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Biomedical subjects

T Eto

Publications and source records attributed to T Eto.

At least 127 records · Page 7Linked to original sources

[A case of primary lung cancer presenting as pneumothorax].

A 62-year-old man presented pneumothorax as a first manifestation of lung cancer was described. The patient complained right side chest pain and dry cough of 6 days duration. On the day of admission, a chest radiograph showed a large pneumothorax on the right. After 3 days of tube drainage, the lung was re-expanded and a chest radiograph showed a mass density above the right hilum. A chest CT revealed a cavitating tumor of the right upper lobe with a fistula to the pleural space. Right upper lobectomy was performed, and the histology was squamous cell carcinoma. The cause of pneumothorax was bronchopleural fistula secondary to rapid growth of the cancer. Pneumothorax due to primary lung cancer is rare and the prognosis is poor because the cancer was advanced stage or diagnosis of cancer was delayed in the literature review. Lung cancer should always be considered as a possible cause of pneumothorax, and it is important to diagnose lung cancer as soon as possible.

Carcinoma, Squamous Cell↗

Allogeneic peripheral blood stem cell transplantation for standard-risk leukemia. A multicenter pilot study: Japanese experience. Japan Blood Cell Transplantation Study Group.

A multicenter phase II study of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was conducted. Twenty-two patients (median age, 36 years) with standard-risk leukemia were transplanted with G-CSF-mobilized PBSC from an HLA-identical sibling donor, and received cyclosporine and methotrexate for GVHD prevention. Median days to ANC >500/microl and platelets >50,000/microl were 12 (9-20) and 16 (11-32), respectively. Grade II-IV acute GVHD developed in 6/21 (29%) and extensive chronic GVHD in 12/20 (60%). These observations indicate that allo-PBSCT is characterized by rapid hematologic engraftment, no increase of acute GVHD and an increased risk of chronic GVHD, and can be used as an alternative to allogeneic bone marrow transplantation.

Adolescent↗

[Coronary angiography provides considerable in vivo pathophysiological information on coronary artery disease].

Coronary cineangiography (CAG) has various limitations and pitfalls, but is widely accepted for evaluating coronary circulation. The interpretation of CAG focuses mainly on the extent and location of coronary artery disease. However, CAG can also provide considerable and varied in vivo pathophysiological information on coronary artery disease as follows: Certain in vivo angiographic coronary morphologies are indicative of histological findings, such as ruptured atheromatous plaque with/without overlying thrombus. Such morphologies are commonly found in patent ischemia- or infarct-related arteries of patients with acute coronary events in both the acute phase and one month after standard medication, and the diseased portion with the morphology is highly specific to the culprit site. The rupture of plaque and overlaid thrombus is just as important in patients with acute coronary events who survive as in patients who die. Diseased sites with complex lesions are prone to progress toward clinical ischemic episodes. The severity of coronary narrowing immediately after acute coronary events does not influence later left ventricular function if antegrade coronary blood flow without distal filling delay is preserved. Coronary stenosis induced by plaque rupture and superimposed thrombus is likely to improve or disappear with time and/or anticoagulant administration with/without antiplatelet therapy. Such information derived from CAG may improve the understanding and suggest optimal therapeutic strategies of coronary artery disease for individual patients.

Coronary Angiography↗

Stress technetium-99m tetrofosmin myocardial scintigraphy: a new one-hour protocol for the detection of coronary artery disease.

