for the proper expression of the ftz gene.

Animals↗