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We encountered 2 cases of intrapulmonary lymph node. Case 1 was in a 48-year-old woman who had been given a diagnosis of progressive systemic sclerosis. Case 2 was in a 49-year-old woman with idiopathic pulmonary fibrosis. In each patient, a follow-up chest CT scan showed a pulmonary nodule, which could not be seen on chest X-ray film. Each nodule has an irregular margin and a linear shadow resembling pleural indentation. Histological examination of the open biopsy specimens revealed that these nodules were intrapulmonary lymph nodes surrounded by interstitial pneumonia. Previous case reports and these 2 cases indicate that unless a thoracotomy is done intrapulmonary lymph nodes are difficult to distinguish from lung cancers.

A very small number of patients with asthma show symptomatic improvement after administration of aspirin and other cyclooxygenase inhibitors. The clinical features of such patients with so-called aspirin-relieved asthma are similar to those with aspirin-induced asthma, but the pathogenesis is unclear.We encountered one confirmed aspirin-relieved asthma patient and investigated the effects of cyclooxygenase and lipoxygenase inhibitors on his condition.Our patient showed a marked improvement of the forced expiratory volume in one second (FEV1) after administration of aspirin and three other cyclooxygenase inhibitors (indomethacin, mefenamic acid, and ketoprofen). A 5-lipoxygenase inhibitor (AA861, Takeda, Japan), however, evoked acute asthma, and repeated administration of this drug resulted in some desensitization, but not complete tolerance.These results suggest an altered balance of arachidonic acid metabolism may play a critical role in the pathophysiology of aspirin-relieved asthma.

The efficacy and safety of video thoracoscopic lung biopsy (VTLB) and of open lung biopsy (OLB) were compared in patients with diffuse lung diseases. Thirty-three patients who had undergone VTLB were retrospectively studied and compared with 67 patients who had undergone OLB. There were no significant differences in age (52.8 +/- 10.9 vs 53.4 +/- 10.3), in the number of biopsies per patient (2.6 +/- 0.6 vs 2.7 +/- 0.6), or in the rate of diagnosis (94% vs 93%) between the two groups. However, the rate of diagnosis was low when the number of VTLB or OLB performed per patient was low. The patients undergoing VTLB had significantly shorter operative times (VTLB, 100.2 +/- 27.2 min. vs OLB, 119.8 +/- 42.6 min; p0.01) and less blood loss (VTLB, 4.7 +/- 14.6 ml vs OLB, 65.7 +/- 77.0 ml; p0.001). Complications occurred in 3 of the 33 who underwent VTLB, and in 18 of the 67 who underwent OLB. These results indicate that VTLB is an effective and safe alternative in the diagnosis of diffuse lung diseases.

Urinary excretion of leukotrienes is greater in patients with aspirin-induced asthma (AIA) than in other patients with asthma in remission, and is greater still during an aspirin-induced attack. We therefore hypothesized that increased phospholipase A2 (PLA2) activity leads to increased leukotriene synthesis when non-steroidal antiinflammatory drugs inhibit cyclooxygenase in patients with AIA, and that PLA2 activity increases further during an aspirin induced attack. To test this hypothesis, we measured the serum PLA2 activity in adult asthmatic patients, and compared the activity in those with AIA to the activity in those without AIA. The subjects were 43 patients with asthma in remission, 17 with AIA and 26 without AIA. Serum PLA2 activity was also measured before and after intravenous administration of lysine-aspirin in three patients with AIA and in one without AIA. Serum PLA2 activity was measured by radioimmunoassay. Serum PLA2 activity in patients with AIA, in those without AIA, and in healthy controls was 300.9 +/- 52.9, 294.4 +/- 65.3 and 171.7 +/- 41.8 pmol/ml/min, respectively. Serum PLA2 activity in asthmatic patients was significantly higher than in healthy controls (p0.01), but there was no difference between patients with and without AIA. Intravenous lysine-aspirin provoked asthmatic attacks in three patients with AIA. However, intravenous lysine-aspirin did not significantly change serum PLA2 activity in the three patients with AIA or in the patient without AIA. These results indicate that although PLA2 may be involved in the pathogenesis of bronchial asthma, it is not specific to AIA. Thus, the pathophysiology of AIA remains unclear and further investigation is needed.

The mechanism of osteoclast-like cell formation induced by periodontopathic bacterium Actinobacillus actinomycetemcomitans Y4 (serotype b) capsular-polysaccharide-like polysaccharide (capsular-like polysaccharide) was examined in a mouse bone marrow culture system. When mouse bone marrow cells were cultured with A. actinomycetemcomitans Y4 capsular-like polysaccharide for 9 days, many multinucleated cells were formed. The multinucleated cells showed several characteristics of osteoclasts, including tartrate-resistant acid phosphatase (TRACP) and the ability to resorb the calcified dentine. In this study, we examined the effects of antisera to interleukins on the formation of osteoclast-like cells induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. Monospecific anti-mouse recombinant interleukin-1 alpha (rIL-1 alpha) serum completely inhibited the formation of osteoclast-like cells in the presence of A. actinomycetemcomitans Y4 capsular-like polysaccharide. However, anti-mouse rIL-1 beta and anti-mouse rIL-6 sera showed no effect on osteoclast-like cell formation. IL-1 receptor antagonist significantly inhibited the osteoclast-like cell formation mediated by A. actinomycetemcomitans Y4 capsular-like polysaccharide in mouse marrow cultures. The bioactive IL-1 was detected in the culture media of mouse bone marrow cells stimulated with A. actinomycetemcomitans Y4 capsular-like polysaccharide. These results indicate that IL-1 alpha is involved in the mechanism of the formation of osteoclast-like cells induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. We sought to determine whether osteoclast-like cell formation induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide could be modulated by the protein kinase inhibitors H8 and HA1004. The formation of osteoclast-like cells was suppressed by H8 and HA1004. These findings suggest that the signals by protein kinases may regulate osteoclast-like cell formation induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. Furthermore, a correlation between IL-1 alpha and prostaglandin E2 in the osteoclast recruitment induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide is discussed.

