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Biomedical subjects

T Eto

Publications and source records attributed to T Eto.

At least 19 recordsLinked to original sources

Isolation and identification of C-type natriuretic peptide in human monocytic cell line, THP-1.

In a survey for unknown bioactive peptides in mammalian cell lines, we isolated peptides exhibiting a strong relaxant effect on chick rectum from a phorbol ester-supplemented culture medium of the human monocytic cell line, THP-1. The peptide was deduced to be a C-terminal 29-residue peptide derived from a human C-type natriuretic peptide (CNP) precursor. CNP mRNA was also detected in the THP-1 cells, and expression of CNP gene and CNP concentration in the culture medium was found to be highly augmented by the stimulation of phorbol ester. Production of CNP in THP-1 cells suggests that CNP also functions as a local regulator in the blood cell-vascular system, although CNP has previously been recognized as a neuropeptide functioning in the central nervous system.

Amino Acid Sequence

Organ distribution and characterization of porcine peptides (VIP, CGRP and PHI) that increase cAMP in rat platelets.

Using an assay for rat platelet cAMP, we investigated the organ distribution of peptides that increase cAMP in rat platelets in porcine tissues. Marked activity was observed in the duodenum, pancreas and brain. By analysis with reverse phase high performance liquid chromatography (HPLC), three major peaks of activity were observed in porcine tissues. The first peak was vasoactive intestinal polypeptide (VIP), and the second peak was calcitonin gene-related peptide (CGRP). The third peak of activity was isolated from porcine duodenum. By analysis with a gas phase sequencer and with an amino acid analyzer, this peptide was identified as peptide histidine isoleucine (PHI). In a glucagon-secretin family of neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP) significantly increased platelet cAMP levels in a dose-dependent manner; however, glucagon did not. These results suggest that not only VIP and CGRP but also PHI and PACAP act upon platelets, as well as vascular tissues.

Amino Acid Sequence

Isolation and characterization of peptides which act on rat platelets, from a pheochromocytoma.

An increase in the cellular concentration of cAMP leads to the inhibition of platelet aggregation. We have been investigating endogenous peptides which inhibit platelet function, using an assay which detects increase in platelet cAMP. Compared with the human adrenal medulla, a pheochromocytoma (PC) contained abundant peptides that elevate platelet cAMP. About 90% of the activity was found in the SP-III fraction which contained strongly basic peptides. From the SP-III fraction, peptides P-1, P-2 and P-3 were purified to homogeneity as endogenous peptides which elevated platelet cAMP. A gas phase sequencer was used to identify these peptides as follows: P-1 = vasoactive intestinal peptide (VIP); P-2 = calcitonin gene related peptide-I (CGRP-I); P-3 = CGRP-II. It is well known these peptides are potent vasorelaxants. VIP and CGRP-I significantly increased platelet cAMP levels 15- and 6-fold, respectively. These results suggest that VIP and CGRP-I and -II act upon platelets as well as upon vascular tissue.

Adrenal Gland Neoplasms

Intussusception of an appendiceal mucocele: report of a case.

A 66 year old Japanese female was admitted to our department for the examination and treatment of a mass in the cecum. She had experienced no symptoms or signs other than a positive test result for fecal occult blood. The mass in the cecum was confirmed by barium enema, colonofiberscopy and CT scanning. The presumptive diagnosis was a submucosal tumor of the cecum, however, a laparotomy subsequently revealed intussusception of an appendiceal mass. An ileocaecal resection with an ileocolic anastomosis was therefore performed and the mass was histologically diagnosed as a mucocele of the appendix. This patient is only the 24th case of intussusception of a mucocele of the appendix to be reported in Japan. A review of the available literature on this condition follows the case report.

Aged

Biological characteristics of CD7 positive acute myelogenous leukaemia.

