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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 271 records · Page 15Linked to original sources

[Evaluation of the invasion of esophageal cancer to the aorta by cine-MR imaging].

We examined the usefulness of cine-MR imaging for evaluation of the invasion of esophageal cancer to the aorta in 12 cases. We used the technique of field echo pulse sequence. When the low intensity stripe was recognized between the tumor and the wall of aorta, we interpreted it as negative finding of the direct tumor invasion. By using this criteria, 11 of the 12 cases (92%) of the esophageal cancer for aortic wall invasion were correctly diagnosed as compared with 75% correct diagnosis by conventional MR imaging.

Aorta

Preparation of anti-phosphoserine and anti-phosphothreonine antibodies and their application in the study of insulin- and EGF-induced phosphorylation.

We prepared antibodies against phosphoserine (P-Ser) and phosphothreonine (P-Thr) by immunizing rabbits with P-Ser or P-Thr conjugated to bovine serum albumin. The antibodies (anti-P-Ser and anti-P-Thr) were purified using P-Ser or P-Thr affinity columns. Anti-P-Thr was highly specific for P-Thr, while anti-P-Ser showed weak cross-reactivity with P-Thr. We showed that these antibodies can immunodetect serine/threonine phosphorylated insulin and epidermal growth factor (EGF) receptors and several proteins which are phosphorylated on serine/threonine residues in response to insulin or EGF stimulation. The antibodies will certainly provide a good tool for discovering novel kinases and substrates involved in signal transduction.

Animals

Somatic diversification and affinity maturation of IgM and IgG anti-DNA antibodies in murine lupus.

Molecular events occurring during the process of generation of pathogenic immunoglobulin (Ig)G anti-DNA antibodies in systemic lupus erythematosus (SLE) were studied using a newly established method. We analyzed the Ig variable (V) region gene sequence and DNA-binding activity of IgM and IgG anti-DNA monoclonal antibodies (mAb) from individual SLE-prone (NZB x NZW) F1 mice. The first event appeared to be clonal selection and expansion of IgM anti-DNA clones, in which several clones had intraclonal V gene mutations. Although the number of mutations was small, the mutated IgM clones were associated with an increase in DNA-binding activity. The somatic mutations located in complementarity-determining regions (CDR) and in framework regions (FR) of V genes were apparently related to changes in DNA-binding activity. IgG anti-DNA clones that progressively increased in number with aging had numerous somatic mutations in the V region genes and there was a pair of clones which showed an intraclonal accumulation of mutations, in association with increase in the DNA-binding activity. All these findings show that somatic mutations associated with affinity maturation of the V region begin immediately before isotype-switching from IgM to IgG of the clones that have been selected and expanded, in an antigen-driven manner and/or by other forces. We propose that further accumulations of intraclonal somatic hypermutation, in association with selection and expansion of high affinity IgG clones, may lead to formation of highly pathogenic anti-DNA antibodies.

Age Factors

Reduced renal arterial perfusion pressure stimulates renin release from domestic fowl kidneys.

Systemic hypovolemia and hypotension increase plasma renin activity (PRA) in fowl, but it is not clear whether this response is mediated directly by reduced renal arterial perfusion pressure (RAPP) or indirectly via renal nerves activated when systemic baroreceptors detect hypotension. To evaluate the influence of RAPP on renin release, arterial and renal venous blood samples were collected as RAPP was reduced step-wise from 108 mm Hg (control) to 71 and 47 mm Hg. PRA in systemic arterial (aPRA) and renal venous (vPRA) plasma was measured as the rate of fowl angiotensin I (ANG I) generation. Basal vPRA (2.47 +/- 0.6 ng x ml-1 x min-1) tended to be higher than aPRA (1.24 +/- 0.3 ng x ml-1 x min-1). When RAPP was reduced to 47 mm Hg both vPRA (4.35 +/- 0.6 ng x ml-1 x min-1) and aPRA (1.91 +/- 0.3 ng x ml-1 x min-1) increased significantly. Significant negative slopes (P = 0.01) were obtained when changes in aPRA or vPRA were regressed on RAPP. Mean systemic arterial pressure did not change during reductions in RAPP, nor did angiotensinogen concentrations differ when systemic arterial (472 +/- 30 ng/ml) and renal venous (460 +/- 27 ng/ml) plasma values were compared. Renal plasma flow was fully autoregulated as RAPP was reduced from 108 to 47 mm Hg; consequently, RAPP-induced increases in vPRA cannot be attributed to hemoconcentration of secreted renin. These results demonstrate that reductions in RAPP directly stimulate renin release from domestic fowl kidneys.