Absorption, distribution, excretion and metabolism were studied in rats and mice after oral and intravenous administration of 5 mg/kg of [14C] T-3761. 1. [14C] T-3761 was rapidly absorbed after oral administration and maximum serum concentration of radioactivity was observed at 15 min. and at 10 min. in rats and mice, respectively. After that, radioactivity of serum declined rapidly. 2. The administered radioactivity was excreted mainly in the urine in rats and mice and excretion rate was 84% and 74%, respectively. The residual radioactivity was excreted in the feces. In both species, the urinary excretion rate after oral administration was similar to that after intravenous administration, suggesting that [14C] T-3761 was absorbed almost completely. 3. In the rat urine, over 90% of excreted radioactivity was T-3761. On the other hand, about 57% of excreted radioactivity was presumed to be glucuronide conjugate of T-3761 in the mice urine. 4. The biliary excretion of radioactivity in rats after oral administration was approximately 22%, and about 83% of those was presumed to be glucuronide conjugate. About 40% of the excreted radioactivity was reabsorbed from the intestinal tract. 5. Except gastrointestinal tract, tissue concentration of radioactivity after oral administration was high in kidney and liver. Radioactivity was widely distributed in other tissues at lower concentration than in the plasma, whereas hardly distributed in brain and spinal cord. 6. Whole body autoradiograms in rats indicate that radioactivity were widely distributed except central nervous systems. 7. The extent of the binding of [14C] T-3761 to serum protein was 23-31% and 25-34% in rats and mice, respectively.

The affinity of T-3761 to melanin was examined with synthetic melanin comparing other quinolones. The binding rates with synthetic melanin were from 37% to 48% for tosufloxacin, sparfloxacin, ciprofloxacin and norfloxacin. Binding rate of ofloxacin at 28% was lower and T-3761 was lowest at 22%. Intraocular dynamics of T-3761 and ofloxacin were investigated in pigmented rabbits after a single oral administration at a dose of 20 mg/kg. In both drugs, the concentrations in the melanin bearing tissues were higher and the disappearances from the melanin bearing tissues were more slowly than those of the non-melanin bearing tissues. T-3761 concentrations in the melanin bearing tissues were significantly lower than ofloxacin. In vitro uptake amount to melanin bearing tissue of ofloxacin was 1.4-2.4 times larger than that of T-3761.

Placental transfer and mammary excretion of radioactivity were investigated in the pregnant rats on day 19 of pregnancy, in the pregnant mice on day 18 of pregnancy, and in the lactating rats after oral administration of 5 mg/kg of [14C] T-3761. 1. Transfer of radioactivity to fetus was observed in rats and mice and the concentration in fetus was 0.2-0.5 times higher than the maternal plasma. 2. The radioactivity was excreted into the milk and the concentration in milk was higher than those of blood levels (milk/blood = 1.3-5.8). The radioactivity in milk declined more slowly than in blood.

M2-cholinergic receptor activation by acetylcholine (ACh) is known to cause a negative inotropic and chronotropic action in atrial tissues. This effect is still controversial in ventricular tissues. The ACh-sensitive muscarinic K+ channel (IK(ACh)) activity was characterized in isolated feline atrial and ventricular myocytes using the patch-clamp technique. Bath application of ACh (1 microM) caused shortening of action potential duration without prior stimulation with catecholamines in atrial and ventricular myocytes. Resting membrane potential was slightly hyperpolarized in both tissues. These effects of ACh were greater in atrium than in ventricle. ACh increased whole-cell membrane current in atrial and ventricular myocytes. The current-voltage (I-V) relationship of the ACh-induced current in ventricle exhibited inward-rectification whose slope conductance was smaller than that in atrium. In single channel recording from cell-attached patches, IK(ACh) activity was observed when ACh was induced in the pipette solution in both tissues. The channel exhibited a slope conductance of 47 +/- 1 pS (mean +/- SD, n = 14) in atrium and 47 +/- 2 pS (n = 10) in ventricle (not different statistically; NS). The open times were distributed according to a single exponential function with mean open lifetime of 2.0 +/- 0.3 msec (n = 14) in atrium and 1.9 +/- 0.3 msec (n = 10) in ventricle (NS); these conductance and kinetic properties were similar between the two tissues. However, the relationship between the concentration of ACh and single channel activity showed a higher sensitivity to ACh in atrium (IC50 = 0.03 microM) than in ventricle (IC50 = 0.15 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Four cases of thrombocytosis in three successive generations of a family are described. High peripheral platelet count was found incidentally in the proband with cutaneous malignant lymphoma. Bone marrow examination showed megakaryocytic hyperplasia. Neither Philadelphia chromosome nor chimaeric bcr/abl junction was detected in marrow cells. In this family, thrombocytosis was thought to be transmitted by an autosomal dominant mode of inheritance.

T lymphocytes in bronchoalveolar lavage (BAL) fluid from patients with sarcoidosis are activated. They are thought to recognize as yet unknown antigens and to play an important role in the pathogenesis of the disease. We studied the use of the T cell receptor V beta gene of lymphocytes obtained by BAL and lymphocytes obtained from peripheral blood of 11 patients with sarcoidosis and 9 normal controls, using the reverse transcriptase-polymerase chain reaction. As compared to the normal controls, V beta 2 and V beta 6 genes were predominantly expressed (15% of the sum of all V beta transcripts) on lymphocytes obtained from BAL fluid in 4 and 7 of 11 patients with sarcoidosis, respectively, but no specific V beta gene was predominantly expressed on lymphocytes obtained from peripheral blood. These results imply that those lymphocytes that are obtained from BAL fluid and that express V beta 2 and V beta 6 genes are involved in the pathogenesis of sarcoidosis.

