Identification of a new variant of fimA gene of Porphyromonas gingivalis and its distribution in adults and disabled populations with periodontitis.

Porphyromonas gingivalis fimbriae are critical for the promotion of bacterial infection. The fimA gene encoding fimbrillin, a subunit of fimbriae, has been classified into five genotypes (types I to V) based on their nucleotide sequences. Using a fimA type-specific PCR assay, our previous study demonstrated a close relationship between P. gingivalis possessing type II and type IV fimA genes and adult periodontitis. In that study, some clinical specimens were found to be positive for both types I- and II- fimA specific primers, likely due to the coexistence of two clonal types or a single clone of an unknown genotype in the samples. In the present study, we cloned a new variant of the fimA gene, designated as type Ib fimA, from P. gingivalis HG1691. The nucleotide sequence of the cloned fimA gene showed a 97.1% homology with that of type I fimA, indicating it as a clonal variant of type I fimA. Organisms with type Ib fimA were detected in 13.5% of periodontitis patients and in 2.9% of periodontal healthy adults. Statistical analysis revealed a strong relationship between periodontitis and specific fimA types such as type Ib [odds ratio (OR) 6.51], type II (OR 77.8), and type IV (OR 7.54). Moreover, type Ib fimA-organisms were also found to be related to periodontitis in Down's syndrome (OR 1.91) and mentally disabled populations (OR 4.00). These findings suggest that P. gingivalis with type Ib fimA is closely associated with the progression of periodontitis, similar to organisms with type II and IV fimA.

Percutaneous ulnar artery approach for coronary angiography: a preliminary report in nine patients.

The radial artery approach is becoming more popular for diagnostic cardiac catheterization and interventional procedures because of its lower incidence of access site complications and decreased patient discomfort after the procedure. However, Allen's test reveals inadequate blood supply through the ulnar artery to the hand, and therefore the approach does not seem to be suitable in 10%-30% of patients. Here we demonstrated a new percutaneous ulnar artery approach for coronary angiography in nine patients. We succeeded in obtaining an entry site into the left ulnar artery in seven patients. The average time for cannulation and that for catheterization procedure were comparable with those of the radial approach previously reported from other laboratories. Complications such as bleeding, loss of an ulnar pulse, ulnar nerve injury, and the formation of an aneurysm or fistula were not observed in any patient. The ulnar approach may be another technique that decreases patient discomfort and risk, while preserving the radial artery as a potential coronary bypass graft for surgical myocardial revascularization. Cathet Cardiovasc Intervent 2001;53:410-414.

Baseline airway hyperresponsiveness and its reversible component: role of airway inflammation and airway calibre.

Airway hyperresponsiveness (AHR), in which airway inflammation has been reported to be a key factor, is an important component of asthma. However the precise role of inflammation in AHR is still unclear. In this report, airway inflammatory changes were assessed using hypertonic saline-induced sputum examination and exhaled nitric oxide analysis, and the relation between AHR to methacholine, airway calibre forced expiratory volume in one second (FEV1) and airway inflammatory indices examined. Furthermore, the changes in these variables were also examined by means of 8 weeks' open uncontrolled inhaled steroid administration (800 microg x beclomethasone x day(-1)). Asthmatic subjects had higher eosinophil counts and bradykinin concentration in induced sputum and higher exhaled NO levels, and showed AHR to methacholine. Baseline AHR significantly correlated with FEV1 but not with indices of inflammation in sputum or exhaled air. Steroid inhalation therapy was associated with a reduction in eosinophil and bradykinin concentration in sputum and NO levels in exhaled air and an improvement in FEV1 and AHR. The changes in FEV1 and AHR were significantly related to changes in markers in sputum and exhaled air (p<0.01 for each). These results suggest that baseline airway hyperresponsiveness can be predicted from the airway calibre but not from inflammatory parameters in sputum or exhaled air. In contrast, the reversible component of airway hyperresponsiveness appeared to be associated with the reduction in airway inflammation.

