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Biomedical subjects

M Nagano

Publications and source records attributed to M Nagano.

At least 91 records · Page 5Linked to original sources
PubMed1997

T-stem cell leukemia/lymphoma with both myeloid lineage conversion and T-specific delta recombination.

We evaluated retrospectively the clinical and biological characteristics of six patients with CD7+ early T-acute lymphoblastic leukemia and lymphoma (T-ALL/LBL) originating from prothymocyte stage I (pro-T I) or II cells. Patients exhibited mediastinal mass (five of six) and lymphoadenopathy (five of six) but without leukocytosis and circulating blast cells (six of six). All patients achieved a complete remission. All but one had a relapse with a transformation to the mixed type (triphenotype--three cases, biphenotype-two cases) including myeloid features in three patients. The altered phenotypes were myeloperoxidase (MPO)+ (three of five), CD13+ (four of five), CD33+ (three of five) and CD19+ (three of five). The difference for MPO-positivity were observed between the bone marrow (BM)- and lymph node (LN)-blast cells (three of three). On cytogenetic analysis, there is no common abnormality in these patients. Immunomolecular analysis revealed T-cell lineage specific delta gene rearrangements [D delta 2-J delta 1 (five of six) and V delta 1-J delta 1 (one of six)] in all cases. Furthermore, D delta 2-J delta 1 occurred even in the cases with the pro-T I phenotype. Rearrangements of TCR beta, gamma or immunoglobulin heavy chain genes occurred in three patients. The same rearranged band(s) appeared at both diagnosis and relapse, indicating the same originality of the pro-T leukemic cell clone (three of three). We suggest that this type of CD7+ early T-ALL/LBL was transformed from a pro-T I or II cell, such as T-stem cell leukemia/lymphoma, which is a subtype of CD7+ stem cell leukemia as defined by Kurtzberg et al. This study reveals that pro-T I and II cells might be capable of myeloid, T- and B-lymphoid differentiation, and T-cell lineage specific TCR delta recombination occurs.

Adult↗
PubMed1997

Different administration schedules of the same dose of 2,5-hexanedione influence the development of neuropathy and the toxicokinetics.

The same total dose (1.2 g/kg/week) of 2,5-hexanedione (2,5-HD) was administered subcutaneously at 100 mg/kg/12 hr, 200 mg/kg/24 hr, and 400 mg/kg/48 hr to three groups of Donryu rats. The peripheral neuropathy induced by 2,5-HD was confirmed by clinical observation every day, and neurophysiological measurements every 4 weeks. During the 15th week of this experiment, 2,5-HD concentrations in plasma 0.5 to 24 hours after injection were determined. It was found that the greater the dose of 2,5-HD per treatment injected, the earlier peripheral neuropathy developed. Toxicokinetic analysis showed that both the values of the area under the plasma concentration versus time curve and the half life of 2,5-HD were increased, but the excretion parameters (Ke) were decreased, in animals treated with 200 mg/kg/24 hr and 400 mg/kg/48 hr 2,5-HD.

Animals↗
PubMed1997

Anti-thrombotic effects and bleeding risk of AJvW-2, a monoclonal antibody against human von Willebrand factor.