We investigated factors affecting net transperitoneal calcium balance (Ca-BL) and the level of parathyroid hormone in relation to stepwise changes in serum calcium, by short PET (peritoneal equibrium test during 240 min: using 2000 ml of 2.5% dextrose dialysate containing 1.75 mmol/L Ca) in uremic patients undergoing stable CAPD. We calculated Ca-BL (mg/effluent/PET) of 244 effluents obtained from 90 patients receiving calcium carbonate as a phosphate binder without vitamin D supplementation. Their serum calcium level corrected with albumin (cSCa), alkaline phosphatase activity (ALP) and intact-PTH level was 9.7 +/- 0.9 mg/dl, 236 +/- 83 mIU/ml and 153.0 +/- 172.4 pg/ml, respectively. We proposed two statistic significant regression lines between Ca-BL and total drainage effluent volume (Ca-BL = 133X - 0.056: r = 0.981, P0.001), cSCa (Ca-BL = -12.9X + 123.6: r = 0.941, P0.01). Total drainage volume (TDV) and cSCa were two major factors affecting Ca-BL. A TDV level of 2430 ml/240 min-PET or more was required for positive Ca-BL in cases with 9.5-10.0 mg/dl of cSCa, using this linear regression analysis. A cSCa level of 9.6 mg/dl or more was also required for positive Ca-BL in cases with 2400-2600 ml/240min-PET. We also proposed a significant linear regression line between the intact-PTH level and cSCa (i-PTH = -90.5X + 1015.8, r = 0.973, P0.01). This line suggest that 200 pg/ml of intact PTH was obtained by 9.0 mg/dl or less of cSCa level in 90 CAPD uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Event-related (ER) signal-averaging technique was used to evaluate whether beat-to-beat changes of filtered QRS complex possibly relate to the appearance of ventricular arrhythmias (VA) or not. 82 patients with premature ventricular contractions (PVC) were studied. ANALYSIS-I:56 pts (16 with VT): a conventional method, in which all sinus beats were averaged (ALL), was compared with the new ER methods, in which only sinus beats immediately before (B) or after (A) each PVC can be separately averaged. ANALYSIS-II: 26 pts (10 with VT): five modes of ER averaging, 2nd preceding (2-B), just preceding (1-B), immediately after (1-A), 2 beat after (2-A), and isolated (ISO) from each PVC, were compared.I: Significantly longer F-QRS and smaller RMS40 than ALL were observed at B both in VT+ and VT- pts. These transient changes tended to remain even at A only in VT+ not in VT+ pts.II: No significant changes compared with ISO were seen at 2-B and 2-A at all. The widening of F-QRS and the decrease of RMS40 occurred only at 1-B in VT- and unti 1-A in VT+ pts. In conclusion, pre- and post- extra-systolic changes of filtered QRS complex were very transient and event-related, suggesting the close relationship to the mechanism of VA.

Reaction of the lithiated species of 9-(2,3,5-tris-O-tert-butyldimethylsilyl-beta-D-ribofuranosyl)-6-chloropu rine with Me3SiCl or Bu3SnCl was found to furnish the corresponding C-2 substituted product, as a result of silyl or stannyl migration from C-8 to C-2 position.

T lymphocytes in bronchoalveolar lavage (BAL) from idiopathic interstitial pneumonia (IIP) patients are considered to recognize unknown antigens, such as dust, fume, virus or degenerated autoantigens. To analyse the nature of these T lymphocytes, we investigated T cell receptor (TCR) V beta gene usage (22 kinds) in BAL Lymphocytes and Peripheral blood lymphocytes from 10 11P patients and 9 normal controls, using reverse transcriptase-polymerase chain reaction method. In BAL lymphocytes, predominant usage of V beta genes (15% of the sum of all V beta transcripts) was recognized in 7 of 10 IIP patients, which appeared to vary in individuals (Case 1: V beta 14, case 2: V beta 3, V beta 5.1, case 5: V beta 2, case 6: V beta 6, case 7: V beta 8, case 8: V beta 7, V beta 20, case 9: V beta 6), whereas no predominant V beta usage was demonstrated in normal controls. It remains to be elucidated whether the BAL lymphocytes expressing predominant V beta genes are involved in the activation of alveolar macrophages, fibroblasts, thereby inducing the production of autoantibodies.

The high-spin level structure of 186Au is re-investigated by means of in-beam γ-ray spectroscopy via the 172Yb(19F, 5nγ)186Au reaction. The oblate bands previously reported are revised and extended to higher-spin states. A new Iπ = (20+) excited state has been identified and assigned to the πh−111/2 ⊗ νi−213/2h−19/2 configuration. The total Routhian surface and cranked shell model calculations suggest that the πh−111/2 ⊗ νi−213/2h−19/2 band in 186Au has a non-axial deformation.

Plasmodium falciparum human malaria parasites establish unique membrane systems in the cytoplasm of their host erythrocytes. These systems include Maurer's Clefts (MCs), which are evident as small membranous structures in host erythrocyte periphery and are thought to support the trafficking of P. falciparum proteins to the host cell surface. Three-dimensional structures of MCs and their tethering to the host erythrocyte membrane have been reported from reconstructions of transmission electron microscopy (TEM) and fluorescence images (Hanssen et al. Mol. Microbiol. 2008 Feb;67(4):703–18.). To examine the structure of MCs and their proximal interactions in host erythrocytes, we have used an unroofing/rip-off method to expose the intracellular contents of parasitized erythrocytes and collect structural information by TEM. MCs in the unroofed TEM images range in dimension from 200 nm to 700 nm and have easily-resolved tethers that are 170 nm to 450 nm in length. These tethers are present in networks that connect the MCs to the skeleton of the host erythrocyte membrane.