A one-hour protocol for stress myocardial scintigraphy using technetium-99m (99mTc) tetrofosmin was compared with scintigraphy using thallium-201 (201Tl) for the detection of coronary artery disease in 43 consecutive patients who underwent stress 201Tl and 99mTc-tetrofosmin myocardial scintigraphy, and coronary arteriography within 1 week. For the stress 99mTc-tetrofosmin test, rest imaging data were acquired 20 min after intravenous injection of 5-7 mCi 99mTc-tetrofosmin, using a 3-head gamma camera collecting 20-sec views over 360 degrees. After dobutamine infusion or bicycle ergometer exercise, 20-25 mCi of 99mTc-tetrofosmin was additionally injected at peak stress. The stress images were acquired 15 min after the second injection with 5-sec views over 360 degrees. All patients also underwent 201Tl exercise and redistribution (4-hour) imaging following a standard protocol. The overall sensitivity for detecting coronary artery disease was 96.0%, with an overall specificity of 93.3% for both types of scintigraphy. Qualitative analyses of 21 conventionally divided left ventricular segments showed that the overall segmental concordance between the 99mTc-tetrofosmin and 201Tl imagings was 85.2% on the rest images and 82.1% on the stress images. The segmental concordance of the rest images was 87.0% in patients with neither significant stenosis nor myocardial infarction, 86.2% in patients with significant stenosis without myocardial infarction, and 82.9% in patients with significant stenosis and myocardial infarction, and the concordance values of the stress images were 85.4%, 87.5% and 75.6%, respectively. These preliminary results suggest that stress myocardial scintigraphy using the present new protocol is a promising approach for the detection of coronary artery disease, with diagnostic sensitivity and specificity comparable to those of stress 201Tl scintigraphy.

Coronary Angiography↗

Purification and characterization of PAMP-12 (PAMP[9-20]) in porcine adrenal medulla as a major endogenous biologically active peptide.

Proadrenomedullin N-terminal 20 peptide (PAMP-20) is a potent hypotensive peptide processed from the adrenomedullin (AM) precursor. We developed a specific radioimmunoassay which recognizes the C-terminal region of PAMP-20. Using this radioimmunoassay, the distribution of immunoreactive (ir-) PAMP was determined in porcine tissues. High concentrations of ir-PAMP were observed in the adrenal medulla and in the atrium, and these values were comparable to the corresponding concentrations of ir-AM. The concentration of ir-PAMP was almost the same as that of ir-AM in the kidney, while ir-PAMP was significantly lower than ir-AM in the ventricle, lung, and aorta. Reversed-phase high performance liquid chromatography in each porcine tissue sample revealed that two major peaks of ir-PAMP existed: one emerged at a position identical to that of authentic porcine PAMP-20; the other unknown peak was eluted earlier. The unknown peptide was purified to homogeneity from porcine adrenal medulla, and its complete amino acid sequence was determined. This peptide was found to be PAMP[9-20] with a C-terminal amide structure, and was named PAMP-12. Intravenous injections of PAMP-12 in anesthetized rats showed a significant hypotensive effect in a dose-dependent fashion, and the effect was comparable to that of PAMP-20. These data indicate that PAMP-12, a major component of ir-PAMP, is processed from the AM precursor, as is PAMP-20, and may participate in cardiovascular control.

Adrenal Medulla↗

Effect of chronically infused adrenomedullin in two-kidney, one-clip hypertensive rats.

The hypotensive effect of chronically infused adrenomedullin, a potent vasodilator peptide, was examined in conscious two-kidney, one-clip (2K-1C) hypertensive and sham-operated rats. They were infused with 1.0 microgram/h of synthetic human adrenomedullin for 14 days by means of osmotic minipumps. Control groups were infused on the same schedule with 0.9% saline. Systolic blood pressure was measured before and during the infusion. Plasma renin activity, aldosterone and human adrenomedullin concentrations were determined at day 14 of the infusion. A significant reduction of systolic blood pressure was observed in the adrenomedullin-infused 2K-1C rats at day 4, and systolic blood pressure remained significantly lower throughout the experiment compared to that of the control 2K-1C. A similar hypotensive effect was seen in the adrenomedullin-infused sham-operated rats. Both the plasma renin activity and aldosterone concentrations of the adrenomedullin-infused 2K-1C and sham groups were significantly reduced compared to those of the respective control, whereas, the plasma human adrenomedullin concentration in the adrenomedullin-infused groups was found to be within the physiological range. These findings demonstrated that chronically infused adrenomedullin had a hypotensive effect accompanied by significant reductions of plasma renin activity and plasma aldosterone concentration in 2K-1C hypertensive and sham-operated rats.