Angiotensin I

Aberrant retrotracheal goiter: report of a case.

A case of intrathoracic retrotracheal goiter in a 40-year-old woman is herein described. A computed tomographic scan, magnetic resonance imaging and endoscopical ultrasonography all confirmed the existence of a retrotracheal encapsulated lesion, which was suspected to be aberrant mediastinal goiter. Radioiodine scintigraphy, however, demonstrated little uptake in the mass. A large (7 x 6 x 4 cm), encapsulated adenomatous goiter was then easily removed via a right thoracic approach.

Adult

Primary squamous cell carcinoma of the breast in a pregnant woman: report of a case.

Although reports on primary squamous cell carcinoma of the breast have been increasing in number, the morbidity rate of the disease is comparatively low. Its onset in pregnant women, especially, is quite rare. We herein report a case of primary squamous cell carcinoma of the breast in a pregnant woman. A 33-year-old woman was admitted with a lump in the right breast and an abnormal bloody nipple discharge. The breast mass was 5.6 x 5.4 cm in size, and both ultrasonogram and CT scanning showed that it consisted of a cystic tumor for the most part. A large amount of bloody cystic fluid was aspirated by fine-needle aspiration; squamous cell carcinoma of the breast was suspected by a cytological study on the fluid. Twelve days after an induced abortion was performed, a modified radical mastectomy was carried out. Histological findings of the resected specimen demonstrated that the tumor was squamous cell carcinoma which had been well differentiated with partial keratinization and cancer pearls. Noninvasive ductal carcinoma was also observed in a very small region of the specimen, which indicated that the tumor was probably originally adenocarcinoma which later transformed into squamous cell carcinoma.

Adult

Cardiopulmonary function after pulmonary lobectomy in patients with lung cancer.

The effects of pulmonary lobectomy on cardiopulmonary function were investigated in 9 patients with lung cancer. Hemodynamic studies at rest and during exercise were performed before and 4 to 6 months after the operation. Differences in hemodynamics between before and after operation were observed with respect to heart rate, pulmonary arterial pressure, pulmonary vascular resistance index, and stroke volume index. Heart rate, pulmonary arterial pressure, and pulmonary vascular resistance index were significantly increased after operation, whereas stroke volume index was significantly decreased. It is thought that cardiac index was preserved by the increase in heart rate despite a decrease in stroke volume index associated with the decreased pulmonary vascular bed after the operation. When driving pressure and cardiac index were studied after operation, the pressure at rest and during exercise was higher, and the pressure-flow curve increased more steeply, as compared with the preoperative values. These results suggest a significant deterioration in cardiopulmonary function after lobectomy. As the patient characteristics were heterogeneous (five lobectomies and four bilobectomies), and their findings are limited, additional studies may be necessary in the future.

Aged

Atypical anxiolytic profile of buspirone and a related drug, SM-3997, in a modified forced swim test employing straw suspension.