Coronary artery calcification (CAC) was easily demonstrated by plain CT-scan. The aim of this study was to clarify the clinical significance of CAC in cardiovascular diseases. The subjects were 90 patients with ischemic heart disease (30 myocardial infarction, 50 exertional angina pectoris and 10 variant form of angina pectoris; 46 males and 44 females, 68 +/- 10 y/o) and 50 patients without ischemic heart diseases (30 hypertension, 10 arrhythmia, 3 valvular disease, 2 cardiomyopathy, 2 congenital heart disease and 3 others; 25 males and 25 females 65 +/- 9 y/o). CAC and calcification of thoracic aorta were evaluated by plain CT-scan (1 second scan time and 5 mm slice). The relationship between CAC and other clinical features (age, sex, hypertension, diabetes mellitus, hyperlipidemia, smoking, resting ECG, exercise stress ECG, aortic calcification and optic fundi) were studied. CAC were seen more frequently in patients with ischemic heart disease (63%), old age (67%), aortic calcification (70%) and positive exercise testing (64%). On the other hand, CAC were rare in variant angina (30%). In younger patients (under 70 y/o), CAC were seen more frequently in diabetic patients. But, in older patients, CAC were frequently in those with hyperlipidemia. These results suggested that CAC was associated with not only systemic arteriosclerosis, but also ischemic heart disease, except vasospastic angina. The prognostic value of CAC would be studied later.

A 54-year-old woman was admitted to our hospital because of an asthmatic attack. Her first asthma attack occurred when she was 53 years old. It was followed by a flu-like infection, and was preceded for one year perennial rhinitis and loss of the sense of smell. Symptoms were perennial, and unrelated to the seasons. Because these clinical findings resembled those of aspirin-induced asthma (AIA), an aspirin-DL-lysine i.v. challenge test was done. Cough, perspiration, and flushing was provoked within 15 min after aspirin-DL-lysine injection, but FEV1 did not change. Respiratory sounds were normal and no wheezing was audible. Other cyclooxygenase inhibitors (ketoprofen, sulpyrine and acetaminophen) provoked the same symptoms. Successively increasing doses of injected aspirin-DL-lysine resulted in complete tolerance to this stimulus. We propose that aspirin-induced cough without bronchoconstriction is a new type of aspirin hypersensitivity.

A 76-year-old man was admitted to our hospital in December of 1990, for investigation of progressive dyspnea on exertion over the previous 3 months. Physical examination revealed cyanosis, but no edema. Cardiomegaly was seen on chest X-ray, and findings compatible with right-sided congestive heart failure were revealed by ECG and echocardiography. Lung perfusion scintigrams showed multiple defects in both lungs, but no abnormal findings were detected on a ventilation study. Venograms of the lower extremities disclosed thrombosis of the right femoral vein. Therefore, a diagnosis of recurrent pulmonary thromboembolism was made. Furthermore, lupus anticoagulant and IgG-class anticardiolipin antibody were noted in the serum. The patient was treated with intravenous heparin, long-term warfarin, and transvenous placement of a Greenfield filter in the inferior vena cava. The clinical symptoms and signs improved, and no recurrence has been seen during the 13 months since the onset. On discharge, both antiphospholipid antibodies were negative. This case of primary antiphospholipid syndrome without autoimmune disease, with transiently positive antibodies only in the exacerbation phase, is discussed herein.

Two subtypes (alpha 1A and alpha 1B) of alpha 1-adrenoceptors have been defined on the basis of radioligand binding studies with 2-(2,6-dimethoxyphenoxyethyl)-1,4-benzodioxane (WB4101). In contrast, functional studies with blood vessels have proposed another subclassification, where the alpha 1-adrenoceptors can be classified into putative two (alpha 1H and alpha 1L) or three (alpha 1H, alpha 1L and alpha 1N) subtypes. The present study was performed to elucidate the effects of repeated treatment with electroconvulsive shock (ECS) or imipramine on the subtypes of alpha 1-adrenoceptors. The density of the alpha 1H binding sites (including alpha 1A and alpha 1B binding sites) in the frontal cortex was increased by repeated treatment with ECS but decreased by imipramine. These treatments did not change the density of alpha 1L binding sites. These results indicated that repeated treatment with ECS and imipramine had different effects on the alpha 1H binding sites in the rat frontal cortex. In addition, the effects of antipsychotic drugs, antidepressant drugs and calcium channel antagonists on [3H]prazosin binding were studied. The order of inhibition of [3H]prazosin binding was: antipsychotic drugs (1.4-4.2 nM)antidepressant drugs (69-116 nM)calcium channel antagonists. The calcium channel antagonists, verapamil (720 nM), diltiazem (4.3 microM) and nicardipine (75 microM) were weakly bound. These results suggested that the antimanic effects of calcium channel antagonists were not associated with inhibition of alpha 1-adrenoceptors.

A 44-year-old female was admitted to our hospital for the purpose of undergoing hysterectomy for removal of multiple uterine tumors. A chest X-ray film obtained on admission revealed a solitary nodule in the right lung field. The resected specimen containing the uterine tumors revealed well differentiated leiomyoma with no nuclear atypia or mitotic figures. The resected specimen from the pulmonary tumor revealed histologic findings similar to those of the uterine myomas, being devoid of any signs of mitosis. Similar cases have been reported as so-called benign metastasizing leiomyoma, and are generally regarded as low grade malignancy or leiomyomatosis. However, we consider this case to have had a primary pulmonary leiomyoma associated with uterine myoma since the pulmonary lesion was solitary and no mitotic figures were detectable. As the concept of metastasizing leiomyoma is confusing, the accumulation of additional case reports is necessary.