1. A murine anti-human vWF monoclonal antibody, AJvW-2, was developed that inhibited the interaction between platelet glycoprotein Ib (GPIb) and von Willebrand factor (vWF) during the ristocetin- (IC50 = 0.7 +/- 0.1 microgram ml-1) and botrocetin- (IC50 = 1.8 +/- 0.3 microgram ml-1) induced aggregation of human platelets. 2. AJvW-2 inhibited the high shear stress (10.8 N m-2) induced aggregation of human platelets dose-dependently with an IC50 = 2.4 +/- 0.3 micrograms ml-1, but had no effect on low shear stress induced platelet aggregation (1.2 N m-2) up to 100 micrograms ml-1. 3. AJvW-2 also inhibited the high shear stress (5.0 N m-2) induced adhesion of human platelets to collagen I with the same efficacy (IC50 = 2.4 +/- 0.3 micrograms ml-1), but no effect at low shear conditions (1.5 N m-2). 4. AJvW-2 inhibited the botrocetin-induced aggregation of platelets from guinea-pig, rat, rabbit, dog and pig at the same concentration range as human platelets; it likewise also inhibited the high shear stress induced aggregation and adhesion to collagen I of guinea-pig platelets. 5. AJvW-2 prevented arterial thrombus formation in guinea-pigs at a dose of 100 micrograms kg-1 without prolonging the template bleeding time, whereas the GPIIb/IIIa antagonists lamifiban mediated inhibition of thrombosis at 1000 micrograms kg-1 was accompanied by a significant prolongation of the bleeding time. 6. These results suggest that AJvW-2 is a potent inhibitor of the GPIb-vWF interaction and a potential novel antithrombotic agent with lower bleeding risk than GPIIb/IIIa antagonists.

Animals↗
PubMed1997

Renal effects of an angiotensin II antagonist in stroke-prone spontaneously hypertensive rat.

We evaluated the renal effects of the new angiotensin II type 1 (AT ) receptor antagonist, HR 720, in the stroke-prone spontaneously hypertensive rat. Rats were treated with either vehicle, HR 720, MK-954 (a selective AT1 receptor antagonist) or enalapril for 6 weeks. Blood pressure was decreased to a similar extent by HR 720, MK-954 and enalapril (203 +/- 4, 202 +/- 5 and 190 +/- 4 vs. 247 +/- 4 mm Hg for control). Urinary protein secretion was also decreased (5.2 +/- 0.3, 5.3 +/- 0.2 and 5.5 +/- 0.6 vs. 25.2 +/- 4.6 mg/100g/24h). The glomerular hypertensive change was improved in each drug-treated group (2.0 +/- 0.2, 3.3 +/- 0.3 and 1.6 +/- 0.1 vs. 17.6 +/- 1.5%; p < 0.0001). These results show that, in addition to its antihypertensive effect, HR 720 has a beneficial effect on renal function.

Angiotensin I↗
PubMed1997

Converting enzyme inhibitor improves forearm reactive hyperemia in essential hypertension.

Endothelial function is known to be impaired in essential hypertensive patients. In this study, we examined whether antihypertensive drugs improve forearm vasodilatory response to reactive hyperemia in 26 patients with essential hypertension (62 +/- 2 years) without diabetes mellitus, hyperlipidemia, coronary heart disease, or cerebrovascular disease. Antihypertensive drugs were never given or were discontinued for at least 4 weeks before the study. Patients were treated with monotherapy of either temocapril (2 or 4 mg, n = 15) or amlodipine (2.5 or 5 mg, n = 11) for 6 months. Forearm blood flow was measured by strain-gauge plethysmography. Vasodilator response to the release of upper arm compression at 300 mm Hg for 5 minutes and to sublingual administration of nitroglycerin (0.3 mg) were assessed. Changes of forearm blood flow response to reactive hyperemia were significantly less in hypertensive patients (99 +/- 18%) than in age-matched normotensive control subjects (150 +/- 22%, P < .01, n = 39). Blood pressure (mm Hg) was similarly decreased by the treatment with temocapril (160 +/- 4/94 +/- 2 to 139 +/- 3/83 +/- 3, P < .001) or amlodipine (165 +/- 5/94 +/- 3 to 141 +/- 4/82 +/- 3, P < .001). Response to nitroglycerin was not changed by either drug. Forearm vasodilatory response to reactive hyperemia was improved by temocapril (102 +/- 20% to 168 +/- 25%, P < .01) but not by amlodipine (97 +/- 16% to 114 +/- 14%, NS). These results indicate that the treatment with the angiotensin-converting enzyme inhibitor temocapril improved forearm vasodilatory response to reactive hyperemia, suggesting its beneficial effect on endothelial function.