Response of the radial artery to three vasodilatory agents.

We examined the response of the radial artery to vasoactive agents (isosorbide dinitrate, ISDN, 1 mg, 3 mg, and 5 mg; verapamil, 1 mg, 3 mg, and 5 mg; and lidocaine, 10 mg, 30 mg, and 50 mg) in 100 consecutive patients admitted for elective coronary angiography. The drug solutions were directly injected into the radial artery from the puncture site. As a result, 5 mg of ISDN increased the diameter of the radial artery by 31% and 28.8% at the proximal and distal sites, respectively. Similarly, 5 mg of verapamil increased it by 9% and 10.8% at the proximal and distal site, respectively. But 10 mg of lidocaine decreased it by -15.6% and -12.1% at the proximal and distal site, respectively. At the doses utilized, ISDN was the most potent vasodilator for the radial artery and lidocaine caused paradoxical vasoconstriction.

Sensory nerve activation in airway microvascular permeability in guinea-pig late allergic response.

Because both bradykinin and tachykinins have a potent inflammatory action, these molecules may be involved in the late allergic response. The role of these molecules in airway microvascular permeability during the late allergic response in sensitized guinea-pigs was investigated. Three weeks after ovalbumin sensitization, the animals were pretreated with bradykinin B2 receptor antagonist HOE 140, neurokinin 1 receptor antagonist CP 96,345 or vehicle, 30 min before the ovalbumin inhalation challenge. The occurrence of the late allergic response was determined by a two-fold increase in the transpulmonary pressure from the baseline values. The microvascular permeability in the trachea was assessed by an index defined as the ratio of the area of vasculature labelled by Monastral blue dye (area density %). Significant microvascular permeability and eosinophil accumulation were observed during the late allergic response. Both the bradykinin and substance P concentrations in the bronchoalveolar lavage fluid were increased during the late allergic response. Pretreatment with HOE 140 suppressed the substance P elevation. Both HOE 140 and CP 96,345 also inhibited the airway microvascular permeability during the late allergic response without affecting the eosinophil accumulation in the airways. These findings suggest that bradykinin-mediated sensory nerve activation may play a role in microvascular permeability during the late allergic response in guinea-pigs.

Role of peroxynitrite in airway microvascular hyperpermeability during late allergic phase in guinea pigs.

We investigated the role of peroxynitrite, which is formed by a rapid reaction between nitric oxide (NO) and superoxide anion (O(2)(-)), in the airway microvascular hyperpermeability during the late allergic response (LAR) in sensitized guinea pigs in vivo. The occurrence of LAR was assessed as a 100% increase in the transpulmonary pressure, which was monitored by the esophageal catheter technique. Airway microvascular permeability was assessed by Monastral blue dye trapping between the endothelium using an image analyzer. In the LAR phase (4 to 6 h after antigen inhalation), microvascular hyperpermeability and eosinophil infiltration within the airway wall were observed. NO production and xanthine oxidase (XO)/xanthine dehydrogenase activity, which are responsible for O(2)(-) production, were enhanced during the LAR. Peroxynitrite formation assessed by nitrotyrosine immunostaining was also exaggerated at that time. The microvascular hyperpermeability during the LAR was largely reduced by NO synthase inhibitor (L-NAME, 72.7% inhibition; p < 0.05), XO inhibitor (AHPP, 60.8% inhibition; p < 0. 05) and peroxynitrite scavenger (ebselen, 81.0% inhibition; p < 0. 05). L-NAME had a small but significant inhibitory effect on airway eosinophil accumulation, but AHPP and ebselen had no effect. These results suggest that excessive production of O(2)(-) and NO occurs in the LAR. These two molecules appear to cause airway microvascular hyperpermeability via peroxynitrite formation.

Induction of nitric oxide synthase by lipopolysaccharide inhalation enhances substance P-induced microvascular leakage in guinea-pigs.