A 41-year-old male developed acute interstitial pneumonia after inhalation of Blasticidin S, an antibiotic effective against rice blast disease. He presented with diarrhea, followed by dry cough, dyspnea and fever. A chest roentgenogram showed bilateral diffuse ground glass appearance, superimposed by patchy shadows. Arterial blood gas analysis revealed severe hypoxemia. Bronchoalveolar lavage fluid specimen showed moderate increase in total cell count, lymphocytes, neutrophils and eosinophils with marked elevation of CD4/8 ratio. Antibiotic therapy with minocycline failed to improve his condition, and methylprednisolone pulse therapy followed by methylprednisolone (48 mg) resulted in clinical remission with resolution of the chest roentgenogram findings. Blasticidin S should be kept in mind as a causative agent of acute interstitial pneumonia.

The clinical course and prognosis of 20 consecutive patients aged over 16 years with atrial septal defect and pulmonary hypertension were analyzed. All patients, six men and 14 women, underwent cardiac catheterization at an average age of 43 years and received medical treatment. All patients with the ostium secundum type had a systolic pulmonary arterial pressure of 87 +/- 18 mmHg (mean +/- SD) and a pulmonary arteriolar resistance of 17 +/- 11 U.m2. At a mean follow-up period of 8 years, nine patients had died of cardiac causes at a mean age of 51 years, 10 were alive, and one was lost to follow-up. Five out of 13 patients with a pulmonary arteriolar resistance of 14 U.m2 or more had died of progression of the pulmonary vascular obstructive disease. Two of the seven patients with a pulmonary arteriolar resistance less than 13 U.m2 had died of pulmonary vascular obstructive disease and another two died of congestive heart failure. Although 25% of the patients had become symptomatic before 20 years of age, the diagnosis of atrial septal defect was not made until a mean age of 39 years. Eighteen patients became more severely symptomatic, but the time until the development of the symptoms varied. The mean age of patients in the New York Heart Association class I, II, III-IV were 27, 38, and 48 years of age, respectively. The percent survivals at 50 and 60 years of age were 77% and 54%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been widely recognized that the elderly shows an increased prevalence of cardiac arrhythmias. Moreover, the elderly population presents a number of problems to the clinician prescribing antiarrhythmics, such as drug accumulation, low compliance and proarrhythmias. In this article, we discussed age-related changes of the pharmacokinetics and the pharmacodynamics of antiarrhythmics with reference to proarrhythmia in the elderly. Age-dependent decrease of renal creatinine clearance plays an important role in the pharmacokinetics in the elderly. Age-related changes of pharmacodynamics of antiarrhythmics have not been evaluated extensively. Our results concerning the effect of class 1a drug on filtered QRS width on signal-averaged ECG, demonstrated age-related accentuation of class 1 action. In terms of non-pharmacologic treatment, physiological pacing is useful especially on elderly patients. The indications for catheter ablation and implantable cardiverter-defibrillators for the elderly should be established in detail.

A 23-year-old woman was admitted to our hospital because of cough and fever. Coarse crackles were audible over her left chest. A chest X-ray obtained on May 5, 1989, showed consolidation in the left S10 and a nodule in the right S1. Clinical symptoms improved during the course of hospitalization. Neither antibody titers against mycoplasma and chlamydia nor viral titers were elevated in paired sera. BALF findings of the left B10 showed increased numbers of eosinophils and lymphocytes. We diagnosed this case as eosinophilic pneumonia (EP). Environmental provocation testing was carried out in her home and yielded a positive result. After clearing of the house, she was able to return and has since experienced no relapses. We suspect that environmental conditions influence the pathogenesis of EP.

The effects of chronic administration of clomipramine or citalopram (CMI or CIT, 20 mg/kg i.p. daily for 19 days) with/without short-term administration of lithium (Li, 2 mEq/kg i.p. daily for 5 days) on the concentration of monoamines and their metabolites and serotonergic receptors were studied in the rat cerebral cortex. Li or CMI by itself had no effects on the concentration of monoamines and their metabolites, but a combination of CMI and Li increased that of 5-HIAA. CIT alone increased that of 5-HIAA, and a combination of CIT and Li increased that of 5-HIAA more than CIT alone. There were no changes in 5-HT or 5-HIAA after acute administration of CMI or CIT with/without Li. For the serotonergic receptors, [3H] 8-OH-DPAT and [3H] paroxetine binding did not change in any of the treatments. CMI alone or a combination of CMI and Li reduced [3H] ketanserin binding, but Li did not potentiate this effect. It is speculated that the therapeutic action of Li when added to tricyclic antidepressants in the treatment of refractory depression may partly have its basis in potentiation of effects on the activation of presynaptic serotonergic system.

Erbium-doped fiber amplifier (EDFA) is an indispensable element for AM-FDM optical video distribution systems to allow long transmission distances and branching losses. However, there is a problem of gain tilt of EDFA combined with laser chirp, which leads to the composite second-order (CSO) distortion[1]. It is also reported that the gain tilt for RF modulated light (AC gain tilt) is severa1 times as large as conventional DC gain tilt, and its spectral behavior is similar to the small signal gain spectrum[2]. Therefore, the small signal gain peak of EDFA must be at the signal wavelength to minimize the CSO distortion

The objective of this study was to investigate the effects of a dihydropyridine calcium antagonist, manidipine HCl, and an angiotensin II receptor antagonist, CV-11974, on renal microvasculature in hypertensive rats. Hydronephrosis was induced by ligation of the left ureter in 8-week-old stroke-prone spontaneously hypertensive rats. Two months after the operation, the hydronephrotic kidney was split longitudinally and spread out as a thin sheet, and the renal microvasculature was observed directly under a light microscope. Administration of manidipine HCl (20 micrograms/kg) caused a gradual fall in blood pressure (-34 mmHg). The afferent arterioles were dilated, and maintained the same level of dilatation until 30 min (+20%). The efferent arterioles were also dilated (+8%). Glomerular blood flow was significantly increased (+38%). Administration of CV-11974 (100 micrograms/kg) caused a sharp fall in blood pressure at 2 min (-24 mmHg), with a continuous fall in blood pressure until 60 min (-46 mmHg). The afferent arterioles were gradually dilated (+15%). The efferent arteriole was also dilated until 60 min, but to a lesser extent than the afferent arteriole. Glomerular blood flow was immediately increased (+35%). We conclude that both manidipine HCl and CV-11974 dilated both the afferent and efferent arterioles and increased glomerular blood flow.