Previous reports have shown that immobility time increases in the presence of suspended straws in association with an inhibition of straw-climbing behavior after acute administration of a prototypical anxiolytic benzodiazepine (BZD) such as diazepam. In this modified forced swim (MFS) test employing straw suspension, the effects of two new non-BZD compounds were tested and compared with those of diazepam (0.5, 1, and 5 mg/kg, IP) used in a previous MFS test. After a 5-min test of forced swimming, four straws were suspended just above the surface of the water and subsequently the straw-climbing trials were counted for 5 min as an index of escape behaviors induced by negative emotionality (stress and/or anxiety). Rats were injected IP with either saline, buspirone HCl (0.5, 1, and 5 mg/kg), or a related compound, SM-3997 (5, 10, and 20 mg/kg), 30 min before testing. At lower doses, both buspirone (0.5, 1 mg/kg) and SM-3997 (5, 10 mg/kg) reduced the duration of immobility, as opposed to that of diazepam. Conversely, buspirone at the highest dose of 5 mg/kg significantly prolonged the duration of immobility, and SM-3997 at 20 mg/kg also prolonged its duration, indicating a biphasic effects. All doses of buspirone and SM-3997 inhibited straw-climbing counts, in the same manner as diazepam. These results suggest that buspirone may possess relatively weak and/or atypical anxiolytic effects at lower doses, whereas at 5 mg/kg this compound may have an anxiolytic effect. In addition, SM-3997 may be a less potent anxiolytic drug than buspirone in the MFS test following a single-injection protocol.

Animals

Ampicillin concentrations in radicular cysts following a single oral administration of bacampicillin.

1. Ampicillin concentrations in cyst wall (wall) and cyst fluid (fluid) of radicular cyst and serum following a single oral administration of bacampicillin (equivalent to 500 mg of ampicillin) were measured by a paper disk method. 2. The mean peak concentrations of ampicillin in wall, fluid, and serum occurred at identical times, 1.5 hr, and were 2.39 micrograms/g, 0.77, and 10.24 micrograms/ml, respectively. 3. Mean ampicillin concentration ratios of wall/serum, fluid/serum, and fluid/wall at the peak time were 0.23, 0.07, and 0.40, respectively. 4. Mean ampicillin concentrations in wall and fluid at the peak time exceeded MIC (minimum inhibitory concentration) for 90% (0.5 microgram/ml) for clinically isolated strains of alpha-hemolytic Streptococci.

Administration, Oral

Haemodynamic and neurohumoral changes in spontaneously hypertensive rats with aortocaval fistulae.

1. Our aim was to evaluate the effects of an aortocaval fistula (1 mm) on cardiorenal haemodynamics, cardiac hypertrophy and neurohumoral factors in spontaneously hypertensive rats and to compare the results with those observed in Wistar rats at 2 weeks after fistulae placement. Sham-operated spontaneously hypertensive rats and Wistar rats served as controls. 2. Heart weight was significantly increased in spontaneously hypertensive rats (34%) and in Wistar rats (43%) at 2 weeks after fistula creation. Left ventricular systolic pressure and dp/dtmax. were significantly decreased (both P < 0.01) in spontaneously hypertensive rats with fistulae which had higher left ventricular end-diastolic pressure than Wistar rats with fistulae (P < 0.01). Signs of circulatory congestion (ascites, tachypnoea, prostration) were observed only in the overloaded spontaneously hypertensive rats (45%). Cardiac index was comparably increased in both fistulae groups due to an increase in stroke index, since heart rate was not increased. 3. Fistulae placement decreased renal blood flow and kidney weight, and increased blood urea nitrogen to a greater degree in spontaneously hypertensive rats (all P < 0.05); serum creatinine levels were unaltered. Plasma noradrenaline concentration was increased in spontaneously hypertensive rats with fistulae (P < 0.05), whereas plasma renin activity was not changed. 4. Thus, spontaneously hypertensive rats with fistulae developed overt haemodynamic signs of high-output heart failure with frequent ascites and dyspnoea, whereas most of these findings were milder or absent in Wistar rats. This model provides an opportunity to evaluate the pathophysiological and pharmacological responses in high-output heart failure.

Animals

Statistical mechanical approach for predicting the transition to non-B DNA structures in supercoiled DNA.