Aged↗
PubMed1997

Influence of aging on progression of cardiovascular complications associated with insulin resistance in patients with essential hypertension.

Hyperinsulinemia or insulin resistance is suggested to play a role in the pathogenesis of hypertension and its target organ diseases. It is also well documented that aging is associated with a decline in glucose tolerance and insulin sensitivity, but there are few reports on the relationship between aging and insulin sensitivity or on the effects of aging on the progression of cardiovascular complications in patients with essential hypertension. To clarify these effects of aging in essential hypertension, 44 patients were examined by the euglycemic hyperinsulinemic glucose clamp test and ultrasonography of the heart and carotid arteries. There was a significant negative correlation between aging and insulin sensitivity (r = -0.37, p < 0.05). Significant increases in left ventricular mass index and carotid wall thickening accompanied by insulin resistance were seen in only non-elderly patients but not in elderly patients. These results suggest that aging decreases insulin sensitivity even in essential hypertensive subjects and that insulin resistance does not affect the progression of cardiac hypertrophy and atherosclerosis in elderly patients with essential hypertension.

Aged↗
PubMed1997

[A case of asynchronous quadruple cancer arising from the prostate, stomach, rectum and urinary bladder].

Herein, we report a case of quadruple cancer arising from the prostate, stomach, rectum and urinary bladder. A 92-year-old man was admitted to our hospital on March, 1996, with complaints of macroscopic hematuria and micturition pain. He had a history of prostate cancer (no details) at the age of 67, and subtotal gastrectomy for gastric cancer (tubular adenocarcinoma, conclusive stage Ia) at the age of 89. He underwent a polypectomy for rectal cancer (well-differentiated adenocarcinoma)2 at the age of 90. There was no evidence of local recurrence or metastasis of these three carcinomas. Cystoscopy revealed multiple papillary tumors which were resected transurethrally. At the same time transrectal needle biopsy of prostate was performed. Pathology revealed transitional cell carcinoma G2 of urinary bladder and well differentiated adenocarcinoma of prostate. The postoperative course was uneventful and the patient has been doing well without recurrence of bladder cancer during the follow-up period of six months.

Adenocarcinoma↗
PubMed1996

High occurrence of primary malignant neoplasms in patients with adult T-cell leukemia/lymphoma, their siblings, and their mothers.

BACKGROUND: Attempts were made to clarify the correlation between human T-cell leukemia/lymphoma virus (HTLV)-1 infection and malignant oncogenicity other than adult T-cell leukemia/lymphoma (ATL) in a case-control study. METHODS: The occurrence of primary malignant neoplasms (MN) in 110 ATL patients, their parents, and 430 siblings was compared with HTLV-1 seronegative non-Hodgkin's lymphoma (NHL) patients, their parents and 867 siblings. The chi-square test, odds ratio (OR), and 95% confidence intervals (CI) were used to determine the statistical significance of differences in the occurrence of the primary MN among ATL patients, HTLV-1 seronegative NHL patients, their siblings, and their parents. RESULTS: The occurrence of primary MN in the ATL patients was higher than the occurrence in HTLV-1 seronegative NHL patients (P = 0.0036; OR = 2.91; 95% CI: 1.42, 6.02). In siblings of the ATL patients, there was a higher occurrence of primary MN than in siblings of the HTLV-1 seronegative NHL patients (P < 0.0001; OR = 3.35; 95% CI: 2.01, 5.58). In mothers of the ATL patients, there was a higher occurrence of primary MN than in mothers of the HTLV-1 seronegative NHL patients (P = 0.0063; OR = 2.55; 95% CI: 1.30, 5.00), but not in fathers (P = 0.1602; OR = 1.68; 95% CI: 0.81, 3.47). CONCLUSIONS: There is an increased risk of primary MN in ATL patients, their siblings, and their mothers.