Adrenomedullin↗

Plasma levels of adrenomedullin in primary and secondary pulmonary hypertension in patients <20 years of age.

To elucidate the pathophysiologic significance of adrenomedullin in pulmonary hypertension, we measured plasma adrenomedullin-like immunoreactivity (AM-LI) concentrations in blood samples obtained from various sites during cardiac catheterization by using radioimmunoassay in patients with pulmonary hypertension in comparison with patients without pulmonary hypertension. In patients with pulmonary hypertension, plasma AM-LI concentrations were significantly elevated and there was a significant uptake of AM-LI in pulmonary circulation, indicating the involvement of adrenomedullin in the cardiovascular regulation of pulmonary circulation in pulmonary hypertension.

Adolescent↗

Use of iodine-123 metaiodobenzylguanidine myocardial imaging to predict the effectiveness of beta-blocker therapy in patients with dilated cardiomyopathy.

It is crucial to predict drug effectiveness in chronic disease, such as dilated cardiomyopathy (DCM), in which the left ventricular (LV) function might be improved by beta-blocker therapy. As the functional improvement effected by beta-blocker therapy takes more than 2 months, we investigated whether iodine-123 metaiodobenzylguanidine (123I-MIBG) imaging could be used to predict drug effectiveness. We studied 13 patients (11 men and two women; mean age, 43+/-13 years) with DCM and seven normal subjects (six men and one woman; mean age, 48+/-16 years). We obtained myocardial single-photon emission tomography (SPET) images 15 min and 4 h after administration of 123I-MIBG (111 MBq). Studies were performed in the patients with DCM before and 1 and 3 months after the administration of metoprolol and in the normal subjects. We calculated the regional 123I-MIBG washout rate (r-WR) in the SPET image, and the global 123I-MIBG washout rate (g-WR) and heart-mediastinum activity ratio (H/M) using the anterior planar image. We classified patients into those showing a >/=5% increase in LV ejection fraction (LVEF) at 3 months compared with LVEF values before the treatment (group I, n=7) and those showing a <5% increase in LVEF (group II, n=6). In group I, the r-WR values at pretreatment and at 1 month and 3 months of treatment, respectively, were 36%+/-19%, 29%+/-14%* and 25%+/-13%* in the anterior segment, 39%+/-17%, 33%+/- 17%** and 28%+/-17%* in the lateral segment, 36%+/- 16%, 31%+/-14%* and 22%+/-12%** in the septal segment and 40%+/-11%, 37%+/-19% and 31%+/-18%* in the inferior segment; the g-WR was 45%+/-11%, 43%+/-10% and 34%+/-9%*, respectively (* P<0.05, ** P<0.01 vs pretreatment). In group II, there were no significant changes in regional or global parameters during the 3-month period. In normal subjects, the r-WR values in each of the anterior, lateral, septal and inferior segments were significantly lower than those in groups I and II. These values were 18%+/-9%, 18%+/-15%, 20%+/-12% and 21%+/-15%, respectively. This study demonstrated that with regional assessment 123I-MIBG SPET imaging can be used to predict the functional improvement of LVEF at 1 month of beta-blocker therapy in patients with DCM.

3-Iodobenzylguanidine↗

Effect of (-)-epigallocatechin gallate on leukemic blast cells from patients with acute myeloblastic leukemia.

Information on the anti-carcinogenic effect of EGCG, the main constituent of the polyphenols present in Japanese green tea leaves, has recently been accumulating. In this report, we evaluate the effect of EGCG on leukemic blast cells from AML patients. The results showed that EGCG inhibited the proliferation of AML cells in all cases examined. Since AML cells might proliferate by autocrine or paracrine growth mechanisms, we also examined the effect of EGCG on the production of GM-CSF from AML cells. Although EGCG did not directly inhibit the production of GM-CSF, it did inhibit the effect of TNF-alpha or TPA, both of which stimulated AML cells to produce GM-CSF. On the other hand, the modulation of receptors for growth factors might play a role in the proliferation or carcinogenesis of AML cells. We also found that EGCG inhibited the modulation of c-kit, a receptor for stem cell factor, on leukemic cells. These findings suggested that EGCG might be available as a new therapeutic tool for AML patients.

