Biomedical subjects

J Taguchi

Publications and source records attributed to J Taguchi.

At least 91 records · Page 5Linked to original sources

PubMed1994

A fumagillin derivative angiogenesis inhibitor, AGM-1470, inhibits activation of cyclin-dependent kinases and phosphorylation of retinoblastoma gene product but not protein tyrosyl phosphorylation or protooncogene expression in vascular endothelial cells.

Fumagillin analogue AGM-1470 potently inhibits angiogenesis with a minimal toxicity in vivo and is expected to be of therapeutic use as a powerful antitumor agent (Ingber et al., Nature, 348:555-557, 1990). In the present study, we have investigated the effects and the mechanism of action of AGM-1470 on cultured human umbilical vein endothelial cells. AGM-1470 acts directly on endothelial cells to inhibit growth factor-induced DNA synthesis, with half maximal and maximal effects obtained at approximately 2 x 10(-10) and 5 x 10(-9) M, respectively. AGM-1470 does not inhibit early G1 mitogenic events, such as cellular protein tyrosyl phosphorylation or the expression of immediate early genes c-fos and c-myc, but potently inhibits phosphorylation of RB protein, a tumor suppressor retinoblastoma gene product. The later addition of AGM-1470 up to 3 h after the growth factor stimulation still exerts full inhibitory effects on both DNA synthesis and RB phosphorylation, suggesting that the major site of action of AGM-1470 is located relatively late in the G1 phase. AGM-1470 inhibits growth factor-induced activation of candidate RB kinases cdc2 and cdk2 but fails to inhibit them directly in vitro. AGM-1470 completely abolishes the growth factor-induced mRNA expression of cdc2 and cyclin A and partially inhibits that of cyclin E but has little effect on the mRNA level of cdk2, cdk4, or cyclin D1. These results indicate that angioinhibitory action of AGM-1470 involves suppression of mRNA expression of specific members of cdks and cyclins and of activation of both cdc2 and cdk2 kinases in endothelial cells.

CDC2 Protein Kinase↗

PubMed1994

Autoradiographic distribution of [3H]YM-09151-2, a high-affinity and selective antagonist ligand for the dopamine D2 receptor group, in the rat brain and spinal cord.

We determined the regional distribution of the dopamine D2 receptor group in the rat central nervous system by quantitative receptor autoradiography with a high-affinity and selective antagonist, [3H]YM-09151-2. Saturation and competition experiments demonstrated that the binding of [3H]YM-09151-2 to striatal sections was saturable (Bmax = 37.3 fmol/section), of high affinity (Kd = 0.315 nM), and was inhibited selectively by prototypic D2 ligands. The anatomical localization of binding sites was determined by comparison of autoradiograms and the original 3H-ligand-exposed sections stained with cresyl violet. Very high levels of [3H]YM-09151-2 binding were found in the caudate-putamen, nucleus accumbens, tuberculum olfactorium and the insula of Calleja, to each of which midbrain dopaminergic neurons project densely. High levels of binding were also observed in other regions rich in dopaminergic neurons and fibers including the glomerular layer of the olfactory bulb, the intermediate lobe of the pituitary, lateral septum, substantia nigra pars compacta, interfascicular nucleus, dorsal raphe nucleus, locus coeruleus, and nucleus of the solitary tract. Some regions poor in dopaminergic innervation, however, had high levels of [3H]YM-09151-2 binding including the molecular layer of gyrus dentatus, all layers of CA1 and the nonpyramidal layer of CA4 of hippocampus, and the deeper layer of medial entorhinal cortex. Motor neurons present in brainstem motor nuclei and spinal ventral horn were also strongly labeled. Neocortical, cerebellar, and thalamic regions had low levels of binding, except lobules 9-10 of the cerebellum, the olivary pretectal nucleus, zona incerta and lateral mammillary nucleus, in which moderate to high levels of binding were detected. Our findings concerning the widespread but region-specific localization of [3H]YM-09151-2 binding sites in the brain and spinal cord may prove useful for analyzing various dopaminergic functions in the central nervous system.

Animals↗

PubMed1994

Suppression of neointimal smooth muscle cell accumulation in vivo by antisense cdc2 and cdk2 oligonucleotides in rat carotid artery.