We studied the biological characteristics of CD7+ acute myelogenous leukaemia (AML). We diagnosed nine out of 88 consecutive AML cases as CD7+ AML based on myeloperoxidase positivity and surface antigen expression. In eight of these nine cases more than 20% of leukaemic blasts were found to coexpress both CD7 and a myeloid-associated antigen, CD33, by a two-colour flow-cytometric assay, while in the remaining case more than 90% of blasts were positive for CD7 and myeloperoxidase. CD7+ AML was most frequently observed in M1 among AML subtypes according to the FAB classification. An early stage-specific antigen, CD34 was also expressed on leukaemic blasts from eight of these nine cases. Neither the T-cell receptor (TcR)-beta nor the TcR-gamma gene was clonally rearranged in any of the cases. We then studied the proliferative responses to stimulation by various growth factors. Among interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF), IL-3 showed the strongest stimulatory effect on DNA synthesis and leukaemic blast colony formation in 8/9 and 6/8 CD7+ AML cases examined, respectively. On the other hand, the strongest stimulatory effect exerted by IL-3 on blast colony formation was observed in only six out of the 33 CD7- AML cases examined. Furthermore, CD7+ AML blasts could proliferate in response to stem cell factor (SCF); SCF alone showed stimulatory effects on blast colony formation (7/8 cases), and in 5/7 SCF-responding cases, stimulatory effects of SCF were more potent than those of IL-3. In addition, SCF enhanced blast colony formation synergistically with IL-3 in four of these seven cases. These data suggest that progenitor cells of CD7+ AML may possess the biological properties characteristic of immature haematopoietic stem cells.

Adolescent

Evaluation of atrial, ventricular and atrioventricular septal defects by cine magnetic resonance imaging.

Cine magnetic resonance imaging (MRI) was performed on 20 patients (mean age: 5.3 +/- 4.4 years) with atrial, ventricular, or atrioventricular septal defects for evaluation of cardiac structure and blood flow. Prior to cine MRI, electrocardiographically gated MRI using multislice acquisition was performed on all patients to localize optimal slice location. Cine-MRI was obtained with a 30 degrees flip angle, 15 msec echo time, and 30 msec pulse repetition time, on a 256 x 256 or 128 x 128 acquisition matrix. Abnormalities of cardiac structure were well defined in all patients by gated cardiac imaging. In 18 of the 20 patients, cine-MRI was able to detect shunt flow, visualized as a low intensity signal in comparison with the surrounding blood flow. Cine-MRI can provide not only accurate anatomy of cardiac structures but functional assessment of the cardiac chamber, wall topology and flow relations. Cine-MRI will become an important noninvasive technique for assessment of anatomy and physiology in congenital heart disease.

Abnormalities, Multiple

Hypertension in an adult with unilateral renal dysplasia.

We report a 29-year-old Japanese female with severe hypertension and unilateral renal dysplasia, which is rarely found in adults. The involved kidney was surgically removed and then the blood pressure fell to borderline levels without any changes in plasma renin activity or plasma aldosterone concentration. Histological examinations revealed typical renal dysplasia without hyperplasia of the juxtaglomerular apparatus. Unilateral renal dysplasia may be a cause of secondary hypertension in adults, though the mechanisms are still unknown.

Adult

Horseshoe kidney and membranous glomerulonephritis with cold activation of complement.

A 48-year-old woman was admitted to our hospital because of proteinuria associated with persistent hypocomplementemia. Intravenous pyelography indicated the presence of horseshoe kidney without other abnormalities. Hypocomplementemia was caused by cold activation of complement. There were some findings suggestive of chronic liver disease (positive HCV antibody, hypergammaglobulinemia, low cholinesterase, etc.). Percutaneous renal biopsy showed the features of multiple evolutional phases of membranous glomerulonephritis.

Cold Temperature

[A case of hepatocellular carcinoma responding to intraarterial infusion of epirubicin and mitomycin C].

A 64-year-old male was admitted for treatment of hepatocellular carcinoma. He was diagnosed as having many tumors in the area of S6 and the AFP level was elevated to 878 ng/ml. Initially, intraarterial infusion of Epirubicin only was not effective. After the first course of treatment, tumors increased in size and the AFP level was elevated. Next, intraarterial infusion of Epirubicin and Mitomycin C was performed. After the second course of treatment, the AFP level decreased from 5,006 ng/ml to 754 ng/ml and the tumors had almost completely disappeared on angiography. The tumors continued to decrease in size and thereafter the AFP level decreased to 10 ng/ml and was not elevated. The tumors almost completely disappeared in this case, and the coadministration of Epirubicin and Mitomycin C provided effective.