Inducible nitric oxide (NO) synthase (iNOS)-mediated hyperproduction of NO in airways has been reported in asthmatic patients. However, the role of NO in the pathogenesis of asthma has not yet been fully elucidated. The aim of this study was to examine whether the iNOS-derived NO affects airway microvascular leakage, one of the characteristic features of asthmatic airway inflammation. Guinea-pigs were exposed to lipopolysaccharide (LPS) (1 mg x mL(-1)) by inhalation in order to induce iNOS in the airways, and the histochemical staining of reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase activity was determined 5 h after the inhalation to confirm the iNOS induction. Airway microvascular leakage to subthreshold doses of substance P (0.3 microg x kg(-1), i.v.) was also examined in the absence and presence of an iNOS inhibitor (aminoguanidine) in LPS- or saline-exposed (control) animals using Evans blue dye and Monastral blue dye. In the LPS-exposed animals, increased NADPH-diaphorase activity was observed in the airway microvasculature compared with the control animals. Substance P caused significant airway microvascular leakage assessed by Evans blue dye in all airway levels in the LPS-exposed animals but not in the control group. This was also confirmed by Monastral blue dye extravasation. Aminoguanidine abolished this LPS-induced enhancement of plasma leakage to substance P without changing the systemic blood pressure. These results may suggest that inducible nitric oxide synthase-derived nitric oxide is capable of potentiating neurogenic plasma leakage in airways.

Relationship between cholinergic airway tone and serum immunoglobulin E in human subjects.

It has recently been shown that immunoglobulin (Ig)E facilitates the cholinergic bronchoconstrictor pathway in human tissue in vitro. However, whether this occurs in humans in vivo has not been clarified. In this study, the bronchodilator responses were examined to inhalation of a submaximal dose of the anticholinergic agent oxitropium bromide (600 microg) in normal and allergic subjects with various levels of total serum IgE. Values of the forced expiratory volume in one second (FEV1) for all subjects were greater than 80% of predicted, but were negatively correlated with serum IgE levels (p<0.01). Oxitropium bromide inhalation induced an increase in FEV1 that was significantly greater in allergic rhinitis patients with high serum IgE (155+/-20 mL (mean+/-SEM), p<0.05) than in healthy subjects (64+/-21 mL) or those with allergic rhinitis but low serum IgE (82+/-21 mL, p<0.05). In contrast, the effects of the inhaled beta2-adrenergic agent orciprenaline sulphate (2.25 mg) were not significantly different among the three groups. In conclusion, higher serum immunoglobulin E levels were correlated with lower values of the forced expiratory volume in one second, and anticholinergic agents, but not beta2-adrenergic agents, caused more pronounced bronchodilation in subjects with high than in those with low immunoglobulin E levels. These data suggest that serum immunoglobulin E may be one of the factors that determine the airway tone, possibly via cholinergic mechanisms.

Impairment of neural nitric oxide-mediated relaxation after antigen exposure in guinea pig airways in vitro.

Nitric oxide (NO), a neurotransmitter of inhibitory nonadrenergic noncholinergic (iNANC) nerves in airways, is a radical with a short half-life, and its function may be modified by airway inflammation. To test this hypothesis, we examined whether airway allergic inflammation affects iNANC responses mediated by NO in guinea pigs in vitro. Animals sensitized with ovalbumin (OA) were challenged with 0.03% OA (OA group) or saline (saline group) by inhalation on 3 consecutive days. On the day after the final challenge, iNANC responses elicited by electrical field stimulation (2 to 16 Hz) or relaxation responses to 3-morpholinosydnonimine (SIN-1), 10(-8) to 10(-4) M, were obtained in the tracheal strips precontracted by histamine (3 x 10(-6) M) in the presence of atropine and propranolol (both 10(-6) M). The INANC responses of the OA group were significantly attenuated compared with those of the saline group (p < 0.05), and the inhibitory effect of a NO synthase (NOS) inhibitor, Nm-nitro-L-arginine methyl ester, on the INANC responses was abolished in the OA group. SIN-1-induced tracheal smooth muscle relaxation was also significantly affected by antigen exposure (p < 0.05), the effect of which disappeared in the presence of a NO scavenger, carboxy PTIO (3 x 10(-6) M). The impairment of the INANC responses after antigen exposure was significantly restored by superoxide dismutase (1,000 U/ml), especially at lower frequencies. Histochemical demonstration of NADPH-diaphorase-positive nerves representing neural NOS density was not different between the two groups. These results suggest that allergic airway inflammation impairs neural NO-induced relaxation, presumably by inhibiting the access of neural NO to the airway smooth muscle.