Deendothelializing balloon injury of rat carotid artery results in progressive intimal smooth muscle cell accumulation and luminal stenosis over 14 days after injury. We have found transient rises (approximately 3-fold maximal increases over the uninjured control value) of the kinase activities of both cdc2 and cdk2, key molecules for cell cycle progression, in the injured carotid artery along with the development of intimal proliferation. The topical application of the antisense, but not the sense, cdc2 and cdk2 phosphorothioate oligodeoxynucleotides dissolved in F127 pluronic gel around the freshly injured artery resulted in reductions of the intimal smooth muscle cell accumulation by 47% and 55% respectively, as estimated by an intimal to medial cross-sectional area ratio, with concomitant decreases in cdc2 and cdk2 kinase activities. These results indicate that both cdc2 and cdk2 kinases are involved in intimal smooth muscle cell accumulation after balloon angioplasty and suggest a potential usefulness of the antisense cdc2 and cdk2 oligonucleotide therapy for arterial stenosis.

Angioplasty, Balloon↗

PubMed1994

Unique T cell differentiation markers: gangliosides with cholera toxin receptor activity on murine fetal thymocytes.

Cholera toxin B subunit receptors (CTBR; gangliosides GM1a and GM1b-GalNAc-Gal) and GM1b-type gangliosides were examined during T cell development in BALB/c mice by FACS or TLC immunostaining. Sixty-two percent of CD4-8- early fetal thymocytes express CTBR [58% low affinity (GM1a+), 4% high affinity (GM1a2+)] at 13 days gestation (Day 13); GM1a2+ was expressed preferentially on Thy-1+ fetal thymocytes after Day 13. GM1a2+ Thy-1+ cells increased from 4% on Day 13 to 95% on Day 17. Surface GM1a2+ decreased beginning on Day 15 while GM1b-GalNAc-Gal (and CD4 and CD8) increased. GM1b-type+ cells increased from 8% on Day 13 to 51% on Day 17 and then decreased to 16% at 4 weeks; few asialo GM1+ cells (< 5%) are seen during gestation. Thus, synthesis of GM1a- and GM1b-type series was active until Days 15 and 17, respectively, and then was suppressed; GM1b-GalNAc-Gal was synthesized from GM1b following Gestational Day 15. GM1a- and GM1b-type identify immature T cells in mice, while GM1b-GalNAc-Gal identifies mature T cells.

Animals↗

PubMed1994

Neuropeptide participation in canine laryngeal sensory innervation. Immunohistochemistry and retrograde labeling.

We investigated the quantitative participation of calcitonin gene-related peptide (CGRP), substance P (SP), and leu-enkephalin (ENK) in canine laryngeal sensory innervation by immunohistochemistry in combination with retrograde labeling using the recently introduced retrograde tracer cholera toxin subunit B-conjugated gold (CTBG). In the nodose ganglion, neurons labeled from the internal branch of the superior laryngeal nerve with CTBG were investigated immunohistochemically by means of antisera against CGRP, SP, and ENK. The percentages of neurons immunoreactive to each neuropeptide were as follows: CGRP 81.5%, SP 24.5%, and ENK 7.0%. These results suggest that CGRP is the main sensory neurotransmitter in canine laryngeal sensory innervation.

Animals↗

PubMed1994

Squamous cell carcinoma of the ovary--a case report.

A 68-year-old woman presented a one-month history of lower abdominal pain and weight loss, and was admitted to our hospital. On physical examination, a large hard mass was palpated in her right lower abdomen. An ultrasonograph and computed tomographic (CT) scan revealed a right ovarian tumor that measured 6.9 x 4.9 cm in size. A total hysterectomy and bilateral salpingo-oophorectomy were performed. The postoperative diagnosis of the tumor was squamous cell carcinoma (SCC) of the ovary. She died of infection and disseminated intravascular coagulation 5 months after surgery. The clinical and autopsy examinations did not show the primary lesions of SCC except in the right ovary. Mature cystic teratoma, Brenner tumor and endometriosis, which are ordinary regarded as the histogenesis of ovarian SCC, were not found, but a few surface epithelial inclusion cysts with squamous metaplasia were observed in non-cancerous area of the right ovary, and the contiguous transition from the metaplastic cyst wall to SCC was confirmed by stepwise serial sections. The present case suggests that the surface epithelium of ovary could be the fourth possibility in the histogenesis of the ovarian SCC.