Aged↗
PubMed1996

Cloning of Xenopus TFIIS and its expression in oocytes and early embryos.

The transcriptional factor TFIIS has been cloned from Xenopus laevis. The length of the cDNA is 1668bp and contains the complete open reading frame of 303 amino acids. Xenopus TFIIS has high homologies to its human and mouse counterparts. In Northern blot analyses, TFIIS mRNAs that consisted of four different sizes were expressed relatively highly from the early stages of Xenopus oogenesis. During oocyte maturation, the pattern of Xenopus TFIIS messages showed a transient peak of expression. TFIIS mRNA occurred maternally and its level increased in later stage embryos. These data suggest that TFIIS mRNA is expressed in a developmentally regulated way in Xenopus laevis.

Amino Acid Sequence↗
PubMed1996

Hemorrhage from abdominal non-Hodgkin's lymphoma treated successfully by emergency transcatheter arterial embolization.

A 49-year-old Japanese woman with follicular lymphoma who presented with severe abdominal and back pain is reported. She was known to have malignant lymphoma and had been previously treated with combination chemotherapy. An abdominal tumor occurring at the root of the mesentery and involving the superior mesenteric artery (SMA) had been diagnosed by computed tomography (CT), magnetic resonance imaging, and abdominal angiography. Emergent ultrasonography and CT findings showed intraperitoneal bleeding from the abdominal tumor. Selective SMA angiography revealed extravasation from a small branch originating from the dorsal pancreatic artery, which was embolized through a catheter by using platinum coils. It should be noted that a large tumor of malignant lymphoma, involving large vessels, may bleed, and in such a case selective transcatheter arterial embolization may be one of the effective modalities for hemostasis.

Abdominal Neoplasms↗
PubMed1996

Bone bonding ability of an apatite-coated polymer produced using a biomimetic method: a mechanical and histological study in vivo.

A 20-microns thick apatite layer was coated onto polyethersulfone (PES) rectangular plates by soaking them in simulated body fluid containing CaO-SiO2 based glass powder. Coated and uncoated PES plates (10 x 15 x 1.5 mm) were implanted in the tibiae of rabbits, which were sacrificed 8, 16, and 30 weeks thereafter, and the samples were examined histologically using contact microradiography (CMR), Giemsa surface staining, and a scanning electron microscope connected to an electron probe microanalyzer (SEM-EPMA). The tensile failure loads at the bone/implant interfaces were determined using the detaching test. The histological examinations showed excellent bone apposition on coated PES and the sign of degradation of the apatite layer at remodeling lacunae. The apatite layer underwent complete resorption and was replaced by bone in most areas of the bone/implant interface after 30 weeks. Bone did not bond directly to uncoated PES after each follow-up period. The failure loads between bone and coated PES at 8, 16, and 30 weeks after implantation were 1.7 +/- 0.35, 2.36 +/- 0.53, and 1.45 +/- 0.48 kg, respectively. Those between bone and uncoated PES were nearly 0 kg at each postimplantation period. Failure during the detaching test occurred at the bone/apatite interface or near it after 8 weeks. After 16 weeks, it usually occurred at the apatite/ PES interface or near it, and occasionally in the middle of the apatite layer. The apatite layer was hardly detected at the failured interface after 30 weeks. In this study, an apatite-coated PES produced using a biomimetic method was demonstrated to bond directly to bone without any intervening soft tissue, which indicates that this material possesses excellent bioactivity.

Animals↗
PubMed1996

The effects of 2,5-hexanedione and acrylamide on myosin heavy chain isoforms of slow and fast skeletal muscles of the rat.