Summary form only given. Since the introduction of magnetic wood, the authors have proposed various functions such as heating, attraction and electromagnetic wave absorption. The impregnated type magnetic wood, which is manufactured by impregnating magnetic fluid through conduit pipes, has the best woody characteristics among the three types of magnetic woods (impregnated type, powder type and coating type). In spite of the merits, the manufacturing methods up until now have been unsuccessful in producing an impregnated type magnetic wood with good magnetic characteristics, because it is difficult to impregnate a sufficient amount of magnetic fluid into the wood board. The purpose of this paper is to suggest a new impregnating method and report on the experimental results of DC and AC magnetic characteristics. The manufacturing method involves taking a thin layer of film from the wood and impregnating this section with a magnetic fluid. Next, these layers are laminated and adhered to create a board. Comparative measurements were made of the specific gravity of the laminated impregnated type and impregnated type magnetic woods. The experimental results for the proposed laminated impregnated type show that uniform magnetic characteristics are obtained and apparently good characteristics are shown from DC to 13.5 GHz.

Cell sorting is an important part of the sperm sexing process. The objective of this study was to compare the efficiency of in vitro embryo production using sexed frozen–thawed bull sperm sorted with 2 types of cell sorter. Ejaculates from 2 Bos taurus (Holstein, 5 years old) bulls underwent conventional processing (control) or sorting for X chromosome bearing sperm using MoFlo® SX (SX, Dako, Fort Collins, CO, USA) or MoFlo® XDP-SX (XDP, Beckman Coulter, Fullerton, CA, USA) following XY™ sperm-sorting protocols. Processed sperm samples were cryopreserved in 0.5-mL plastic straws. Cumulus–oocyte complexes obtained from abattoir-derived ovaries were matured for 20 h in HEPES–TCM-199 (Lu and Seidel 2004 Theriogenology 62, 819–830) and randomly assigned to each of 3 sperm treatment groups. Thawed sperm were centrifuged for 20 min at 448 × g through an ISolate® (Irvine Scientific, Santa Ana, CA, USA) gradient (45:90%). Sperm pellets were washed in IVF100 (Hoshi 2003 Theriogenology 59, 675–685) by centrifugation for 5 min at 252 × g. Oocytes were co-incubated with washed sperm (5 to 10 × 106 sperm mL–1) in IVF100 (Hoshi 2003 Theriogenology 59, 675–685) for 8 h at 38.5°C in 5% CO2 and 95% air (Day 0). Presumptive zygotes were cultured for 90 h in CDM-1 (Lu and Seidel 2004 Theriogenology 62, 819–830) and then washed and cultured in IVD101 (Hoshi 2003 Theriogenology 59, 675–685) at 38.5°C in 5% CO2, 5% O2, and 90% N2. Cleavage rates on Day 2 and blastocyst rates on Day 7 to 9 were recorded after insemination. Two-way ANOVA was used for data analysis, followed by Fisher’s PLSD test. Experiments were replicated 4 times for bull A (total of 1 350 oocytes used) and 5 times for bull B (total of 1 529 oocytes used). The data are summarised in Table 1. No interaction was observed between the treatments and bulls. Cleavage rates were not significantly different in the 3 treatment groups. However, blastocyst rates were significantly lower in both SX (P 0.8). Bull B showed significantly poorer results than bull A regarding both cleavage (P

We report two cases of idiopathic interstitial pneumonia (IIP) with acute deterioration after bronchoalveolar lavage (BAL). Case 1 was a 54-year-old woman, and case 2 was a 75-year-old man. Both were diagnosed as having IIP, and hospitalized with complaints of high fever and dyspnea. After BAL, the degree of dyspnea increased. White blood cell count and lactate dehydrogenase were elevated, and PaO2 was decreased. Chest X-ray revealed consolidation of the upper lung fields and reticulo-granular shadows spreading through both lungs. BAL fluid examination showed an elevated neutrophil fraction (case 1: 6.5%, case 2: 35.2%), suggesting respiratory tract infection although bacteria could not be detected. Case 1 died of respiratory failure despite corticosteroid therapy. Autopsy revealed diffuse alveolar damage with focal pneumonia in the right S6 corresponding to the upper lobe consolidation. Case 2 improved after antibiotic therapy. These findings suggest that aspiration of infected fluid during BAL can cause acute exacerbation of IIP. It is important to recognize that the BAL procedure can induce an acute exacerbation of IIP.

Several reports have indicated that T cells bearing gamma delta T cell receptor (TCR) are major effector cells in mucosal immunity of the murine intestinal tract. In humans, abnormal distribution of gamma delta + T cells has also been found in inflammatory bowel diseases. We studied TCR heterodimer expressions in lymphocytes infiltrating the peripheral airways in patients with diffuse panbronchiolitis (DPB), because DPB is histologically characterized by chronic inflammation in bronchioles and could be a model for investigation of the significance of gamma delta + T cells in persistent inflammation of the human respiratory tract. Open lung biopsy specimens were obtained from 7 patients and peripheral blood lymphocytes (PBL) from 9 patients. Immunohistochemically, we detected alpha beta and gamma delta TCR by avidin-biotin complex immunoperoxidase method, utilizing BMA 031 and TCR delta 1 monoclonal antibody, respectively, PBL were analyzed by flow cytometry. Histological analysis revealed that DPB lesions mainly involved the bronchiolar walls with marked infiltration of small round cells. Many T cells were distributed in the submucosal area, although few T cells infiltrated the epithelium. Most of the T cells in the bronchioles expressed alpha beta TCR (98.7%), whereas only 1.3% expressed gamma delta TCR. There was no significant difference in the percentage of gamma delta + T cells in PBL between DPB and age- and sex-matched controls (6.7% vs. 9.1%). These results suggest that the increase of T cells bearing alpha beta TCR played a major role. However, the possibility that the decrease of T cells bearing gamma delta TCR caused reduced mucosal defense against external antigens, leading to persistent inflammation of the lower respiratory tracts in DPB, is not excluded.