Antineoplastic Combined Chemotherapy Protocols

Platelet neuropeptide Y in spontaneously hypertensive rats.

OBJECTIVE: To investigate the pathological role of platelet neuropeptide Y (NPY) in genetically hypertensive rats, we measured the platelet content and plasma concentration of immunoreactive (ir)-NPY in hypertensive and normotensive rats and examined the aggregating ability of rat platelets and the NPY releasing reaction in each of these rat types. In addition, we purified platelet NPY and determined its amino acid sequence. DESIGN AND METHODS: To characterize immunoreactive NPY in rat platelets, rat platelet NPY was purified to homogeneity and the purified peptide was analysed by gas-phase sequencer. Platelet content and plasma concentration of NPY was measured by a sensitive radioimmunoassay for NPY. Aggregating ability was examined by a turbidimetric method; aggregation was recorded for 5 min and the maximum aggregation was read. RESULTS: Rat platelet NPY was purified and the amino acid sequence was determined to be YPSKPDNPGEDAPAEDMARYYSALRHYINLITRQRY. The platelet content of ir-NPY in 5-, 10-, and 15-week-old spontaneously hypertensive rats (SHR) was higher than that in Wistar-Kyoto (WKY) rats of the same age. The platelet content of ir-NPY in 10-week-old stroke prone-SHR was also higher than that in 10-week-old WKY rats. No differences were observed between any of the pairs in any WKY rats, SHR or stroke-prone SHR group with regard to the plasma concentration of ir-NPY. Ir-NPY was not released from rat platelets when adenosine diphosphate was used for aggregation. However, NPY was released from the platelets when they were aggregated by collagen and, furthermore, in this case the amount of NPY released from platelets was greater in SHR than in WKY rats. CONCLUSION: That the platelet content of NPY in SHR (and stroke-prone SHR) was higher than that in WKY rats seems to be an important genetic characteristic of SHR. As NPY is a potent vasoconstrictor, it may be involved in the progression of vascular lesions.

Amino Acid Sequence

Effects of brain natriuretic peptide-45, a circulating form of rat brain natriuretic peptide, in spontaneously hypertensive rats.

Rat brain natriuretic peptide-45 (rat BNP-45) has recently been isolated from rat heart and shown to be a circulating form of rat BNP. We investigated the effects of rat BNP-45 in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and compared them with those of rat alpha-atrial natriuretic peptide (alpha-ANP). BNP-45 was a potent natriuretic and hypotensive agent in both strains. The effects were comparable with those of alpha-ANP and were far greater than those of porcine BNP-26 reported previously. In SHR blood pressure decreased more than in WKY following injection of the highest dose (2.0 nmol/kg) of BNP-45 or alpha-ANP. However, WKY were more susceptible than SHR to BNP-45 for diuresis, natriuresis and urinary cGMP excretion. Moreover, a high dose of BNP-45 led to a prolonged lowering of blood pressure and urinary cGMP excretion compared to alpha-ANP, and these features were prominent in WKY. BNP-45 disappeared more slowly than alpha-ANP when the two peptide (2.0 micrograms) were injected i.v. in WKY. Thus, rat BNP-45 and alpha-ANP had comparable hypotensive and natriuretic potency; however, the action and plasma half-life of rat BNP-45 were more prolonged.

Amino Acid Sequence

Effects of interleukin-4 and interleukin-6 on the proliferation of CD34+ and CD34- blasts from acute myelogenous leukemia.