Aged↗

PubMed1994

Calcitonin gene-related peptide-like immunoreactive motoneurons innervating the canine inferior pharyngeal constrictor muscle.

The percentage of the calcitonin gene-related peptide-immunoreactive motoneurons (Mn) in the nucleus ambiguus (NA) innervating the canine inferior pharyngeal constrictor muscle was examined using the cholera toxin B subunit-gold (CTBG) as a retrograde tracer and by immunohistochemistry. Labeled neurons with CTBG (CTBG MNs) from the thyropharyngeal muscle (TP) were located in the dorsomedial division of the rostral part of the NA and the average percentage of neurons with CGRP immunoreactivity was 70.3%. CTBG MNs from the cricopharyngeal muscle (CP) were located in the dorsal division of the rostral part of the NA and the average percentage of neurons with CGRP immunoreactivity was 21.2%. This low percentage of CGRP immunoreactivity is noteworthy and supports the idea that the CP is a particular striated muscle in function and innervation manner.

Animals↗

PubMed1994

Topical application of AT1 receptor antagonists prevents medial and neointimal proliferation after balloon injury.

Angiotensin II plays an important role in neointima formation after vascular injury. A rat model of carotid artery injury was used i) to investigate the effect of single topical application of angiotensin II subtype 1 (AT1) receptor antagonists (CV11974, DuP753) in suppressing medial proliferation at day 2 and neointimal proliferation at day 14, and ii) to investigate the antiproliferative effects of additional application of L-arginine (a nitric oxide precursor). Drugs mixed in 25% (W/W) solutions of F127 pluronic gel were applied topically to injured vessels. Early medial proliferation of smooth muscle cells, assessed by the S-bromo-2'-deoxyuridine labelling index, was significantly suppressed by application of CV11974 (5 mg/kg), 7.5% +/- 2.2% vs. 19% +/- 3.9% in the control group. The intima/media ratio following CV11974 (10 mg/kg) or DuP753 (12.5 mg/kg) at day 14 was significantly lower than that in the control group (42% +/- 7%, 43% +/- 14%, and 123% +/- 11%, respectively). Additional application of L-arginine seemed to increase effectiveness, but was not statistically significant. In conclusion, single topical application of AT1 receptor antagonists was effective in suppressing early medial proliferation and neointima formation after balloon injury, suggesting that they may be clinically useful after angioplasty or vascular surgery.

Administration, Oral↗

PubMed1994

[Auer-rod-like bodies in plasma cells in patient with plasma cell dyscrasia].

Auer-rod-like bodies were found in plasma cells from a 74-year-old man with plasma cell dyscrasia. These bodies exhibited red purple staining by May-Giemsa staining and were indistinguishable from Auer bodies often found in acute myeloid leukemia. These bodies, however, failed to stain with peroxidase and showed acid phosphatase positivity. Bone marrow examinations were performed three times at the sternum or iliac crest. The proportions of plasma cells were 4.4%, 3.4% and 3.8%. The Auer-rod-like bodies were found in 0.05% (2/3824), 0.07% (4/6883) and 0.08% (2/2656) of the plasma cells.

Aged↗

PubMed1993

Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission.

Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

Adolescent↗

PubMed1993

Angiotensin converting enzyme inhibitors or DuP753 prevent neointimal formation following balloon injury with single topical or multiple systemic application.

Angiotensin II plays an important role in neointimal formation after vascular injury. Our objectives were 1) to investigate the difference between angiotensin converting enzyme inhibitors (captopril, delapril) and an angiotensin II subtype 1 (AT1) receptor antagonist (DuP753) in suppressing neointimal proliferation; and 2) to investigate the antiproliferative effects of these drugs given topically to the injured vessels. All these treatments effectively prevented neointimal formation (p < 0.01). Even a single topical application of either type of drug with F127 pluronic gel to be injured vessel after ballooning is found to be significantly effective probably due to the inhibition of smooth muscle cell migration (p < 0.01). Multiple systemic application of angiotensin converting enzyme inhibitors was more effective than that of DuP753 at the same blood pressure level. The effectiveness of topical application of these drugs suggests clinical usefulness after angioplasty or vascular surgery.