A 65-year-old woman was admitted to our hospital because of pulmonary nodules, about 3 cm in diameter in the right upper lobe accompanied by pleural indentation, and 5 mm in diameter in the left middle lung field, revealed by chest X-ray. She had no clinical signs or symptoms except achalasia-like discomfort swallowing. Results of physical examinations were within normal limits. A specimen obtained from the nodule in right S2 by transbronchial biopsy showed noncaseating epithelioid granuloma containing asteroid bodies, and negative staining for acid-fast bacilli. No malignant cells were found in the specimen. Bacteriological examination of a bronchial lavage specimen was negative for pyogenic bacteria, mycobacteria and fungi. A PPD skin test was negative. BALF revealed an increase of lymphocytes and elevation of CD4/CD8 ratio. Fifteen years previously, the patient had been diagnosed as having sarcoidosis by scalene node biopsy, and had been treated with steroid therapy. Pulmonary nodules associated with pleural indentation in sarcoidosis is relatively rare, and is usually due to malignancy such as lung cancer. This possibility was ruled out clinically in the present case. Therefore, it was concluded that the pulmonary nodules in this case were due to the sarcoidosis itself.

Recently, we have reported that a nebulized solution of sodium cromoglycate (SCG) (Intal), a well known antiallergic agent, has an acute bronchodilator effect in patients with aspirin-induced asthma (AIA). Amlexanox is an antiallergic agent, with a structure similar to that of SCG. Therefore, we investigated the acute bronchodilator effect of amlexanox administered orally to adult asthmatics, focusing on a comparison between AIA and non-AIA patients. Fifteen patients participated, 8 having AIA and 7 non-AIA. After performing spirometry during remission, they were administered either amlexanox or placebo using a randomized double-blind protocol. Spirometry was then performed at 30, 60, 90 min, 2 h, and 3 h after administration. The placebo used was lactose. In the AIA group, FEV1 was significantly improved after administration of amlexanox. However, FEV1 was significantly decreased after placebo administration. On the other hand, in the non-AIA group, FEV1 was not changed after administration of either of the drugs. From these results, we conclude that amlexanox has an acute bronchodilator effect only in AIA patients.

Nitric oxide, thought to be the endothelium-derived relaxing factor (EDRF), is involved in intra- and intercellular signalling in various tissues. A system for the continuous detection of NO in the picomolar range from a perfused organ is described. The detection is based upon the chemiluminescence reaction between NO and the luminol (5-amino-2,3-dihydro-1,4-phthalazinedione)-H2O2 system. The chemiluminescence is due to the formation of peroxynitrite from NO and H2O2. The luminol-H2O2 system is specifically reactive to NO, so that other nitrogen-containing compounds, (organic nitrite, organic nitrate, and thio-nitroso compounds) or endothelium-derived compounds do not interfere. The limit of determination was approximately 100 fM. This system has been used to measure continuous NO release from isolated perfused rat kidney and the simultaneous changes of perfusion pressure. In Wistar rats basal NO release was 85 +/- 11 fmol/min-1 (g of kidney weight)-1 (39 pM in the perfusate), and acetylcholine increased NO release dose dependently with a concomitant pressure reduction. The changes in NO release were always associated with mirror image changes in the perfusion pressure. Simple pressure reduction did not interfere with the chemiluminescence. Precise titration data as well as results of some preliminary experiments using this method are presented.

To study mechanisms for attenuated endothelium-dependent vasorelaxation in hypertension, we examined the effects of acetylcholine (ACh) on renal vascular resistance (RVR) and release rates of endothelium-derived relaxing factor (EDRF) in kidneys isolated from spontaneously hypertensive rats (SHR), deoxycorticosterone acetate (DOCA) salt-hypertensive (DOCA salt) rats, and Dahl salt-sensitive (Dahl S) rats. Decreases in RVR by ACh were smaller in hypertensive rats than in their normotensive controls. The release rate of nitric oxide into the perfusate, which was estimated using nitrite-nitrate as an index, did not differ between SHR and Wistar-Kyoto rats (WKY). However, the release rate of EDRF was markedly decreased in both DOCA salt rats and Dahl S rats compared with their normotensive controls (10(-7) M ACh: DOCA salt 45 +/- 6 vs. control 410 +/- 60 pmol.min-1.g-1 kidney wt, P < 0.001). In SHR, high-K+ perfusion or pretreatment with glibenclamide, inhibitors of endothelium-derived hyperpolarizing factor (EDHF), significantly reduced ACh-induced vasorelaxation only in WKY, resulting in no differences in the RVR reduction between SHR and WKY. Thus attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF, but to a decrease in EDRF in DOCA salt rats and Dahl S rats.

A case of streptomycin-induced lupus occurring in a 48-year-old female is presented. She was admitted to our hospital in July 1990, complaining of productive cough and general fatigue. A chest roentgenogram showed cavitary lesions and infiltrative shadows in the bilateral upper and middle lung fields and a sputum smear tested positive for acid-fast bacilli. She was diagnosed as lung tuberculosis and antituberculous therapy with isoniazid, rifampicin and streptomycin was started. Ten days after starting the treatment, she began to complain of high fever and erythema on her face and forearms. Blood cell count revealed leucopenia. The antinuclear antibody and antihistone antibody were positive. The improvement of clinical findings and the lowering of antinuclear antibody titer seen after stopping streptomycin confirmed the diagnosis as streptomycin-induced lupus. Streptomycin-induced lupus is very rare.

