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Biomedical subjects

H Asanuma

Publications and source records attributed to H Asanuma.

At least 19 recordsLinked to original sources
PubMed1999

Enhanced protection against a lethal influenza virus challenge by immunization with both hemagglutinin- and neuraminidase-expressing DNAs.

The ability of plasmid DNA encoding hemagglutinin (HA), neuraminidase (NA) or matrix protein (M1) from influenza virus A/PR/8/34 (PR8) (H1N1), and mixtures of these plasmid DNAs (HA + NA and HA + NA + M1) to protect against homologous or heterologous virus infection was examined in BALB/c mice. Each DNA was inoculated twice, 3 weeks apart, or four times, 2 weeks apart, at a dose of 1 microg of each component per mouse by particle-mediated DNA transfer to the epidermis (gene gun). Seven days after the last immunization, mice were challenged with a lethal homologous or heterologous virus and the ability of each DNA to protect the mice from influenza was evaluated by observing lung virus titers and survival rates. The administration of a plasmid DNA mixture of either (HA + NA) or (HA + NA + M1) provided almost complete protection against the PR8 virus challenge, and this protection was accompanied by high levels of specific antibody responses to the respective components. The degree of protection afforded in these groups is significantly higher than that in mice given either HA- or NA-expressing DNA alone, which provided only a partial protection against PR8 challenge or that in mice given M1-expressing DNA, which failed to provide any protection. In addition, both of the plasmid DNA mixtures (HA + NA) and (HA + NA + M1) showed a slight tendency to provide cross-protection against an A/Yamagata/120/86 (H1N1) virus challenge, and this was accompanied by a relatively high level of cross-reacting antibodies. Thus, there was no clear difference between the ability of the HA + NA and HA + NA + M1 plasmid DNA mixtures in providing protection against either a PR8 or heterologous virus challenge. These results suggest that in mice immunized by gene gun, a mixture of plasmid DNAs encoding HA and NA can provide the most effective protection against the virus challenge. The addition of the M -expressing plasmid DNA to this mixture does not enhance the degree of protection afforded.

Animals↗
PubMed1999

Plasma adenosine levels and platelet activation in patients with atrial fibrillation.

Platelet activation is observed in patients with atrial fibrillation (AF). P-selectin, which is expressed on platelet activation, plays an important role in the formation of thromboemobli. Because adenosine is known to attenuate platelet activation, we evaluated adenosine levels and 2 indicators of platelet activation, i.e., expression of P-selectin on platelets and plasma levels of beta-thromboglobulin, in 28 patients with AF (20 men and 8 women, age range 64+/-2 years) with sex- and age-matched (+/-2 years) subjects with sinus rhythm. The incidence of risk factors for stroke except for coronary heart disease and in echocardiographic parameters did not differ between the 2 groups. Plasma adenosine levels were lower (p <0.05) in patients with AF than in controls (mean [interquartile range] 13.4 [19.3-9.3] vs 19.1 [30.8-11.9] nmol/L). The expression of P-selectin on platelets (6.8% [13.6-3.4] vs 4.0% [8.8-1.8]) and plasma levels of beta-thromboglobulin were higher (p <0.05) in patients with AF. Flow cytometric analysis revealed that an antagonist of adenosine receptors, 8-sulfophenyltheophylline, increased the expression of P-selectin on platelets in a dose-dependent manner in the in vitro study. These results suggest that decreased plasma levels of adenosine were associated with platelet activation in patients with AF. Substitution of adenosine may provide a strategy for preventing platelet activation in these patients.

Adenosine↗
PubMed1999

A Ca channel blocker, benidipine, increases coronary blood flow and attenuates the severity of myocardial ischemia via NO-dependent mechanisms in dogs.

OBJECTIVES: This study was undertaken to examine whether a dihydropyridine Ca channel blocker, benidipine, increases cardiac NO levels, and thus coronary blood flow (CBF) in ischemic hearts. BACKGROUND: Benidipine protects endothelial cells against ischemia and reperfusion injury in hearts. METHODS AND RESULTS: In open chest dogs, coronary perfusion pressure (CPP) of the left anterior descending coronary artery was reduced so that CBF decreased to one-third of the control CBF, and thereafter CPP was maintained constant (103+/-8 to 42+/-1 mmHg). Both fractional shortening (FS: 6.1+/-1.0%) and lactate extraction ratio (LER: -41+/-4%) decreased. Ten minutes after the onset of an intracoronary infusion of benidipine (100 ng/kg/min), CBF increased from 32+/-1 to 48+/-4 ml/100g/ min during 20 min without changing CPP (42+/-2 mmHg). Both FS (10.7+/-1.2%) and LER (-16+/-4%) also increased. Benidipine increased cardiac NO levels (11+/-2 to 17+/-3 nmol/ml). The increases in CBF, FS, LER and cardiac NO levels due to benidipine were blunted by L-NAME. Benidipine increased cyclic GMP contents of the coronary artery of ischemic myocardium (139+/-13 to 208+/-15 fmol/mg protein), which was blunted by L-NAME. CONCLUSION: Thus, we conclude that benidipine mediates coronary vasodilation and improves myocardial ischemia through NO-cyclic GMP-dependent mechanisms.

Animals↗
PubMed1999

Glycoprotein IIb/IIIa antagonist FK633 could not prevent neointimal thickening in stent implantation model of canine coronary artery.

The platelet glycoprotein (GP) IIb/IIIa receptor antagonist appears to reduce the need for revascularization after coronary angioplasty. However, since the effect of GP IIb/IIIa receptor antagonist on the in-stent neointimal thickening has not been clarified, we examined it in the canine model. The beagle dogs were assigned to the control (n=7) or the GP IIb/IIIa receptor antagonist FK633 group (n=7). FK633 was administered by subcutaneous osmotic pumps (0.2 mg. kg-1. h-1) and an intravenous bolus injection (1 mg/kg) before stenting. A coil stent was implanted in the left circumflex coronary arteries. The platelet aggregation capability was significantly (<5%) and consistently reduced by FK633 except for the mild elevation (10% to 30%) on the next day of stenting. Hearts were excised 3 months after stent implantation. The area of intima and media and the area stenosis were obtained from the sections of the stented arteries. The area of intima and media and the area stenosis (1.3+/-0.2 mm2, 41.8+/-7.5% and 1.3+/-0.2 mm2, 33.9+/-6.7% in the FK633 and the control group, respectively) were not different between the groups. We conclude that, although GP IIb/IIIa antagonist FK633 prevented the platelet aggregation significantly and consistently, it could not prevent the neointimal thickening after stent implantation in canine coronary artery.

Animals↗
PubMed1998

Detection of cytokines and cytomegalovirus DNA in serum as test for congenital infection.

Maternal serum samples at 10 and 22 weeks of gestational age and cord blood samples were available from six cases of asymptomatic congenital human cytomegalovirus (HCMV) infection. Meaningful rises of serum IgG-antibody titers by ELISA occurred in three cases. Serum interferon (IFN)-gamma activity was detected in all six cases. Serum cell free soluble interleukin-2 receptor (sIL-2R) activity rose above the normal range (145-519 U/ml) in one IgG and IgM antibody-positive and three IgG antibody-positive woman. Serum levels of sIL-2R and IFN-gamma were not elevated in anti-HCMV antibody-negative healthy pregnant women. No HCMV IE DNA was detected by PCR in the serum of any of the pregnant women. HCMV DNA was detected in the serum of one of six infants with asymptomatic congenital HCMV infection. Assessment of the changes of serum cytokines such as sIL-2R and IFN-gamma in HCMV antibody-positive pregnant women may be useful for the prenatal diagnosis of active HCMV infection during pregnancy.

Cytomegalovirus↗
PubMed1998

Endogenous adenosine inhibits P-selectin-dependent formation of coronary thromboemboli during hypoperfusion in dogs.

The activation of platelets and the formation of neutrophil- platelet conjugates may lead to the development of thromboemboli. We studied whether blockade of adenosine receptors during coronary hypoperfusion may cause thromboemboli via P-selectin-dependent mechanisms in 30 open-chest dogs. When coronary blood flow was reduced to 20% of the control, it was stable at low levels with increases in adenosine levels. When 8-p-sulfophenyltheophylline, an adenosine receptor antagonist, was infused during coronary hypoperfusion, coronary blood flow decreased gradually and approached almost zero 20 min after its administration. Histological examination revealed thromboemboli in the small coronary vessels. During hypoperfusion in the presence of 8-p-sulfophenyltheophylline, the mAb against P-selectin attenuated both the reduction in coronary blood flow and the formation of thromboemboli, and improved contractile and metabolic dysfunction of the myocardium. Flow cytometric analysis indicated that the expression of P-selectin on platelet and neutrophil-platelet adhesion were increased during coronary hypoperfusion, and that both were further augmented by 8-p-sulfophenyltheophylline. Immunohistochemical examination showed no staining of P-selectin in the ischemic myocardium. Adenosine inhibited the thrombin-induced expression of P-selectin on platelet and neutrophil- platelet adhesion via adenosine A2 receptors. Adenosine appears to inhibit the formation of thromboemboli during coronary hypoperfusion by suppressing the expression of P-selectin on platelets and neutrophil-platelet adhesion.

Adenosine↗
PubMed1998

Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium.

Since angiotensin-converting enzyme (ACE) produces angiotensin II in the heart, ACE inhibitors may prevent coronary vasoconstriction and increase coronary blood flow. On the other hand, since ACE inhibitors also inhibit kininase II which results in reduced degradation of bradykinin, ACE inhibitors may increase cardiac nitric oxide (NO) levels via stimulation of bradykinin receptors. This study was undertaken to test whether ACE inhibitors increase the cardiac NO levels and coronary blood flow in the ischemic myocardium. In 34 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. When either imidaprilat or cilazaprilat of 3 microg/kg/min was infused into the bypass tube for 10 min after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 31 +/- 1 to either 45 +/- 5 or 43 +/- 4 ml/100 g/min despite no changes in coronary perfusion pressure (43 +/- 2 mmHg). During an infusion of either imidaprilat or cilazaprilat, bradykinin and the end-products of NO (nitrate + nitrite) concentrations of coronary venous blood were markedly increased, which were attenuated by either HOE-140 (an inhibitor of bradykinin receptors) or by N(omega)-nitro-L-arginine methyl ester (an inhibitor of NO synthase). We also observed increases in cardiac bradykinin and NO levels due to either imidaprilat or cilazaprilat in the low constant coronary blood flow condition. It is concluded that ACE inhibitors can increase cardiac NO levels via the accumulation of bradykinin in the ischemic myocardium.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Comparison of the ability of viral protein-expressing plasmid DNAs to protect against influenza.

The ability of plasmid DNA encoding various influenza viral proteins from the A/PR/8/34 (H1N1) virus to protect against influenza was compared in BALB/c mice. The plasmid DNA encoded hemagglutinin (HA), neuraminidase (NA), matrix protein (M1), nucleoprotein (NP) or nonstructural protein (NS1) in a chicken beta-actin-based expression vector (pCAGGS). Each DNA was inoculated twice 3 weeks apart at a dose of 1 microgram per mouse by particle-mediated DNA transfer to the epidermis (gene gun). Seven days after a second immunization, mice were challenged with the homologous virus and the ability of each DNA to protect mice from influenza was evaluated by decreased lung virus titers and increased survival. Mice, given HA- or NA-expressing DNA, induced a high level of specific antibody response and protected well against the challenge virus. On the other hand, mice given M1-, NP-, or NS1-DNA failed to provide protection, although M1- and NP-DNAs did induce detectable antibody responses. These results indicate that both HA- and NA-expressing DNAs for the surface glycoproteins are most protective against influenza from among the various viral protein-expressing DNAs used here.

Animals↗
PubMed1998

IgA antibody-forming cell responses in the nasal-associated lymphoid tissue of mice vaccinated by intranasal, intravenous and/or subcutaneous administration.

Effects of a single intranasal (i.n.), subcutaneous (s.c.) or intravenous (i.v.) vaccination and their combined vaccination of priming and boosting on a primary and a secondary IgA antibody forming cell (AFC) response were examined in the nasal associated lymphoid tissue (NALT), spleen and popliteal lymph nodes (pLNs) of BALB/c mice. Mice were primed with the vaccine prepared from A/Yamagata/120/86 (H1N1) together with a cholera toxin-adjuvant and boosted with the same vaccine 3 weeks later. Three days after boosting, IgA-AFC responses in each lymphoid tissue were measured as an index of the immunological memory that mediates a secondary IgA-AFC response. Single i.n. vaccination induced a greater primary IgA-AFC response in the NALT not only than that in the spleen or pLNs, but also than that induced by single i.v. or s.c. vaccination. The combination of i.n. priming and i.n. boosting afforded a greater anamnestic IgA-AFC response in the NALT not only than that in the spleen or pLNs, but also than that induced by any other combinations of priming and boosting (i.n.-i.v., i.n.-s.c., s.c.-i.n., s.c.-i.v., and s.c.-s.c.). These results showed that i.n. priming induced a greater primary IgA-AFC response in the NALT and simultaneously induced the immunological memory that mediated a greater secondary-type AFC response following i.n. boosting in the NALT.

Administration, Intranasal↗
PubMed1998

Antibody-forming cells in the nasal-associated lymphoid tissue during primary influenza virus infection.

Antibody-forming cell (AFC) responses in the nasal-associated lymphoid tissue (NALT) of BALB/c mice were examined following intranasal infection, mainly of the upper respiratory tract, with a small volume of influenza virus. The infection induced significant accumulation of T and B cells in NALT, peaking around day 7 post-infection. Virus-specific IgA, IgG and IgM AFC responses were induced, developing from day 5 and peaking at day 7; responses were predominantly IgA and IgG, followed by IgM. At peak, NALT contained the greatest number of IgA AFCs per total cells of the lymphoid tissues examined in the upper respiratory tract. The IgM AFC responses were induced in NALT cell cultures from uninfected mice following in vitro culture with influenza virus, indicating that at least a part of the AFCs in infected mice may have originated from specific B cell precursors in NALT. In parallel with the detection of AFCs in infected mice, virus-specific IgA antibodies appeared in the nasal wash and their appearance correlated well with virus clearance from the nasal area. These results suggest that virus-specific IgA antibodies, produced by IgA AFCs in NALT, play an important role in recovery from infection.

Animals↗
PubMed1998

Effects of ischemic preconditioning on contractile and metabolic function during hypoperfusion in dogs.

We examined the effects of ischemic preconditioning (i.p.) on metabolic and contractile function during coronary hypoperfusion in dogs. After the left anterior descending coronary artery (LAD) was occluded for 5 min (i.p.) and reperfused for 10 min, coronary blood flow (CBF) of the LAD was decreased to 33% of the control. I.p. increased (P < 0.05) lactate extraction ratio and the pH of coronary venous blood and decreased (P < 0.05) myocardial oxygen consumption and fractional shortening during hypoperfusion compared with those in the control group, although i.p. did not change the endocardial-to-epicardial blood flow ratio of the regional myocardium during hypoperfusion. I.p. increased (P < 0.05) the adenosine levels in coronary venous blood during hypoperfusion. I.p. increased (P < 0.05) myocardial ecto-5'-nucleotidase activity. Administration of 8-sulfophenyltheophylline or alpha, beta-methyleneadenosine 5'-diphosphate blunted the i.p.-induced changes in metabolic and contractile parameters during hypoperfusion. These results suggest that i.p. reduced the severity of anaerobic myocardial metabolism of ischemic hearts by increasing the adenosine levels via an extracellular pathway.

5'-Nucleotidase↗
PubMed1998

[Clinical study on cystinuria in children--the stone management and the prevention of calculi recurrence].

BACKGROUND: Cystinuria is an autosomal recessive disorder, and primary manifestation is the repeated formation of cystine calculi. Little information is available regarding clinical course of pediatric cystinuria having followed into adulthood. We report our experience with the management and the clinical course on cystinuria in children, who have been followed up for relatively long time. MATERIALS AND METHODS: We retrospectively reviewed the records of all pediatric patients with cystinuria in whom urolithiasis was treated from 1970 to 1996. RESULTS: A total of 15 pediatric patients with cystine calculi (9 boys, 6 girls) were treated in our hospital. Average age at diagnosis was 3 years 4 months old. Mean follow-up was 104 months. Stone location was upper urinary tract in 11 cases, bladder in 3 cases and both upper urinary tract and bladder in 1 case. Medical treatments including hydration, urine alkalization and dissolution therapy were performed in all patients. In three cases whose urinary cystine level ranged from 138 to 326 mg/gCr, cystine calculi were disappeared by medical therapy alone. In one of 3 cases vesicoureteral reflux was identified. Side effects were noticed in 30.0% of patients with tiopronin and in 85.7% of those with D-penicillamine, especially in 1 case with tiopronin nephrotic syndrome being noticed. Surgical procedures were performed in 13 patients (lithotomy: 17 calculi, endourology: 7 calculi and ESWL: 7 calculi). The stone free rate was 100% with lithotomy, 80 to 100% with endourology and 43% with ESWL at an average of 5.9 procedures. No complications were recognized after the surgical treatments. The stone events of 15 patients ranged from 0 to 1.5 (average 0.55). In all six patients followed up over the age of 20 years, stone recurrences were observed exclusively between 17 and 20 years of age. CONCLUSION: Dissolution therapy is more effective for cystinuric patients in whom urinary cystine excretion is less than 330 mg/gCr. For those cases with low urinary cystine level it is necessary to evaluate structural abnormalities of the urinary tract to avoid stone recurrence. ESWL and endourology should be tried for pediatric cystinuria except for neonates and infants, considering its safety. The patients and their parents must have adequate knowledge about the disease itself and its management. Prevention of cystine calculi recurrences depends on patient compliance to the therapeutic regimens necessitating close follow up according to the clinical conditions, especially for those in pubertic or postpubertic age.

Adolescent↗
PubMed1998

[A case of Prader-Willi syndrome accompanied with a renal stone].

Little information is available regarding the correlation between Prader-Willi syndrome and urolithiasis. We report a patient with Prader-Willi syndrome with a renal uric acid (UA) stone. A 23-year-old male patient was admitted to our department with gross hematuria and left flank pain. The blood and urine examination demonstrated hyperuricemia with the presence of UA crystals in the urine. Excretory urography revealed a radiolucent stone (17 x 27 mm) in the left renal pelvis suggesting a UA stone. The stone was removed successfully using extracorporeal shockwave lithotripsy (ESWL) combined with medication for UA metabolism. The stone was thought to have formed as a result of overeating associated with Prader-Willi syndrome, and accompanying overproduction of purine.

Adult↗
PubMed1998

[Intrapulmonary arterial injection of Albunex for left heart contrast echocardiography].

Contrast enhancement of the left heart cavity and myocardium were assessed after venous injection of the ultrasound contrast agent Albunex. Myocardial perfusion was also assessed using a drug stress and image analyzing system. The study population consisted of 46 patients with normal cardiac function and without coronary artery disease, and 38 patients with effort angina. Contrast echocardiography was performed by imaging the parasternal or apical long-axis view during pulmonary arterial injection of Albunex through a Swan-Ganz catheter. Contrast enhancement in the left ventricular cavity and ascending aorta were visually assessed. Hemodynamic, arterial blood gas and electrocardiography changes were recorded before and after the injection of Albunex. Contrast echocardiography was performed before and during intravenous infusion of dipyridamole to assess left ventricular myocardial enhancement by both visual inspection and peak background-subtracted gray level using an image analyzing system. Doppler flow signal change after the injection of Albunex was assessed in 26 patients using a Doppler guide wire located in the left anterior descending coronary artery. Good contrast enhancement was obtained in all patients in the left ventricular cavity and in 17% of patients in the ascending aorta. No significant changes were observed in hemodynamics, electrocardiograms and aortic gas analysis. Significant myocardial enhancement was not seen in any patient but gray level analysis of the echo images during dipyridamole infusion showed significant enhancement in 25% of the patients without coronary artery disease and in 34% of the patients with effort angina. Doppler flow signal in the coronary artery was significantly augmented in all patients after injection of Albunex and suggests that ultrasound contrast agent reaches coronary arteries in all patients regardless of myocardial contrast enhancement. Contrast echocardiography with pulmonary arterial injection of Albunex is safe and useful to obtain sufficient left ventricular contrast enhancement. For myocardial perfusion assessment, further refinement of the ultrasound contrast agent and echo equipment is necessary.

