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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 433 records · Page 24Linked to original sources

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↗

Rescue of neuronal function by cross-regeneration of cutaneous afferents into muscle in cats.

1. This study investigates the relation between the peripheral innervation of low-threshold cutaneous afferents and the postsynaptic potentials elicited by electrical stimulation of those afferents. 2. In cats deeply anesthetized with pentobarbital sodium, cord dorsum potentials (CDPs) and postsynaptic potentials (PSPs) in spinal motoneurons were elicited by stimulation of the caudal cutaneous sural nerve (CCS), the lateral cutaneous sural nerve (LCS), and the medial gastrocnemius (MG) muscle nerve. We tested 1) unoperated cats, and cats in which CCS has been 2) chronically axotomized and ligated, 3) cut and self-reunited, 4) cut and cross-united with LCS, or 5) cut and cross-united with the MG. Terminal experiments were performed 3-36 mo after initial surgery. 3. In cats in which the CCS had been self-reunited or cross-united distally with LCS, tactile stimulation of the hairy skin normally innervated by the distal nerve activated afferents in the CCS central to the coaptation, indicating that former CCS afferents had regenerated into native or foreign skin, respectively. 4. In cats in which the CCS had been cross-united distally with the MG, both stretch and contraction of the MG muscle activated the former CCS afferents. 5. In unoperated cats, CDPs elicited by stimulation of CCS and of LCS exhibited a low-threshold N1 wave and a higher-threshold N2 wave. These waves were greatly delayed and appeared to merge after chronic axotomy of CCS. Regeneration of CCS into itself, into LCS, or into MG restored the normal latencies and configurations of these potentials. 6. In unoperated cats, stimulation of CCS, of LCS, and of MG each produced PSPs of characteristic configurations in the various subpopulations of motoneurons of the triceps surae. CDPs and PSPs elicited by the CCS cross-regenerated into LCS or MG were typical of those generated by the normal CCS, i.e., there was no evidence of respecification of central synaptic connections to bring accord between center and periphery after cross-regeneration. 7. Chronic axotomy of CCS increased the latencies of PSPs from CCS; regeneration of CCS into the CCS, LCS, or MG restored normal latencies. 8. In summary, CDPs and PSPs in motoneurons from the cutaneous sensory nerve CCS are altered by chronic axotomy of CCS, thus indicating their target dependency. These alterations are restored by regeneration of CCS into not only a native or foreign cutaneous target, but also into skeletal muscle. We conclude that muscle as well as skin is capable of providing trophic support for cutaneous afferents.

Afferent Pathways↗

Characterization of factors that suppress linear DNA replication in SV40 in vitro replication system.

The in vitro simian virus 40 (SV40) replication system has been developed as a model system of cellular DNA replication, because the replication initiated from the replication origin of SV40 and replication fork proceeds bidirectionally. In this system, SV40 T-antigen (TAg) is the only factor provided by viral genes, while all other factors are supplied by the host cells. A suppression of replication has been observed in the linear template containing SV40 replication origin, compared with the closed circular template in the SV40 in vitro replication system using a crude extract of HeLa cells. However in the in vitro replication system reconstituted from partially purified factors, less preference was observed for the replication of the closed circular DNA over the linear DNA. In a mono-polymerase system supplemented by crude extracts, a suppression of replication in a linear template was also observed, when compared with a closed circular template. This suppression effect of crude extract was abolished by heat treatment, suggesting that the suppression was induced by some protein factors. A crude extract of HeLa cells was fractionated by stepwise elution with buffers containing 0.2 M, 0.4 M, 0.6 M and 1 M NaCl on a phosphocellulose column, and characterization of factors that suppress linear DNA replication has been done. Both fractions that were eluted at 0.4 M and 0.6 M from phosphocellulose were necessary to suppress linear DNA replication efficiently. The factors in the 0.6 M fraction that suppressed linear DNA replication synergistically with the 0.4 M fraction were partially purified by successive chromatography with heparin-sepharose and dsDNA-cellulose followed by glycerol gradient centrifugation. These results suggested that multiple factors are required to suppress DNA replication of the linear template.