We reported clinical features of 11 patients with Churg-Strauss syndrome (CSS). Subjects included 2 males and 9 females with a mean age of 56.3 year-old. The age of the onset of bronchial asthma was high, and most of the patients had been suffered from frequent and severe asthmatic attacks during the period preceding the vasculitis. At the onset of the disease, patients showed a variety of vasculitic symptoms, including fever and neuropathy. Peripheral blood eosinophilia was universally seen. Three patients died of heart failure or central nerve involvement. Vasculitis ameliorated in 8 cases following steroid treatment. Discontinuing maintenance therapy with low-dose steroid resulted in a relapse in only one case. The significance and indication for long-term maintenance therapy should be further clarified. Based on these findings and previous publications, the clinical characteristics of CSS in Japan are discussed.

To clarify the significance of factors of coagulation and fibrinolysis in tumor progression, we measured levels of D-Dimer, Thrombin-Anti-Thrombin III complex (TAT), and Plasmin-alpha 2-Anti-Plasmin complex (PAP) in 55 patients with primary lung cancer, and studied the relationship between these parameters and clinical TNM stage. D-Dimer, TAT and PAP increased in parallel with progression of primary tumor and distant metastasis, whereas there was no significant relationship between the progression of nodal involvement and these factors. In 19 patients, we investigated changes of D-Dimer, PAP and TAT during chemotherapy. These parameters decreased in the partial response group and minor response group, whereas they increased in the progressive disease group. These data suggest that D-Dimer, PAP and TAT determination is useful for evaluation of disorders of coagulation and fibrinolysis related to tumor progression or remission in patients with lung cancer.

Effects of risperidone (RIS, 1 mg/kg) and haloperidol (HPD, 1 mg/kg) on catalepsy, and monoamine and GABA metabolism were examined in the rats. Catalepsy was evaluated by means of a horizontal bar method. The rats were sacrificed 3 h after orally administered HPD or RIS. Levels of monoamines and their metabolites determined by HPLC-ECD, and GABA levels were determined by a radioreceptor assay. The score of catalepsy was significantly low 120 min after administration of RIS as compared to HPD. In comparison to control, HPD treatment significantly increased DOPAC in the frontal cortex, thalamus + hypothalamus, and striatum, and HVA in the striatum. In RIS-treated rats, DOPAC and HVA were significantly increased in the striatum. Moreover, RIS increased 5-HIAA in the frontal cortex, hippocampus, thalamus + hypothalamus, mid brain, pons and striatum. The concentration of GABA was unchanged in all areas of the brain after treatment with HPD, but was significantly decreased in the pons in RIS-treated rats. The present results suggested that the effects of RIS on serotonin and GABA metabolism may be related to the cause of the low potency of RIS to induce catalepsy.

Correlation dimension analysis (CDA) of spontaneous heart rate variability in humans was performed with the use of autonomic blocking agents (propranolol and atropine) and postural change, and was compared with heart rate power spectral analysis (HRPSA). The correlation dimension was increased by the suppression of sympathetic activity and decreased by the suppression of parasympathetic activity. Atropine abolished the correlation dimension and the low- and high-frequency components of HRPSA. With a postural change from supine to standing, the low- to high-frequency power ratio was significantly increased, indicating the augmentation of sympathetic activity or the reduction of parasympathetic activity, or both. Thus, it was suggested that a postural change from supine to standing causes the predominance of sympathetic activity. As this postural change decreased the correlation dimension, it was also indicated that the predominance of sympathetic activity may decrease the correlation dimension. CDA was superior to HRPSA in that the former method provided a measure of the effect of propranolol on the heart in the supine position, which could not be evaluated by the latter method. Thus, CDA of heart rate variability is a useful non-invasive tool for evaluating the autonomic balance.

Improvement in human reliability is of great concern in modern high technology systems. Efforts in the nuclear industry, mostly in Japan were surveyed and classified into improvement in human work situations and that in man-machine systems. In the former, human error prone situations were investigated using training simulators and from actual near-misses and incidents in real operating plants. The results have been used to improve operator training and other work situations. The objective of man-machine system improvement is to optimize the total performance of nuclear power plants such that automation and supervisory control by human operators will be designed to reduce human errors as well as to effectively utilize human ingenuity. Computerized operator support systems were surveyed based on the operators' role in plant operational safety. The main support functions considered here are a kind of computerization of operation manuals revised after the Three Mile Island-2 accident, and mainly supports the operators' rule-based behavior. The development of intelligent man-machine systems was then aimed at to support operators in their knowledge-based behavior to cope with unforeseen abnormal events, considering the recent advance in artificial intelligence and cognitive engineering. A case study is described.

We studied the clinical features and prognosis of 11 patients with Churg-Strauss syndrome (CSS). Subjects included 1 man and 10 women with a mean age of 56.3 years. All subjects had a history of bronchial asthma prior to the onset of CSS. It was noted that the age of onset of bronchial asthma was high, and most of the patients had suffered from frequent and severe asthmatic attacks during the periods preceding the vasculitis. Skin tests and IgE RAST revealed that less than half of the subjects were atopic. Therefore it is considered that asthmatics with late onset and severe symptoms have a high risk for CSS, and poor control of asthmatic symptoms may contribute to the onset of the vasculitis. Eleven of 12 cases including 1 patient with a relapse were treated with PSL alone (9 cases) or PSL plus cyclophosphamide (2 cases). Three patients died of heart failure or central nerve involvement. Vasculitis was ameliorated in the other cases (75%). Seven patients received maintenance therapy with low-dose of PSL (5 cases) or cyclophosphamide (2 case). None suffered from relapse of vasculitis during maintenance therapy. Discontinuation of therapy in five cases resulted in a relapse in only one case 62 months after the cessation of low-dose PSL. Although maintenance therapy appears to be useful in some CSS patients, the significance and indications for maintenance therapy should be further clarified.