Role of endogenous nitric oxide in airway microvascular leakage induced by inflammatory mediators.

This study examines the role of endogenous nitric oxide (NO) in airway microvascular leakage induced inflammatory mediators, which play an important role in asthmatic airways. Guinea-pigs were anesthetized and mechanically-ventilated with monitoring of arterial blood pressure, and airway microvascular leakage induced by intravenous injection of substance P (SP), leukotriene D4 (LTD4) and histamine was evaluated using Evans blue dye and Monastral blue dye in the presence and absence of the NO synthase inhibitors, L-NG-nitroarginine methyl ester (L-NAME) and L-NG-monomethyl arginine (L-NMMA). The effect of a soluble guanylate cyclase inhibitor, LY83583, on SP-induced dye leakage was also examined. Intravenous injection of SP (1 microgram.kg-1), LTD4 (1 microgram.kg-1) and histamine (100 micrograms.kg-1) significantly increased dye extravasation at all airway levels. Pretreatment with L-NAME (10 mg.kg-1 i.v.) and L-NMMA (100 mg.kg-1 i.v.) significantly inhibited SP-induced extravasation, and L-arginine (100 mg.kg-1 i.v.) reversed L-NAME-induced inhibition. L-NAME (10 mg.kg-1 i.v.) also significantly inhibited LTD4-induced dye extravasation only in central airways, and this inhibitory effect was abolished by a neurokinin-1 (NK1) antagonist, FK888 (10 mg.kg-1 i.v.) pretreatment. Histamine-induced dye extravasation was not affected by L-NAME. LY83583 (2.5 and 7.5 mg.kg-1 i.v.) partially but significantly reduced SP-induced dye leakage. These results suggest that endogenous nitric oxide plays a role in neurokinin-1 receptor-mediated airway microvascular leakage, and presumably involves the guanylate cyclase pathway.

Endogenous nitric oxide modifies antigen-induced microvascular leakage in sensitized guinea pig airways.

To examine the role of endogenous nitric oxide in allergic airway inflammation, we investigated the effect of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (l-NAME), on antigen-induced airway microvascular leakage in actively sensitized guinea pigs by using Evans blue dye. Three weeks after sensitization with ovalbumin (10 micrograms), the tracheas were cannulated, and lungs were artificially ventilated. Animals were pretreated with atropine and propranolol (both 1 mg/kg, intravenously) to avoid neural modification. Ovalbumin inhalation (3 mg/ml, 1 minute) challenge caused significant microvascular leakage in all airways portions, which was significantly suppressed in a dose-dependent manner by pretreatment with intravenous injection of L-NAME (1 and 10 mg/kg) but not with the inactive enantiomer D-NAME (10 mg/kg). This inhibition by L-NAME was significantly reversed by co-administration of L-arginine (100 mg/kg, intravenously). Pretreatment with a vasoconstrictor, phenylephrine (20 micrograms/kg, intravenously), had no inhibitory effects on antigen-induced airway microvascular leakage despite increasing systemic blood pressure. Inhalation of representative mast cell-derived mediators, histamine (2 mg/ml, 1 minute) or leukotriene D4 (5 micrograms/ml, 1 minute), produced significant microvascular leakage in all airways. L-NAME (10 mg/kg, intravenously) partially but significantly inhibited leukotriene D4-induced leakage, whereas histamine-induced leakage was not affected. These results suggest that endogenous nitric oxide acts to increase airway microvascular leakage after airway allergic reaction.