Administration, Topical↗

PubMed1993

Myocardial reperfusion can be predicted by myoglobin/creatine kinase ratio of a single blood sample obtained at the time of admission.

To evaluate noninvasive markers for determining the reperfusion status without coronary angiography (CAG) or serial blood sampling in patients with acute myocardial infarction (AMI), two markers were examined: (1) serum myoglobin (Mb) level and (2) serum myoglobin/creatine kinase ratio (Mb/CK). Before emergency CAG a blood sample was drawn from 72 AMI patients within 6 hours after the onset of AMI. CAG revealed thrombolysis in myocardial infarction grades (TIMI) 0 to 1 in 56 and TIMI 2 to 3 in 16 patients (spontaneous reperfusion). No patients had received thrombolytic therapy before admission. TIMI 0 to 1 patients were characterized with lower Mb levels than TIMI 2 to 3 patients at admission (346 +/- 476 vs 1558 +/- 2005, mean +/- SD, p < 0.001). Furthermore, the mean Mb0/CK0 ratio in TIMI 2 to 3 patients, who had already achieved the reperfusion at admission, was significantly higher than that in patients with TIMI 0 to 1 patients (6.5 +/- 3.9 vs 2.1 +/- 1.8, mean +/- SD, p < 0.0001). When Mb0/CK0 > 5.0 was assumed to indicate the sufficient reperfusion at admission, the sensitivity, specificity, and accuracy evaluating the reperfusion status were 75%, 96%, and 92%, respectively. It can be concluded that the reperfusion status can be predicted satisfactorily by a single blood sample obtained at the time of admission without CAG.

Aged↗

PubMed1993

L-arginine inhibits neointimal formation following balloon injury.

Nitric oxide (NO)-generating vasodilators inhibit the mitogenesis and proliferation of cultured vascular smooth muscle cells. We investigated the role of NO in the vascular response to arterial injury by administering L-arginine (precursor of NO), D-arginine or N-nitro L-arginine methylester (NAME; an inhibitor of NO synthesis) to a rat model of balloon catheter-induced left carotid artery injury. Two weeks after the balloon injury, animals that received both oral (1.25 g/l water) and local (10mg in gel) administration of L-arginine showed suppression of neointimal proliferation with no change in systolic blood pressure. Medial proliferation was potentiated in NAME-treated animals with a higher blood pressure. Tissue cGMP content (representative of NO generation) of the injured arteries was similar to that of normal arteries with intact endothelium. These findings suggest that a higher local concentration of NO produced from L-arginine can inhibit the migration and proliferation of smooth muscle cells in the injured vascular wall.

Animals↗

PubMed1993

Elevation of neuroactive substances in the cortex of cats during prolonged focal ischemia.

Sustained accumulation of excitatory amino acids and other neuroactive substances may contribute to the delayed progression of infarction in focal ischemia. Following occlusion of the left middle cerebral artery (MCAO), extracellular amino acid and purine catabolite concentrations as well as local CBF were repeatedly monitored for up to 15 h in auditory (A) and somatosensory (SF) cortices of seven halothane-anesthetized cats using microdialysis/HPLC and hydrogen clearance. MCAO resulted in persistent reduction of local CBF, which was more severe in A (n = 6) than in SF (n = 6). Accordingly, higher transmitter amino acid and purine catabolite concentrations were found in A than in SF during ischemia. Aspartate, glutamate, and gamma-aminobutyrate (GABA) as well as hypoxanthine and inosine reached maximum levels 1-2 h after onset of ischemia (15-, 7-, 31-, 8-, and 14-fold increases, respectively). Maximum levels remained almost constant, with the exception of inosine, which decreased subsequently. Glycine seemed to increase with prolonged ischemia and reached maximum levels (10-fold) 15 h after occlusion. Adenosine peaked 30 min after occlusion (54-fold) and decreased thereafter to control levels within 1-2 h. One hour after occlusion, CBF thresholds for amino acid elevation were lower (glutamate and GABA approximately 20 ml 100 g-1 min-1 and glycine approximately 10 ml 100 g-1 min-1) than 6 and 15 h after occlusion (thresholds for all amino acids at approximately 30 ml 100 g-1 min-1). These results indicate that in prolonged ischemia, excitotoxicity is an important factor, particularly in border zones of ischemic foci.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1993

Fatal acute hepatitis B virus infection while receiving immunosuppressants after renal transplantation.