We examined the effects of 2,5-hexanedione (2,5-HD) and acrylamide (ACR) on the muscle fiber types and myosin heavy chain (MHC) isoform composition of the slow-twitch soleus and fast-twitch plantaris muscles of rats. We employed two differently designed experiments with respect to the dosage levels and treatment periods for developing clinical neuropathies. When male Wistar rats were subcutaneously injected with 4.5 mmol of 2,5-HD/kg or 0.4 mmol of ACR/kg, 5 days a week, they developed paralysis of the hindlimbs in 4 weeks (high-dosage experiment). When they were subcutaneously injected with 3.5 mmol of 2,5-HD/kg or 0.35 mmol of ACR/kg, 5 days a week, paralysis of the hindlimbs did not develop until 6 weeks (low-dosage experiment). We examined mainly the rats treated with the neurotoxicants for 4 and 8 weeks in the high-and low-dosage experiments, respectively. Significant decreases in the maximum motor conduction velocity of the sciatic nerves were observed in the hindlimbs of the rats in both experiments. The weights of the soleus and plantaris muscles were significantly reduced in the 2,5-HD-treated rats in both experiments, while in the ACR-treated rats, the weights of both muscles decreased only in the low-dosage experiment. We could not detect any changes in the fiber type composition of the muscles by any of the treatments. However, biochemical analysis revealed decreases in the values (percentage) of the relative amounts of fast-type MHC IIa and IIb isoforms to total MHC isoforms in the 2,5-HD-treated rats, but not in the ACR-treated rats in the high-dosage experiment. In contrast, significant differences in the relative amounts of MHC isoforms were not observed after administration of the low dosage of 2,5-HD. These results suggest that 2,5-HD preferentially disorders the muscle fibers which contain the MHC II isoform. These effects may occur only after the relatively acute intoxication of 2,5-HD at a high dosage.

Acrylamide↗
PubMed1996

Differences of bone bonding ability and degradation behaviour in vivo between amorphous calcium phosphate and highly crystalline hydroxyapatite coating.

Three types of calcium phosphate coating were formed on polyethersulphone (PES) rectangular plates using a biomimetic method: a 20 microns thick amorphous calcium phosphate (ACP 20) coating, a 50 microns thick amorphous calcium phosphate (ACP 50) coating, and a 50 microns thick highly crystalline hydroxyapatite (hHA 50) coating. Uncoated PES plates were used as a control group. These materials were implanted in the tibiae of rabbits and subcutaneously in rats, and the samples were harvested 8 and 16 weeks thereafter, and were examined histologically. The tensile failure loads at the bone-implant interfaces were determined using the detaching test. Each ACP coating was more degradable than the hHA 50 coating. However, newly formed bone came into direct contact with underlying materials as the coating degraded. No coating degraded in subcutaneous tissue. Soft tissue intervening was seen in uncoated samples. Failure load of ACP 20-, ACP 50- and hHA 50-coated samples were all relatively higher than that of the uncoated samples at each period. Significant increase of failure load was seen in hHA 50-coated samples by 16 weeks, however, no increase was seen in either the uncoated or ACP-coated samples. If coating longevity is desired, then the hHA coating is preferable. However, if only the osteoconducive property of calcium phosphate coating is desired for initial fixation of porous materials, the ACP coating may be advantageous.

Animals↗
PubMed1996

Ultrastructural study of an apatite layer formed by a biomimetic process and its bonding to bone.

A dense and uniform apatite layer about 20 microns thick was formed on a poly(ether sulphone) (PESF) substrate treated with glow discharge in O2 gas by a biomimetic process. The apatite-polymer composite obtained was implanted into a rabbit tibia and the structure of the PESF-apatite-bone interface was observed under a scanning and a transmission electron microscope 8 weeks after implantation. The apatite layer formed by the biomimetic process was confirmed to consist of small crystals of apatite with a structure similar to that of apatite in bone. The apatite layer remained on the substrate in the body, and bonded to the apatite in bone directly. This type of apatite-organic polymer composite expected to be useful as bone-repairing material.

Animals↗
PubMed1996

Predominance of nocturnal sympathetic nervous activity in salt-sensitive normotensive subjects.