Blast Crisis↗

Production of adrenomedullin in human vascular endothelial cells.

To examine the production of adrenomedullin (AM) in human vascular endothelial cells, AM concentrations in cultured endothelial cells derived from the human umbilical vein and the conditioned media of the cells were measured in the present study. The cultured endothelial cells secreted immunoreactive AM (ir-AM) into the medium at a rate of 14.7 +/- 3.0 fmol/10(6) cells/24 h with an intracellular ir-AM of 5.2 +/- 0.8 fmol/l0(6) cells. Analysis by reverse phase high performance-liquid chromatography (HPLC) showed that ir-AM in both the cells and the conditioned medium eluted at the position identical to that of human AM(1-52). Treatment with dexamethasone significantly augmented the secretion of ir-AM from the cells without any effect on the intracellular ir-AM concentration. Northern blot analysis showed not only the presence of the 1.6 kb human AM precursor mRNA in the endothelial cells, but also its increased expression in the dexamethasone-treated cells. Thus, AM was synthesized and secreted by the human endothelial cells of the umbilical vein, and glucocorticoid augmented the AM production. These findings suggest not only the role of AM as a local modulator of the vascular tone but also the possibility that endothelial cells contribute to circulating AM in the human blood.

Adrenomedullin↗

Granulocyte colony-stimulating factor-combined marrow-ablative chemotherapy and autologous blood cell transplantation for the treatment of patients with acute myelogenous leukemia in first remission. The Fukouka Bone Marrow Transplant Group.

We conducted a clinical trial to increase the chemosensitivity of residual leukemic cells by combining G-CSF to marrow-ablative chemotherapy, including cytosine arabinoside (Ara-C), and facilitated by autologous blood cell transplantation (ABCT) for treatment of acute myelogenous leukemia (AML) in first complete remission. A total of 16 patients were consecutively treated with granulocyte colony-stimulating factor (G-CSF)-combined high-dose chemotherapy (busulfan, etoposide and Ara-C) followed by autotransplantation of peripheral blood progenitor cells, which had been collected after the consolidation chemotherapy. At a median follow-up time of 44.5 months, the probability of 5-year event-free survival was 74.5% with only three leukemic relapses. This preliminary observation suggests the effectiveness of G-CSF-combined conditioning and ABCT as a post-remission therapy for AML.

Adolescent↗

Urine and plasma levels of uroguanylin and its molecular forms in renal diseases.

Uroguanylin activates the intestinal and possibly the renal guanylate cyclase C receptor, and stimulates Cl- secretion. We developed a sensitive radioimmunoassay (RIA) for human uroguanylin and measured its concentration in the urine and plasma. Twenty-four-hour urinary excretion of immunoreactive (ir-) uroguanylin for persons with a high-salt diet (10 g/day) was 137.8 +/- 14.4 pmol/day, significantly higher than that for persons with a low-salt diet (7 g/day, 95.1 +/- 16.3 pmol/day, P < 0.05). There were significantly positive correlations between the urinary excretion of ir-uroguanylin and Na+, Cl-, K+ or cyclic GMP (cGMP). We demonstrated the presence of messenger RNA of guanylate cyclase C in the medulla of human kidney. The concentration of plasma ir-uroguanylin significantly correlated with that of serum creatinine (r = 0.71, P < 0.001). Biologically active uroguanylin-16 accounted for 99% of the endogenous uroguanylin molecules in normal urine and 60% in plasma, the remainder being the 10 kDa precursor. The precursor content increased in the urine and plasma as the severity of renal impairment increased. These findings suggest that bioactive uroguanylin-16 is involved in the regulation of electrolyte homeostasis and that the kidney participates in the metabolism and excretion of uroguanylin.