We studied the effects of interleukin-4 (IL-4) and IL-6 on the growth of leukemic blasts from 40 patients with acute myelogenous leukemia (AML). Patients were selected on the basis of negativity for a series of B-cell antigens including CD10 and CD19. Twenty-one cases were CD34-positive (CD34+) (greater than 15% of blasts) and the remaining 19 were CD34-negative (CD34-) (less than 3% of blasts). IL-4 alone (100 U/ml) could stimulate either DNA synthesis (with greater than 2.0 stimulation index) or leukemic blast colony formation in 24 of 40 AML patients. In the presence of other growth factors, IL-4 showed divergent effects on IL-3-, granulocyte-macrophage colony-stimulating factor-, granulocyte colony-stimulating factor-, or erythropoietin-dependent colony formation. These effects of IL-4 were observed in both CD34+ and CD34- AML cases. IL-6 (100 U/mL) alone could not stimulate DNA synthesis and blast colony formation except for one CD34+ case. On the other hand, IL-6 showed synergistic effects on IL-3- and IL-4-dependent blast colony formation in 10 of 12 and 7 of 9 CD34+ AML cases, respectively. Among CD34- AML cases, such synergism was seen only in 1 of 12 cases for IL-3-dependent colony formation and in 3 of 7 cases for IL-4-dependent colony formation. The divergent effect of IL-4 and the synergistic effect of IL-6 were also observed in purified CD34+ leukemic blast populations, indicating that these phenomena are not mediated by accessory cells. The present study suggests that IL-4, alone or in combination with other growth factors, has divergent effects on the growth of AML progenitors irrespective of the CD34 expression, and that IL-6 acts synergistically with IL-3 or IL-4 on the growth of leukemic progenitors preferentially in CD34+ AML.

Adolescent

Increased secretion of brain natriuretic peptide and atrial natriuretic peptide, but not sufficient to induce natriuresis in rats with nephrotic syndrome.

The levels of immunoreactive brain natriuretic peptide (ir-BNP) and immunoreactive atrial natriuretic peptide (ir-ANP) were evaluated by radioimmunoassay in both the atrium, ventricle and plasma of adriamycin-induced nephrotic rats and control rats. There was no difference in right and left atrial concentrations of ir-BNP, however, a higher right atrial concentration of ir-ANP was observed in nephrotic rats than in controls (p less than 0.01). The ventricular ir-BNP and ir-ANP were increased in nephrotic rats compared to controls (BNP: p less than 0.001, ANP: p less than 0.001). Cardiac BNPs were composed of pro-BNP (gamma-BNP) and its C-terminal 45-amino-acid peptide (BNP-45). The ratio of BNP-45/gamma-BNP in nephrotic rats was higher than that of controls in both atria and in the ventricle. Plasma ir-BNP and ir-ANP were significantly higher in nephrotic rats than in controls (BNP: p less than 0.001, ANP: p less than 0.001), and each level was negatively correlated with urinary sodium excretion in nephrotic rats (BNP: r = -0.84, p less than 0.001, ANP: r = -0.88, p less than 0.001). These results suggest that production and secretion of both BNP and ANP are concomitantly stimulated by a decreased renal ability to eliminate sodium and water, but this secretion is insufficient to induce effective natriuresis in nephrotic rats.

Animals

Tuberculous liver abscess with bronchobiliary and gastrobiliary fistulae--a case report.

A rare case of a primary tuberculous liver abscess with bronchobiliary and gastrobiliary fistula formation is presented herein, emphasizing the difficulty in establishing its diagnosis. The clinical course was complicated and a wide range of antibiotics administered repeatedly, based on the initial diagnosis of a liver abscess, until the final diagnosis of a tuberculous liver abscess was established by histopathological reinvestigation of the resected liver specimen. Thereafter, antituberculous chemotherapy proved extremely effective for the alleviation of symptoms, reduction of the abscess and closure of the fistulae.

Adult

Common bile duct exploration--primary closure of the duct with retrograde transhepatic biliary drainage.

A new method of retrograde transhepatic biliary drainage (RTBD) using an RTBD tube with primary closure of the common duct was investigated with special reference to the usefulness and feasibility of this procedure. At operation, an atraumatic vinyl chloride tube was inserted from a choledochotomy incision and in most cases advanced via the left hepatic duct to the liver surface, which was then penetrated. After the choledochotomy incision had been primarily sutured, the RTBD tube was fixed to the abdominal wall. This drainage method was applied to 71 patients as an alternative to the conventional T-tube drainage and its effect on bile drainage was prominent. The insertion of an RTBD tube did not influence liver function tests and an RTBD tube cholangiography revealed no severe deformity at the primary closure site of the bile duct. The most common complication was movement of the optimal site for stenting of the bile duct, however, no serious complications were encountered. On average, the RTBD tube was removed on the 16th postoperative day, the mean postoperative stay in hospital being 22 days. These findings suggest the need for a prospective randomized clinical trial to prove the usefulness and feasibility of primary bile duct closure using our drainage method.

Bile