Supercoiling causes global twist of DNA structure and the supercoiled state has wide influence on conformational transition. A statistical mechanical approach was made for prediction of the transition probability to non-B DNA structures under torsional stress. A conditional partition function was defined as the sum over all possible states of the DNA sequence with basepair 1 and basepair n being in B-form helix and a recurrence formula was developed which expressed the partition function for basepair n with those for less number of pairs. This new definition permits a quick enumeration of every configuration of secondary structures. Energetic parameters of all conformations concerned, involving B-form, interior loop, cruciform and Z-form, were included in the equation. The probability of transition to each non-B conformation could be derived from these conditional partition functions. For treatment of effects of superhelicity, supercoiling energy was considered, and a twist of each conformation was determined to minimize the supercoiling energy. As the twist itself affects the transition probability, the whole scheme of equations was solved by renormalization technique. The present method permits a simultaneous treatment of several types of conformations under a common torsional stress. A set of energetic parameters of DNA secondary structures has been chosen for calculation. Some DNA sequences were submitted to the calculation, and all the sequences that we submitted gave stable convergence. Some of them have been investigated the critical supercoil density for the transition to non-B DNA structures. Even though the reliability of the set of parameters was not enough, the prediction of secondary structure transition showed good agreement with reported observation. Hence, the present algorithm can estimate the probability of local conformational change of DNA under a given supercoil density, and also be employed to predict some specific sequences in which conformational change is sensitive to superhelicity.

Algorithms

Structural analysis of O-linked sugar chains in human blood clotting factor IX.

Type and structural analysis of O-linked sugar chains in human blood clotting factor IX was performed by the pyridylamination method developed for O-linked sugar chains [Kuraya, N. & Hase, S. (1992) J. Biochem. 112, 122-126]. O- and N-linked sugar chains were released with hydrazine, and then N-acetylated, followed by pyridylamination. The type of sugar chain was determined by reducing-end analysis of the pyridylaminated (PA-) sugar chains. Sugar chains with PA-GalNAc at the reducing terminal and that with PA-Fuc [Nishimura, H. et al. (1992) J. Biol. Chem. 267, 17520-17525] were obtained besides known sugar chains with PA-Glc from the Xyl-Glc-Ser type and those with PA-GlcNAc from asparagine-linked sugar chains. The sugar chains with PA-GalNAc were identified as mono- and disialyl Gal beta 1-3GalNAc by two-dimensional HPLC mapping. The structure of the sugar chain with PA-Fuc was Neu5Ac alpha 2-6Gal beta 1-4GlcNAc beta 1-3Fuc, as determined by exoglycosidase digestion, methylation analysis, and Smith degradation.

Carbohydrate Conformation

Construction of an antigenic map of the haemagglutinin-esterase protein of influenza C virus.

Four different antigenic sites (A-1, A-2, B-1, B-2) have been identified previously on the haemagglutinin-esterase (HE) glycoprotein of influenza C/Ann Arbor/1/50 virus with seven monoclonal antibodies (MAbs). In this study we produced 30 additional anti-HE MAbs, nine of which demonstrated at least one of the following activities: haemagglutination inhibition, receptor-destroying enzyme inhibition, haemolysis inhibition, and neutralization (group A). The remaining had none of these activities (group B). These antibodies, and those previously isolated, were used to construct a more complete antigenic map of the HE molecule. Operational and topological analyses showed that a minimum of nine non-overlapping or partially overlapping antigenic sites were present on the HE protein, five recognized by group A MAbs (A-1 to A-5) and four by group B (B-1 to B-4). Among these antigenic sites, site A-5 was unique in that MAbs to this site inhibited the receptor-destroying activity without influencing the receptor-binding activity, which supports the idea that the sites responsible for these two functions are separate. It was also found that several group B MAbs were cross-reactive with host cell antigens.

Antibodies, Monoclonal

H-2z homozygous New Zealand mice as a model for B-cell chronic lymphocytic leukemia: elevated bcl-2 expression in CD5 B cells at premalignant and malignant stages.

In New Zealand mice, the major histocompatibility complex (MHC) controls the development of both autoimmune disease and B cell chronic lymphocytic leukemia (B-CLL). While H-2d/H-2z heterozygosity acts as one major predisposing genetic element for autoimmune disease, H-2z/H-2z homozygosity acts as an element for B-CLL. In the H-2z/H-2z homozygotes, there was an age-dependent increase in frequencies of CD5 B cells in the blood and spleen, and such CD5 B cells showed oligoclonal to monoclonal expansion, giving rise to B-CLL. B-CLL cells from these mice had surface phenotypes typical of CD5 B lineage cells, and expressed high levels of proto-oncogene bcl-2. Elevated bcl-2 expression was also observed in premalignant B cells in the aged mice, thereby suggesting that apoptosis-resistant, long-surviving CD5 B cells with a self-renewal capacity form the basis of malignant transformation. This model not only provides clues for analyzing multiple steps of genetic alterations involved in the generation of B-CLL, but also sheds light on the correlation between B-CLL and autoimmune disease.