Cell Fractionation↗

Effects of renal denervation on pressure-natriuresis in spontaneously hypertensive rats.

To investigate the role of renal sympathetic nerve activity (RSNA) under developing and established hypertension, renal function was studied in chronically renal-denervated and sham-operated male spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats (WKY) at 8 (early hypertensive) and 22 (established hypertensive) weeks of age. To further characterize the renal pressure-natriuresis-diuresis relationship in SHR, renal perfusion pressure (RPP) was reduced by aortic constriction to the level seen in age-matched WKY and the same studies were repeated. After denervation, urinary sodium excretion (UNaV), fractional excretion of sodium (FENa) and urine flow (UF) were increased in 8-week-old SHR (p < 0.01). With the exceptions of UNaV and FENa in denervated 8-week-old SHR, renal cortical blood flow, glomerular filtration rate, UF, UNaV and FENa decreased with the reduction of RPP in all of the SHR groups. These results suggest that RSNA significantly influences renal sodium and fluid handling, thus contributing to the shifting of the arterial pressure-renal sodium excretion curve to the right along the pressure axis and/or to an increase in the steepness of the relationship in 8-week-old SHR. There appeared to be a marked difference in renal sodium handling between 8- and 22-week-old SHR.

Animals↗

Are diabetic hearts more resistant to ischemia/reperfusion injury?

The present study was designed to investigate the cardiac impairment during ischemia/reperfusion injury in rats with streptozotocin-induced diabetes vs controls. Male rats were divided into three groups: controls, one-week diabetic rats (1wDM) and four-week diabetic rats (4wDM). In the isolated working heart, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and maximum positive and negative dP/dt were measured before ischemia and after 20 min of global ischemia followed by 30 min reperfusion. In the pre-ischemic state, hearts of 4wDM showed a significant (p < 0.05) depression of the maximum positive and negative dP/dt compared with those of controls and 1wDM. There were no significant differences in LVDP and LVEDP among the three groups. The incidence of reperfusion-induced ventricular fibrillation (VF) was 75% for controls, 15% for 1wDM rats, and 27% for 4wDM rats. In hearts without reperfusion-induced VF, there were no differences in the three groups, between the pre- and post-ischemic values in LVDP, LVEDP, and maximum positive and negative dP/dt. These findings suggest that diabetic hearts exhibit no susceptibility to ischemia/reperfusion injury.

Animals↗

Hemodynamic and neurohumoral responses to exercise in patients with congestive heart failure.

Hemodynamic and neurohumoral responses to supine bicycle exercise were evaluated in 16 patients with congestive heart failure (New York Heart Association functional class II-III) and in 8 normal controls. We determined cardiac output by the dye-dilution method, and forearm hemodynamics by plethysmography. The patients had lower resting cardiac and stroke indexes (p < 0.05) than the normal controls. During exercise, the increase in the cardiac index due to an increase in heart rate, was less than that in the controls. Resting and exercise systemic vascular resistance indices were higher in the patients (p < 0.05). The patients had lower resting forearm blood flow and higher forearm vascular resistance (p < 0.05), and the increases during exercise were comparable in the 2 groups. However, forearm venous tone and venous pressure increased more in the patients (p < 0.05). Exercise duration was shorter in the patients (p < 0.01). Resting plasma angiotensin II and norepinephrine were similar in the 2 groups, but plasma 6-keto-prostaglandin F1 alpha and atrial natriuretic peptide were higher in the patients. During exercise, all of these neurohumoral parameters rose more in the patients than in the controls (p < 0.05). Thus, the patients exhibited impaired central and peripheral hemodynamics both at rest and during exercise. The excessive exercise responses of all of the neurohumoral factors suggest that both vasoconstrictor and vasodilator systems are activated in heart failure.

6-Ketoprostaglandin F1 alpha↗