Allergic airway response and potassium channels: histamine release and airway inflammation.

The possible involvement of potassium (K) channels in allergic airway responses was examined in ovalbumin (OA)-sensitized guinea pigs. An ATP-sensitive K channel opener (BRL-38227) inhibited OA inhalation-induced bronchoconstriction and airway plasma leakage. BRL-38227 also had an inhibitory effect on exogenous histamine- and leukotriene-induced responses. In contrast, BRL-38227 did not affect OA-induced histamine release from minced lung tissues. Therefore, the ATP-sensitive K channel opener inhibits allergic bronchoconstriction and plasma leakage as a result of its effect on airway smooth muscle and postcapillary venules. Apamin, a small conductance Ca2+ -activated K channel (PK,Ca) blocker, significantly inhibited both OA-induced tracheal contraction and histamine release from lung tissues, suggesting that this compound reduces allergic airway responses via a mast cell stabilizing effect. We conclude that ATP-sensitive K channel opening and small conductance PK,Ca closure may be beneficial for preventing allergic airway responses.

[Analysis of the preceding R-R interval and the coupling interval on premature ventricular contractions].

Premature Ventricular Contractions (PVCs) are one of the common arrhythmias. Although the analysis of the preceding R-R interval and the coupling interval on the Holter electrocardiogram, the Lorenz plotting method, has been used to characterize mature of PVC, this analysis has typically been performed without regard to the morphological classification of the electrocardiogram waveforms. Therefore, we performed the Lorenz plotting after a PVC classification. We analyzed 45 cases with more than 1,000 PVCs per day. Twenty-six of the cases with PVCs had no organic heart disease (idiopathic PVC); nineteen of the cases with PVCs had organic heart disease (PVC with disease). Each R-R interval was analyzed after classification based on the morphology of each QRS wave of the PVC. The computer generated a two-dimensional plot of the relationship between the preceding R-R interval of PVC and the following coupling interval. The forms of PVCs were monoform in idiopathic PVC and were mostly multiform in PVC with disease. The patterns on Lorenz plotting in idiopathic PVC had a tendency to be uniform with small standard deviations. In contrast, multiform PVCs tended to be highly variable with large standard deviations. The value of SD was 32.1 +/- 12.0 msec in idiopathic PVC, and that of the slope "a" was 0.048 +/- 0.051 in PVC with disease. Using the SD values and the slope "a" values, we were able to classify idiopathic PVC vs. PVC with disease with a 95% sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Multi-institutional study of all-trans-retinoic acid as a differentiation therapy of refractory acute promyelocytic leukemia. Leukaemia Study Group of the Ministry of Health and Welfare.

We treated 70 acute promyelocytic leukemia (APL) patients with daily oral 45 mg/m2 all-trans-retinoic acid (ATRA) in two multi-institutional prospective studies. Of 64 evaluable patients, 21 were refractory to initial induction chemotherapy; 10 were refractory to salvage chemotherapy; 17, five, and four were in the first, second and, third relapse, respectively; and seven were previously untreated due to old age. In the first study with ATRA from China, 18 out of 22 (82%) evaluable patients achieved complete remission (CR). Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01); < 100/microliters in 17 out of 18 CR cases, and > or = 200/microliters in all failure cases. In the second study with ATRA from Hoffmann-La Roche, if initial leukemia cell counts were more than 200/microliters, chemotherapy was first given and then ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. Morphological evidence of differentiation was noted in all CR cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 20-month predicted disease-free survival rate is 76% for cases achieving their first CR with ATRA. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage, and high serum triglyceridemia.

Differentiation of transiently ischemic from infarcted myocardium by thallium-201 exercises scintigram after active ergometer rehabilitation.