Animals

Effects of prolonged application of isoprenaline on intracellular free magnesium concentration in isolated heart of rat.

1. The effect of prolonged application of isoprenaline on intracellular free-Mg2+ concentration ([Mg2+]i) was examined by use of 31P-nuclear magnetic resonance (31P-n.m.r.) in rat isolated hearts. Left ventricular pressure (LVP) was simultaneously measured. 2. [Mg2+]i was estimated from the separation of the alpha- and beta-ATP peaks, using the dissociation constant of MgATP 38 microM (established previously). In normal (phosphate-free, Krebs-Henseleit) solution, [Mg2+]i was approximately 0.4 mM. 3. When isoprenaline was applied for 100 min, a transient increase in [Mg2+]i was observed during the initial 25 min, whilst concentrations of ATP ([ATP]) and phosphocreatine ([PCr]) decreased and [Pi] correspondingly increased. During the subsequent 75 min of isoprenaline application, [Mg2+]i decreased below its resting levels. Washout of isoprenaline restored [Mg2+]i and [PCr], but [ATP] remained low. These changes elicited by isoprenaline were not observed in the presence of propranolol, a typical alpha-adrenoceptor blocker. 4. Isoprenaline increased both LVP and heart rate. The increased LVP and heart rate slowly returned to lower values during prolonged application of isoprenaline, but remained higher than those before application. 5. The transient rise in [Mg2+]i elicited by isoprenaline could be attributed to the decrease in [ATP] resulting in a release of Mg2+. The subsequent decrease in [Mg2+]i during the prolonged applications suggests that beta-adrenoceptor stimulation itself facilitates Mg(2+)-extruding mechanism(s).

Adenosine Triphosphate

Angiotensin II-induced endothelium-dependent relaxation of fowl aorta.

In the domestic fowl, angiotensin II (ANG II) decreases blood pressure in vivo and causes endothelium-dependent relaxation of aortic smooth muscles in vitro. To characterize ANG II-induced vasorelaxation, we compared endothelium-dependent vasodilatory effects of [Asp1,Val5]-ANG II (fowl ANG II) and acetylcholine (ACh) with the endothelium-independent vasorelaxing effect of sodium nitroprusside (SNP) on isometric tension of fowl aortic rings. Hemoglobin (Hb), gossypol, and N omega-nitro-L-arginine methyl ester (L-NAME), inhibitors for endothelium-derived relaxing factor (EDRF) in mammalian blood vessels, partially inhibited vasorelaxation induced by ANG II and ACh in fowl. Hb also markedly attenuated SNP-induced vasorelaxation, but not 8-bromoguanosine 3',5'-cyclic monophosphate-induced relaxation. 3,4,5-Trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8) or the removal of Ca2+ from the bathing medium attenuated the ACh-induced relaxation but did not significantly reduce vasorelaxation induced by ANG II or SNP. In the zero Ca2+ medium, aortic rings showed tachyphylaxis to ACh, while ANG II caused tachyphylaxis regardless of the presence or absence of external Ca2+. Furthermore, pretreatment of the ring with a high dose of ACh abolished the vasorelaxation response to ANG II, suggesting that ACh and ANG II may share a common Ca2+ pool. Calmidazolium, a calmodulin antagonist, abolished the vasorelaxation induced by ANG II and ACh but not that by SNP. Comparison of the vasodilatory effects of several ANG II analogues on fowl aortic rings showed an approximate potency order of [Asp1,Val5]-ANG II = [Asp1,Ile5]-ANG II > [Asn1,Ile5]-ANG II = [Sar1,Ile5]-ANG II > [Val5]-ANG III.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine