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Biomedical subjects

A Nakano

Publications and source records attributed to A Nakano.

At least 109 records · Page 6Linked to original sources

Comparison of two interferon alfa treatment regimens characterized by an early virological response in patients with chronic hepatitis C.

OBJECTIVE: We investigated the efficacy of an interferon regimen characterized by an early virological response in patients with chronic hepatitis C and evaluated whether the patient's virological status during therapy would be useful for predicting a complete response. METHODS: We treated 62 patients with chronic hepatitis C with 6 million units (MU) of human lymphoblastoid interferon daily for 4 wk. The serum HCV RNA was assayed at week 2 by the reverse transcription-polymerase chain reaction. HCV RNA-negative patients (group A) received 6 MU of interferon three times weekly for an additional 22 wk (total dose, 564 MU). HCV RNA-positive patients were randomly assigned to group B-1, which received the same regimen as group A, or to group B-2, which received 6 MU of interferon daily for 4 wk followed by 6 MU three times weekly for 18 wk (total dose, 660 MU). RESULTS: Complete responses were achieved by 19 (63.3%) of 30 group A patients, compared with one (6.3%) of 16 group B-1 patients and none of 16 group B-2 patients. The virological response at week 2 and the pretreatment serum HCV RNA level were independent significant predictors of a complete response. CONCLUSION: Patients who were still HCV RNA-positive at week 2 were unlikely to achieve a complete response after interferon therapy. An increase in the total dose of interferon failed to yield further benefit in these patients.

Adult↗

[Early manifestation of septic shock and disseminated intravascular coagulation complicated by acute myocardial infarction in a patient suspected of having Legionnaires' disease].

Legionellosis is an important cause of severe pneumonia in the community. Inadequate therapy will lead to respiratory distress syndrome, disseminated intravascular coagulation (DIC) and finally fatal multiple organ failure. We encountered a rare case in which early manifestation included septic shock and DIC complicated by acute myocardial infarction (AMI) suspected to be derived from Legionnaires' disease. A 54-year-old healthy female complained of lumbago, high fever and dry cough 10 days after visiting a hot spring spa. She was emmergently admitted due to shock. Physical examination demonstrated hypotension, high fever, course creakle in the right lower lung. Hepatosplenomegaly, lymphadenopathy and eruption were not found. WBC count was 34600/microliters with nuclear shift. CRP elevated. FDP, D dimer and TAT also elevated CPK elevated with dominance of the MB isozyme. Chest roentogenography revealed congestive heart failure, pleural effusion and obscure pneumonic shadow and EKG showed ST segment elevation in leads I, II, III, aVF, V4, V5, and V6. The patient was diagnosed as having septic shock, DIC and AMI. She was treated with gabexate mesilate, high dose methyl prednisolone and dopamine hydrochloride as well as piperacillin, meropenem, isepamycin and fluconzaole. Despite intensive care, the blood pressure fell again and pneumonia had progressed on the 8th hospital day. These antibiotics appeared to be ineffective. Erythromycin was then administered and a dramatic effect. was obtained as the patient recovered. Serum titer of Legionella pneumophila (serogroup 1) rose to 128-fold 2 weeks after the onset. Other serum titers such as Chlamydia psittaci, Rickettsia, Mycoplasma were all negative. Cultures obtained from the sputum, throat swab, urine and blood did not yield any microorganisms. Although the diagnosis could not be confirmed because the titer did not elevate over 256-fold of 4-fold within 2 weeks after the onset, Legionella infection was highly suspected from the clinical features. This is a rare case in which septic shock and DIC with AMI preceded pulmonary symptoms in a non-immunocompromised patient.

Diagnosis, Differential↗

Aortic regurgitation in a patient with primary antiphospholipid syndrome--a case report.

We present the case of a 39-year-old woman with aortic regurgitation that may have been induced by primary antiphospholipid syndrome. The patient had suffered recurrent miscarriages, thrombocytopenia, and deep-vein thrombosis for the previous 16 years, and had been diagnosed as having primary antiphospholipid syndrome 9 years previously because of a high titer of anticardiolipin antibody. She had been receiving medication for moderate hypertension for 7 years. The patient was admitted to Tenri Hospital because of heart failure, which was thought to be caused by moderate aortic regurgitation, moderate hypertension, and mild chronic renal failure. Echocardiography revealed thickened aortic and mitral valves. Primary antiphospholipid syndrome might have induced valve regurgitation as a result of valvular thickening.

Adult↗

Human chymase, an enzyme forming novel bioactive 31-amino acid length endothelins.

We report the novel role of human chymase in the production of bioactive 31-amino acid length endothelins (ETs), which may play a role in allergies and vascular diseases. In the bronchi of asthmatic patients, the vascular tissue in atherosclerosis, and the heart muscle in cardiac hypertrophy, both ET-like immunoreactivity and the accumulation of mast cells significantly increase. Chymase from human mast cells selectively cleaves big ET-1, -2 and -3 at their Tyr31-Gly32 bonds, and produces novel bioactive 31-amino acid length ETs, ETs(1-31), without any further degradation products. However, chymases from other species, human cathepsin G, and porcine alpha-chymotrypsin, degrade big ETs. ETs(1-31) at concentrations between 10(-9) M and 10(-7) M exhibited various contractile potencies in rat tracheae and porcine coronary arteries in a dose-dependent manner. Furthermore, ET-1(1-31) at concentrations between 10(-14) M and 10(-10) M caused a significant increase in the intracellular free Ca2+ concentration. The contractile activity of ETs(1-31) may not be the consequence of conversion to the corresponding ETs(1-21) by phosphoramidon-sensitive ET converting enzyme(s) or other chymotrypsin-type proteases and metallo-endopeptidases, because the contractile activity was not significantly inhibited on treatment with inhibitors of these proteases prior to the addition of ET-1(1-31).

Animals↗

Problems in pharmacological evaluation of patients with paroxysmal atrial fibrillation: clinical analysis of more than 100 consecutive patients.

To address the problems of pharmacological evaluation in paroxysmal atrial fibrillation (PAf), we interviewed 108 consecutive patients with documented PAf regarding symptoms, frequency and trigger factors of PAf and analyzed the 24-hour ambulatory electrocardiographic monitoring (Holter monitoring) records in relation to symptoms. Twenty-nine patients were totally asymptomatic, while 79 patients were symptomatic of which 49 patients had obvious trigger factors. PAf was documented by Holter monitoring in 22 of 79 symptomatic patients. On analysis of PAf-documented 25 Holter monitoring records, the patients checked event marks as PAf in only 20 of 155 PAf episodes. Six episodes of 26 event marks that patients thought to be PAf proved to be premature atrial or ventricular contractions. Nine patients in whom PAf persisted for more than 24 hours became asymptomatic. Patients suitable for pharmacological evaluation constituted about one-fifth of the PAf patients in our consecutive study. Even with the selection of these patients, pharmacological evaluation based on symptoms is difficult because disappearance of PAf may be associated with persistent atrial fibrillation.

Adolescent↗

[Echocardiographic and hematological variables as a risk factor for stroke in chronic nonvalvular atrial fibrillation].

The relationship between echocardiographic variables and the incidence of ischemic stroke in patients with atrial fibrillation was investigated by transthoracic and transesophageal echocardiography in 67 patients with chronic nonvalvular atrial fibrillation. Hematologic variables were also measured simultaneously, including plasma levels of D-dimer and thrombin-antithrombin III complex in these patients. There was a prior history of ischemic stroke in 13 patients (stroke group), but not in the other 54 patients (nonstroke group). There were no significant differences in age, sex, left ventricular ejection fraction, left ventricular end-diastolic diameter, left atrial diameter or hematologic parameters between the groups. The left atrial appendage emptying flow velocity was lower in the stroke group than in the nonstroke group (21 +/- 5 vs 32 +/- 3 cm/sec, p < 0.05), and the incidence of left atrial spontaneous echo contrast was significantly higher in the stroke group than in the nonstroke group (69% vs 26%, p < 0.01). There was no significant difference in the incidence of left atrial thrombi between the groups (23% vs 12%). These findings suggest that transesophageal echocardiographic variables are correlated with the risk of ischemic stroke in patients with chronic nonvalvular atrial fibrillation.

Adult↗

Prostaglandin E1 protects against ischemia-reperfusion injury of the liver by inhibition of neutrophil adherence to endothelial cells.

BACKGROUND: This study investigates the protective mechanism of prostaglandin E1 (PGE1) against hepatic ischemia-reperfusion injury in vivo. It has been demonstrated that activated leukocytes contribute to ischemia-reperfusion injury, and that administration of the monoclonal antibody (mAb) for adhesion molecules reduces the injury by inhibiting leukocyte-endothelial cell adhesion. We therefore attempted to find out whether PGE1 has an effect on the inhibition of neutrophil adherence to endothelial cells after reperfusion. METHODS: We administered anti-intercellular adhesion molecule 1 (ICAM-1) mAb, antiserum against rat polymorphonuclear leukocytes, or PGE1 to a rat model of left lobar ischemia for 60 min followed by reperfusion. Leukocyte adherence was observed by intravital fluorescence microscopy. The effect of PGE1 on the expression of adhesion molecules was analyzed by immunohistochemistry and flow cytometry. RESULTS: Ischemia-reperfusion caused endothelial dysfunction and hepatocellular injury with leukostasis in postsinusoidal venules. Anti-ICAM-1 mAb administration or leukopenia ameliorated both the hepatocellular injury and endothelial dysfunction. Although PGE1 administration did not affect the serum interleukin-8 level, it significantly decreased hepatic injury and leukostasis in the reperfused liver. Immunohistochemical findings showed that PGE1 decreased ICAM-1 expression on endothelial cells, but did not affect lymphocyte function-associated antigen 1, and membrane attack complex 1 on neutrophils in flow cytometric analysis. CONCLUSIONS: We conclude that PGE1 protects the liver against ischemia-reperfusion injury by reducing leukocyte-endothelial cell adhesion via down-modulation of ICAM-1 expression on the endothelium.

Alprostadil↗

Rer1p as common machinery for the endoplasmic reticulum localization of membrane proteins.

Rer1p, a Golgi membrane protein, is required for the correct localization of an endoplasmic reticulum (ER) membrane protein, Sec12p, by a retrieval mechanism from the cis-Golgi to the ER. To test whether or not the role of Rer1p is common to multiple ER membrane proteins, we examined the localization of two other ER membrane proteins, Sec71p and Sec63p, in the wild-type and rer1 mutant yeast cells, using their fusions with an alpha-mating factor precursor (Mfalpha1p). Although Sec71p and Sec63p have completely different topology from Sec12p, their Mfalpha1p fusion proteins were also mislocalized to the trans-Golgi in the rer1 mutant. Overexpression of these fusions caused their mislocalization to the trans-Golgi even in the wild-type cells, and this mislocalization was partially suppressed by the co-overexpression of Rer1p. Either Sec71p or an artificial chimeric protein whose ER localization depends on Rer1p gave a competitive effect on the localization of the Mfalpha1-Sec71p fusion, which was abolished in rer1. Thus, Rer1p appears to be one of the common limiting components in the retrieval machinery for ER membrane proteins. The results also suggest that Sec71p and Sec63p depend on ER-Golgi recycling, at least partly, for ER localization. We also examined the effect of a mutation in alpha-COP, a subunit of yeast coatomer, on the localization of these ER membrane proteins. The Mfalpha1p fusions of Sec12p, Sec71p, and Sec63p were all more or less mislocalized in ret1-1. These observations imply that the roles of Rer1p and coatomer are much more general than thought before.

Endoplasmic Reticulum↗

Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acid-length endothelins by chymase from human mast cells.

Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products. Chymases from other species, such as the enzymes from rat connective tissue and mucosal mast cells, and the other chymotrypsin-like proteases examined degraded big ETs. ETs(1-31) exhibited various contractile potencies as to the rat trachea in comparison with 21-amino acid-length endothelins, ETs(1-21), and big ETs: ET-1(1-21) > ET-1(1-31) > big ET-1; ET-2(1-31) > ET-2(1-21) > or = big ET-2; ET-3(1-21) > or = ET-3(1-31) > or = big ET-3. Among the ETs(1-31), ET-2(1-31) was the most potent constrictor, its potency being similar to that of ET-1(1-21) and stronger than that of ET-2(1-21). The contractile activity of ETs(1-31) may not be the consequence of conversion to the corresponding ETs(1-21) by phosphoramidon-sensitive ET-converting enzymes or other chymotrypsin-type proteases and metalloendopeptidases, because the contractile activity was not inhibited significantly on treatment with inhibitors of these proteases before the addition of ET-1(1-31). Inhibitors of chymotrypsin-type serine proteases, on the contrary, significantly enhanced the contractile activity exhibited by ET-1(1-31) and big ET-1, but not that by ET-1(1-21). These results suggest that protease(s) on the surface of the rat trachea tends to degrade ETs(1-31) and big ETs, and thereby reduces their contractile activity. Taken together, the results suggest that trachea-constricting ETs(1-31) generated by human chymase may play a role in the hyper-responsive airway in allergic inflammation.

Animals↗

Reproducibility of urinary beta 2-microglobulin and cadmium excretion among residents in a cadmium-polluted area during a 3-year period.

To assess the measurement error by using single exposure measurement in epidemiologic studies, reproducibility of urinary beta 2-microglobulin and cadmium excretion was evaluated among persons exposed to environmental cadmium. We measured urinary beta 2-microglobulin concentrations in 47 subjects four times and urinary cadmium concentrations in 48 subjects twice, during a 3-year period. Between-person and within-person variance components of these variables were estimated using a random-effects one-way analysis of variance model. The intraclass correlation coefficient (ICC) for urinary beta 2-microglobulin concentration, when expressed as microg/g creatinine and microg/l, was 0.92 and 0.89, respectively. The ICC for standardized urinary cadmium concentration (expressed as microg/g creatinine) was 0.81, while it decreased to 0.33 without standardization. The findings suggest that single measurement of urinary beta 2-microglobulin and cadmium, when expressed as a function of creatinine, can reliably estimate average levels over at least a 3-year period. Standardization of concentration using urinary creatinine improved reproducibility especially for urinary cadmium excretion.

Adolescent↗

Target cell-induced calcium signals in human natural killer leukemia cells as revealed by confocal fluorescence microscopy.

The target cell-induced calcium response in natural killer (NK) cells was examined using indo-1 (a ratiometric fluorochrome), a newly developed video-rate ultraviolet laser-scanning confocal microscope system, and a human NK leukemia cell line, YTN. Susceptible target cells (JY cells), but not unsusceptible target cells (K562 cells), increased the intracellular calcium concentration ([Ca]i) in almost all indo-1-loaded YTN cells with a lag time, although the kinetics of increase in [Ca]i differed in individual YTN cells. The increase in [Ca]i was completely blocked by 2 mM EGTA and partially (around 50%) blocked by 10 microM nicardipine, the extents of inhibition of calcium response correlating well with those of inhibition of cytotoxic activity. Thus, the calcium response in YTN cells observed in this study may constitute a critical step in the manifestation of cytotoxic activity.

Biological Transport↗

The role of lymph node dissection in the treatment of gallbladder carcinoma.

BACKGROUND: Lymph node involvement is an important prognostic factor in gallbladder carcinoma (GBC). The lymph node involvement pattern, extent, and indications for systematic lymph node dissection for patients with advanced GBC were investigated. METHODS: Forty-one patients with GBC who underwent radical resection with systematic regional lymph node dissection over the past 11 years were analyzed. RESULTS: The lymph node metastasis rate was 63.4% overall, 0% in pT1 disease, 61.9% in pT2 disease, and 81.3% in pT3/pT4 disease. When reviewed according to site, the rate was 41.5% in pericholedochal lymph nodes, 22.0% in the lymph nodes around the common hepatic artery and the portal vein, 36.6% in the posterior pancreaticoduodenal lymph nodes, 28% (5/18) in the celiac lymph nodes, 19% (3/ 16) in the superior mesenteric artery (SMA) lymph nodes, and 26% (7/27) in the aortocaval paraaortic lymph nodes. Patients with severe hepatoduodenal ligament invasion had high rates of paraaortic lymph node involvement. The mortality rate was 2.4% (1 of 41 patients) and the 5-year survival rate was 33.1% overall, 100% in patients with pT1 disease, 49.8% in patients with pT2 disease, and 0% in patients with pT3/pT4 disease. The 5-year survival rate for pT2 disease according to lymph node involvement was 72.7% in patients with pN0+ pN1+ positive posterior pancreaticoduodenal lymph nodes and positive lymph nodes around the common hepatic artery in the N2 patients and 0% in the patients with positive celiac and SMA lymph nodes in the N2 patient group or the positive paraaortic lymph node group (P < 0.05). CONCLUSIONS: These results suggest that systemic dissection of N1 lymph nodes, posterior pancreaticoduodenal lymph nodes, and lymph nodes around the common hepatic artery and the portal vein in N2 patients is necessary to improve the prognosis of those patients with pT2 disease without moderate or severe hepatoduodenal ligament invasion.

Adult↗

Delayed enhancement of myocardial FDG uptake on glucose loading FDG-PET in NIDDM patient.

We report a case of delayed enhancement of myocardial FDG uptake in NIDDM patient after oral glucose loading. A 65-year-old man who had a past history of NIDDM received FDG-PET examination during fasting and glucose loading. In neither condition, was an accumulation of FDG in the myocardium, and myocardial blood flow was normal. An oral glucose tolerance test (OGTT) was performed to find the best time for FDG injection and 3 hours after loading, the serum insulin concentration was increased significantly. When the interval between glucose loading and the injection of FDG was set at 3 hours, enhancement of myocardial FDG uptake was demonstrated. To know the best time for the FDG injection in advance is thought to be important in obtaining better image quality and interpreting the myocardial viability when FDG-PET examination during glucose loading is performed in NIDDM patients.

Aged↗

O-methylasparvenone, a nitrogen-free serotonin antagonist.

O-Methylasparvenone (1) and asparvenone (2) were isolated from an Aspergillus parvulus Smith broth in a microbial screening for 5-HT2C ligands and found to be 5-HT2C antagonists. They represent the first nitrogen-free serotonin ligands. The absolute configuration of 1 was determined to be S by X-ray analysis of the corresponding Mosher-ester. A short and efficient synthesis of rac-1 was developed. This protocol was applied to the synthesis of derivatives of 1 and a structure-affinity relationship was established.

3T3 Cells↗

Nailfold capillary abnormality and pulmonary hypertension in systemic sclerosis.

BACKGROUND: Patients with systemic sclerosis (SSC) show a capillary abnormality of nailfolds with controversial correlation with organ involvement. Our purpose was to study the correlation between this nailfold capillary abnormality and pulmonary hypertension in patients with SSC. METHODS: We studied the nailfold capillaries, using capillary microscopy, and the pulmonary arterial pressure, using right-heart catheterization, in 44 patients with SSC. Canonical discriminant analysis was used to define the capillary abnormality in patients with SSC, which was then compared with that of 40 normal controls. The correlations between the patterns of nailfold capillaries and the cardiopulmonary findings, including the pulmonary arterial pressure, were examined using Fisher's test. RESULTS: Thirty-two of 44 patients with SSC could be differentiated from normal controls by our definition of the SSC pattern. The SSC pattern correlated significantly with elevated pulmonary vascular resistance, as well as with pulmonary fibrosis, electrocardiographic abnormalities, decreased vital capacity, and decreased diffusing capacity for carbon monoxide. All SSC patients with pulmonary hypertension showed this SSC pattern. In patients with elevated pulmonary arterial pressure, capillary microscopy and diffusion capacity for carbon monoxide (DCCM) showed the highest rate of abnormalities. A limited-type SSC significantly correlated with DCCM and with anticentromere antibody, and the diffuse-type SSC with pulmonary fibrosis and anti-sci-70 antibody. CONCLUSION: Our data suggest that in patients with SSC, nailfold capillary abnormalities correlate with pulmonary arterial hypertension as well as with clinical and laboratory findings indicating pulmonary hypertension.

Adolescent↗