It has been frequently reported that while myocardial viability is neglected in conventional methods of diagnosis such as left ventriculography, ECG, and exercise thallium-201 myocardial scintigraphy (Ex-Tl), revascularization often results in improving left ventricular wall motility. In the present study, the authors contrived a method to accurately evaluate the viability of the myocardium by means of exercise rehabilitation, and tested the method in clinical cases. Among patients with myocardial infarction, we selected a patient with negative viability in the diseased area as determined by chronic ECG, left ventriculography (LVG), coronary angiography and Ex-Tl. This patient went through two weeks of active exercise rehabilitation gauged with an ergometer, and was then re-examined by Ex-Tl. After the evaluation, revascularization was performed for the patient who demonstrated viability of the infarcted myocardium in EX-Tl after rehabilitation, and significant improvement in contractility was shown in the chronic LVG. These findings indicate that our method of detecting potential viability of the infarcted myocardium is of clinical significance.

Long-time inflation of the PTCA balloon.

For patients for whom the conventional percutaneous transluminal coronary angioplasty (PTCA) did not adequately improve stenosis, or sufficient angioplasty was impossible because of occurrence of dissection, we attempted using a long-time balloon inflation for more than 10 minutes. In order to allow the use of this balloon, we instituted an active rehabilitation program using a bicycle ergometer to promote the development of the collateral circulation up to the time of performing diagnostic angiography and PTCA, while attempting to use a perfusion balloon catheter for those patients not developing sufficient collateral circulation. Of the 134 patients undergoing PTCA, unsatisfactory angiographic results were obtained in 13 patients. Of these patients, long-time balloon inflation was performed in seven and primary success was achieved in six. From this study, we believe that the long-time balloon inflation in PTCA can improve the primary success rate and reduce postoperative complications.

[A case of giant cell myocarditis associated with a progressive disturbance in the conduction system].

A 73 year old male patient with a history of pulmonary tuberculosis was admitted to our department because of dyspnea and abdominal pain. The chest X-ray film on admission showed bilateral lung congestion. The ECG showed atrial fibrillation, left axis deviation and incomplete right bundle branch block. Five days after admission, the ECG changed into sinus rhythm and complete right bundle branch block. Eight days after admission, the patient complained of chest pain and the ECG showed ST elevation in II, III, aVF, reciprocal ST depression in V, and complete A-V block with junctional rhythm. Emergency coronary angiography revealed no significant stenosis. Echocardiography showed reduced contraction of the inferior wall and diffuse granular echoes in the myocardium. Light microscopic study revealed fibrosis, infiltration of eosinophils and histiocytes, degenerated myocardium and multinucleated giant cells. Some of the giant cells were morphologically similar to myocardium, so the myocardium might be a place of immunological reaction.

[A case of aortitis syndrome].

A 57 years old woman was admitted for the investigation of anginal chest pain. Her coronary angiography didn't show any typical finding seen in the aortitis syndrome, but coronary sclerosis and stenosis seen in the usual atherosclerotic patients. The cerebral angiography was performed, too. The right vertebral artery, which was tortuous and dilated, was seen, but the other three cerebral vessels were not seen. These rare findings were reported in this report. We added the discussion about the relation between the aortitis syndrome and angina pectoris.

[Multiple liver abscesses due to Candida albicans in a patient with acute promyelocytic leukemia: percutaneous transhepatic intraportal administration of amphotericin B].

A 36-year-old male with acute promyelocytic leukemia in second relapse was admitted to receive reinduction therapy in June, 1985, and entered into third complete remission, but he developed spiky fever after chemotherapy. Ultrasonic tomography revealed multiple liver abscesses and culture of the aspirates demonstrated Candida albicans in the abscesses. He was treated with intravenous administration of amphotericin B (AMPH-B) but the effect on the liver abscesses was unsatisfactory and consolidation therapy was difficult to start. AMPH-B (30 mg/day) was administered by percutaneous transhepatic intraportal administration (PTIA). About two months later, multiple liver abscesses disappeared. No remarkable complications such as severe fever, chill and renal dysfunction were recognized during PTIA of AMPH-B. So PTIA of AMPH-B is considered to be useful and safe for the management of fungal liver abscesses.