A 47-year-old man with acute hepatitis B virus (HBV) infection who had been receiving immunosuppressants after renal transplantation developed progressive liver failure. During the clinical course (approximately 7 months), anti-HBc IgM antibody and HBV-DNA polymerase levels remained high, but the serum alanine aminotransferase (ALT) level was consistently less than 150 K.U. Histopathologic examination of the liver showed submassive hepatic necrosis without significant inflammation accompanied by marked fibrosis. Most hepatocytes showed strong nuclear expression of HBc antigen by immunohistochemical staining and electron microscopy revealed numerous intranuclear core-like particles. Hepatitis B virus infection in immunosuppressed individuals occasionally insidiously progresses, resulting in liver failure. The clinical course of such patients thus merits close scrutiny.

Acute Disease↗

PubMed1993

Intrahepatic and extrahepatic biliary papillomatosis.

We report a case of biliary papillomatosis that occurred 8 years after resection of a bile duct tumor. In 1982, a 63-year-old man underwent a cholecystectomy because of cholelithiasis. At operation, a solitary tumor was found in the left intrahepatic bile duct, and a lateral hepatic segmentectomy was performed. The tumor was diagnosed as a benign papillary adenoma. In 1990, mild liver dysfunction was revealed in a routine medical examination. Ultrasonography and computed tomography showed a solid tumor measuring approximately 6 cm in diameter in the left hepatic duct. There was no appearance of jaundice during the course. In 1991, a partial hepatic resection and a bile duct resection were performed. At operation, two tumors were found and removed. These tumors were essentially the same as the bile duct tumor resected 8 years ago. They were diagnosed as biliary papillomatosis.

Bile Duct Neoplasms↗

PubMed1992

Bypass surgery for aortitis syndrome: aortocarotid bypass with saphenous vein graft.

In seven patients with Takayasu arteritis, symptomatic cerebral ischemia was successfully treated by extracranial bypass surgery. We performed 14 surgical procedures, which included aortocarotid bypass, axilloaxillary bypass, carotid-vertebral bypass, subclavian-carotid bypass, axillocarotid bypass, carotid-carotid bypass, carotid-subclavian bypass, carotid-axillary bypass, and thyreocervical-carotid anastomosis. Among those the aortocarotid bypass was the most common procedure performed--six occasions in four cases. The others were less common procedures, each performed only one time. The saphenous vein was used for the graft in 12 of the procedures. An artificial graft made of Gore-Tex (6-mm inner diameter) was utilized in two cases. Patency of the grafts was adequate and no mortality or serious postoperative complication was encountered. Asymptomatic infarction developed in one patient. We analyze these procedures in detail and stress the usefulness of aortocarotid bypass with a saphenous vein graft.

Adult↗

PubMed1992

Pathomorphologic study of pale bodies in hepatocellular carcinoma.

Pathomorphological and immunohistochemical studies were conducted on cases of hepatocellular carcinoma (HCC) with pale bodies (PB). HCC containing PBs was seen in 6 (5.7%) of 106 consecutively resected HCC cases. It was of interest that varying degrees of sclerotic change were found in 4 of the 6 cases and a certain correlation between PBs and sclerotic change of HCC tissue was suggested. Histologically, PBs were identified as a pale amorphous substance with a distinct margin and most of PBs occupied the entire cytoplasm of the cancer cells. PBs were practically negative for periodic-acid Schiff, and were also negative for phosphotungstic acid hematoxylin and orcein stains. Ultrastructurally, PBs were found to be a mass of granular or fibrillar materials having a single-layered limiting membrane, and dilated rough endoplasmic reticular (rER) were also found in the vicinity of PBs, suggesting the presence of a close relationship between rough endoplasmic reticula and PBs. Most PBs were found to be strongly positive for anti-fibrinogen antibody and some of them were weakly positive for anti-albumin, but were solely negative for other antibodies such as anti-HBs antigen, anti-alpha-1-antitrypsin, and anti-ferritin. According to those findings, PBs were thought to be fibrinogens accumulating in cystic rER due to a defective intracellular transport or an excretion disturbance.

Aged↗