To assess the relation between salt sensitivity and autonomic nervous function by power spectral analysis of heart rate variability in normotensive subjects, low and high salt diets were given to 13 normotensive men (aged 25 to 39 years) for 4 days each. Autonomic function was assessed by power spectral analysis of R-R intervals based on an autoregressive algorithm from 24-h Holter electrocardiogram. Subjects whose mean blood pressure was increased more than 3 mm Hg by high salt diet were defined as salt sensitive (SS, n = 5), and the remainder as salt resistant (SR, n = 8). Using the low frequency (LF, 0.1 Hz) and high frequency (HF, 0.25 Hz) components, the LF to total power ratio (%LF) was used as a marker of sympathetic activity, and the HF to total power ratio (%HF) as a marker of parasympathetic activity. Compared to the daytime, SR revealed a decrease in %LF and an increase in %HF during the night on both diets. In SS, these circadian changes were observed only during low-salt diet. During the night, SS showed a higher %LF and a lower %HF than SR. Plasma catecholamines tended to be decreased by the high sodium diet in SR but not in SS subjects. These results suggest that the persistent nocturnal predominance of sympathetic nervous activity in a salt-sensitive men may contribute to the subsequent increase of blood pressure in these subjects.

Adult↗
PubMed1996

Impaired endothelial function with essential hypertension assessed by ultrasonography.

The objective of this investigation was to evaluate the role of hypertension in endothelial function, changes in which are known to be an early event of atherosclerosis. We assessed endothelial function in 13 subjects with normal blood pressure and 13 subjects with essential hypertension who had never been treated for hypertension or hyperlipidemia and who had no history of smoking or coronary or cerebrovascular disease. B-mode ultrasonography was used to measure the diameter of the brachial artery. Endothelium-dependent dilatation was assessed as the change in diameter of the artery during reactive hyperemia. Endothelium-independent dilatation was evoked, as a control, by sublingual administration of isosorbide dinitrate. Despite similar ages and lipid and glucose levels in the study groups, endothelium-dependent dilatation was less in patients with hypertension (13.1% +/- 1.6%) than in subjects with normal blood pressure (18.5% +/- 1.9%) (p < 0.05), whereas isosorbide dinitrate-induced changes were similar. Systolic and diastolic blood pressure were significantly correlated with endothelium-dependent vasodilatation (r = -0.57 and r = -0.53, respectively) but not with the change by isosorbide dinitrate. These results suggest that endothelial dysfunction exists in patients with hypertension and precedes overt atherosclerotic disease.

Adult↗
PubMed1996

Insulin resistance and cardiovascular complications in patients with essential hypertension.

Hyperinsulinemia or insulin resistance is suggested to play a role in the pathogenesis of hypertension and its target organ diseases. We designed this study to evaluate the role of insulin resistance in cardiac function, cardiac hypertrophy, wall thickness of the common carotid artery, and endothelial function of the brachial artery in essential hypertensive patients without diabetes mellitus. Insulin resistance was evaluated by the constant glucose infusion rate (M value) during the euglycemic-hyperinsulinemic glucose clamp test. In correlation analysis for several indices of glucose metabolism, only M value correlated with left ventricular mass index (LVMI), ratio of peak velocity during atrial contraction to that during early left ventricular filling phase (E/A ratio) and intima-media complex (IMC). In stepwise regression analysis of various risk factors for cardiovascular diseases, only M value and age were dependent factors for LVMI, E/A ratio, and IMC. No indices of glucose metabolism or risk factors for cardiovascular diseases correlated with endothelium-dependent and -independent vasodilation. These results suggest that insulin resistance, but not glucose intolerance and hyperinsulinemia, partly accelerates cardiovascular complications such as left ventricular hypertrophy and wall thickening of the carotid artery in patients with essential hypertension.

Blood Flow Velocity↗