Circadian Rhythm↗

Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group.

Cytomegalovirus (CMV) infection and CMV-associated disease were monitored using the CMV antigenemia assay in 72 patients who received allogeneic bone marrow transplantation (BMT), and their incidences were compared between related and unrelated donor transplant patients. The incidence of CMV infection after BMT was significantly higher in patients who received transplants from HLA-matched unrelated donors than from HLA-matched sibling donors (87% vs 53%, P < 0.05). CMV-associated disease developed in 73% of unrelated and in 14% of sibling donor transplant patients (P < 0.01). The peak levels of CMV antigenemia were significantly higher in unrelated donors than in sibling donor transplant patients (16 vs 1 CMV antigen-positive cells per 50000 WBCs, P < 0.01). The median number of CMV antigen-positive cells on first detection was also significantly higher in unrelated donor transplant patients (15 vs 1, P < 0.01). The detection of CMV antigen-positive cells preceded the development of CMV-associated disease in 18% of unrelated donor transplant patients, suggesting a lower predictive value of CMV antigenemia for subsequent CMV-associated disease in unrelated donor BMT. Careful monitoring and further studies are needed for the early diagnosis and prevention of CMV-associated disease in unrelated donor BMT.

Adolescent↗

The effects of a simplified method for cryopreservation and thawing procedures on peripheral blood stem cells.

A simplified method for cryopreservation at -80 degrees C of peripheral blood stem cells (PBSC) has been increasingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has several advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is known about effects of long-term cryopreservation for years and thawing process on hematopoietic progenitors. We examined the recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the simplified method under various conditions as follows: (1) long-term storage for 1-5 years; (2) DMSO exposure for 1 h after rapid thawing; and (3) thawing at a lower temperature other than 37 degrees C. In our study, we found that the recovery rates of BFU-E and CFU-GM were not affected by the length of cryopreservation period; they remained at more than 70% on average for 16-61 months. In our hands, a 1-h exposure to DMSO after rapid thawing was not toxic for hematopoietic progenitors. Furthermore, there was no significant difference in the recovery rates of BFU-E and CFU-GM between thawing at 37 degrees C and 20 degrees C. These observations indicate that PBSC cryopreserved for at least 5 years by the simplified method can be used clinically without losing hematopoietic activity, and suggest that hematopoietic activity of the thawed PBSC may be unaffected when PBSC are infused slowly within 60 min or even when PBSC are thawed gradually at room temperature.

Blood Preservation↗

Autologous peripheral blood stem cell transplantation for acute myelogenous leukemia.

The safety and efficacy of myeloablative therapy followed by autologous peripheral blood stem cell transplantation (ABSCT) for acute myelogenous leukemia (AML) were evaluated in 60 patients. Peripheral blood stem cells (PBSC) were collected during recovery after consolidation chemotherapy. High-dose chemotherapy consisting of busulfan (16 mg/kg), etoposide (40 mg/kg), and cytosine arabinoside (3 g/m2 x 4) (BEA regimen) was used for pretransplant conditioning in 13 patients. For the remaining 47 patients, granulocyte colony-stimulating factor (G-CSF) was administered concurrently with the BEA regimen during conditioning. Unpurged, cryopreserved PBSC containing a median number of 5.4 x 10(8) MNC/kg or 12 x 10(4) CFU-GM/kg were reinfused at transplantation. The median number of days to granulocytes exceeding 500/microl and last platelet transfusion were 15 (8-44) and 24 (0->180), respectively. The 3-year probabilities of disease-free survival (DFS) and relapse were 78.6 and 21.4% for patients transplanted in first remission, 29.6 and 64.4% for those in second or third remission, and 11.1 and 77.8% for those in relapse, respectively. There were no transplant-related deaths within 100 days of transplantation. Age, disease status at transplantation, and number of induction chemotherapies to first complete remission were risk factors affecting the outcome of ABSCT. These results of ABSCT for AML in first remission warrant a prospective study of ABSCT as post-remission therapy.

Acute Disease↗