Adult↗
PubMed1997

Isolation and characterization of mouse nasal-associated lymphoid tissue.

A method for isolation of mouse nasal-associated lymphoid tissue (NALT), which is a principal mucosal lymphoid tissue of the respiratory tract in rodents, was developed. The paired lymphoid organs could be separated from the upper jaw by peeling away the palate where NALT was localized bilaterally on the posterior side. About 3 x 10(5) lymphocytes could be obtained from one NALT fragment. The NALT lymphocyte fraction from normal BALB/c mice contained T- and B-cells in about equal numbers, and contained about 4 times as many CD4+ T-cells as CD8+ T-cells when analyzed with a FACScan fluorescence analyzer. The composition of the NALT lymphocytes was similar to that of the lymphocytes from the portion of the nasal cavity remaining after isolation of the NALT. The NALT lymphocyte fraction from mice infected 7 days previously with influenza virus was also characterized. The numbers of NALT T- and B-cells from the infected mice were approximately 2 and 3 times higher than those of non-infected mice, respectively. In parallel with the cell increase, NALT lymphocytes produced IFN-gamma when cultured for 24 h and contained cells secreting influenza virus-specific IgA and IgG antibodies. The results suggest that this method can be successfully used for investigating cellular dynamics of mucosal immunology in the upper respiratory tract.

Animals↗
PubMed1997

Neurobiological basis of motor learning in mammals.

Long-term potentiation (LTP) has been proposed as a model of learning and memory. There is still little evidence, however, linking LTP to cognitive processes. We have chosen to study motor learning, first, because it is relatively simpler than cognitive learning and second, because much of the circuitry involved in motor function is already known. In behavioral studies we determined that the sensory cortex is required for the acquisition of new motor skills. Once a skill is acquired, however, the sensory cortex is no longer necessary in the performance of that skill. In electrophysiological experiments we have shown that LTP can be induced in the motor cortex with stimulation of the sensory cortex (SCx) or associativly when stimulation was applied to both SCx and thalamus. We propose that motor learning involves the formation of loop circuits between the motor cortex and the periphery involving the SCx and the thalamus. At first these loop circuits are diffuse, producing contraction of unnecessary muscles, but become specific by producing LTP through practice.

Animals↗
PubMed1997

A posterior lumbar approach for retroperitoneoscopic adrenalectomy: assessment of surgical efficacy.

OBJECTIVES: To compare the efficacy of retroperitoneoscopic adrenalectomy by a posterior lumbar approach (RPA) with that obtained by a transperitoneal anterior approach (TAA) or retroperitoneal lateral flank approach (RLA). METHODS: Fifty-one patients underwent endoscopic adrenalectomy by three approaches, including laparoscopic adrenalectomy by TAA in 33, retroperitoneoscopic adrenalectomy by RLA in 5, and retroperitoneoscopic adrenalectomy by RPA in 13. RESULTS: The average adrenal tumor size was 27 mm (range 8 to 65). The average number of trocars required for RPA was 3.2 which was significantly less than that for TAA and for RLA (4.2 and 4.1, respectively). The conversion rate to open surgery was 9.1% by TAA, 0% by RLA, and 7.7% by RPA. The average operating time for TAA was 252 minutes, which was significantly shortened to 194 minutes by RLA and 142 minutes by RPA (P < 0.02). The average blood loss was 101 mL for TAA and was negligible by RLA and RPA (22 and 32 mL. respectively). CONCLUSIONS: RPA allowed direct access to the main adrenal vascular supply before the gland was greatly manipulated. Endoscopic adrenalectomy by TAA or even by RLA required extra ports for retraction of liver, spleen, vena cava, or adrenal gland, with higher chance of vein avulsion. RPA was technically feasible and most effective for retroperitoneoscopic adrenalectomy in regard to the simplicity of vascular control. The operating time, perioperative morbidity, and cost were reduced with this approach.

Adrenal Gland Neoplasms↗