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Biomedical subjects

H Kawada

Publications and source records attributed to H Kawada.

At least 55 records · Page 3Linked to original sources

Interactions of plaunotol with bacterial membranes.

Plaunotol, a cytoprotective antiulcer agent, has a bactericidal effect against Helicobacter pylori, which may result from interaction of this compound with the bacterial cell membrane. The purpose of the present study was to confirm that plaunotol interacts with the H. pylori membrane. Membrane fluidities were measured using two stearic acid spin labels, namely 5-doxyl-stearic acid (in which the nitroxide group is located in the upper portion of the bacterial cell membrane) and 16-doxyl-stearic acid methyl ester (in which the nitroxide group is located deeper in the bacterial cell membrane), by means of electron spin resonance. The membrane fluidities of plaunotol-treated cells were significantly increased in the measurements made using the two spin labels. We also attempted to isolate plaunotol-resistant H. pylori in vitro by two different methods. To assess the level of resistance that could be reached, H. pylori was passaged five times on an agar plate containing subinhibitory concentrations of plaunotol or metronidazole. To measure the rate of development of resistance, H. pylori was grown with subinhibitory concentrations (0.25 x MIC) of plaunotol or metronidazole, and quantitatively plated on to medium containing 4 x MIC of the compounds. This treatment was repeated once more. No plaunotol-resistant colonies were selected by the two methods. H. pylori developed resistance to metronidazole easily and at a relatively high rate. The mechanism by which plaunotol directly fluidizes and destroys the H. pylori membrane might make it difficult for this organism to develop resistance to plaunotol. It was confirmed that the bactericidal effects of plaunotol were also shown against Staphylococcus aureus, Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxella catarrhalis and Haemophilus influenzae. No such effect was seen against Escherichia coli and Pseudomonas aeruginosa.

Anti-Bacterial Agents↗

Delayed healing of chronic gastric ulcer after Helicobacter pylori infection in mice.

It has been suggested that there is a close relationship between Helicobacter pylori and the onset or recurrence of gastroduodenal disease. The aim of this study was to examine the effect of H. pylori on the healing of chronic gastric ulcers induced in mice. H. pylori administered to nude mice delayed the healing of experimental acetic acid-induced gastric ulcers. Histological examination showed the occurrence of high densities of H. pylori on the surface of epithelial cells and in the ulcerated area. Repeated administration of amoxicillin (10 mgkg(-1) daily for 5 days) eradicated H. pylori and increased the rate of healing of gastric ulcers in H. pylori-infected mice, but metronidazole, which also eradicated the organisms, did not significantly affect the rate of healing. In conclusion, H. pylori-infection delayed the healing of gastric ulcers induced by the serosal application of acetic acid in mice, possibly by aggravation or prolongation of the mucosal inflammation. Amoxicillin eradicated H. pylori and promoted gastric ulcer healing in mice infected with H. pylori.

Amoxicillin↗

Efficacy of CS-834 against experimental pneumonia caused by penicillin-susceptible and -resistant Streptococcus pneumoniae in mice.

The efficacy of CS-834, a novel oral carbapenem, was assessed by using a murine model of pneumonia caused by penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae and was compared with those of oral cephems, i.e., cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil. Intranasal inoculation of 10(6) CFU of penicillin-susceptible or penicillin-resistant S. pneumoniae in the exponential growth phase induced pneumonia and bacteremia in ddY mice within 48 h. For the treatment of infections caused by the penicillin-susceptible strain the antibiotics were administered orally at 0.4, 2, and 10 mg/kg of body weight twice daily for 2 days beginning at 24 h after bacterial inoculation, and for the treatment of infections caused by a penicillin-resistant strain the antibiotics were administered at 2, 10, and 50 mg/kg twice daily for 2 days beginning at 24 h after bacterial inoculation. Among the antibiotics tested, CS-834 exhibited the most potent efficacy against both types of strains. Against infections caused by penicillin-susceptible S. pneumoniae, CS-834 at all doses significantly reduced the numbers of viable cells in both the lungs and blood. Cefpodoxime proxetil at all doses and cefteram pivoxil and cefditoren pivoxil at doses of 2 and 10 mg/kg showed comparable efficacies. Against infections caused by penicillin-resistant S. pneumoniae, CS-834 at doses of 10 and 50 mg/kg showed the most potent efficacy among the antibiotics tested, resulting in the maximum decrease in the numbers of viable cells in the lungs. Comparable efficacies were observed with cefteram pivoxil and cefpodoxime proxetil at doses of 50 mg/kg each. The concentration of CS-834 in the lungs and blood was higher than that of cefdinir and was lower than those of the other antibiotics tested, suggesting that the potent therapeutic efficacy of CS-834 reflects its strong activity against S. pneumoniae.

Animals↗

A novel variant of B-lymphoid leukemia expressing kappa/lambda light chains.

We studied a patient with an indolent leukemia which behaved similarly to chronic lymphocytic leukemia (CLL). Leukemic cells, however, showed larger cell diameters and lower nuclear/cytoplasmic ratios than typical CLL cells, and contained numerous cytoplasmic vacuoles. The cells also demonstrated some morphologic characteristics of hairy cell leukemia. Furthermore, flow-cytometric analysis demonstrated a distinct population of kappa/lambda double-positive tumor cells, as well as kappa single and lambda single populations. Southern blot analysis confirmed rearranged bands for both light chains with a monoclonal heavy chain rearrangement. Despite a decision not to treat this asymptomatic patient, disease progression was not observed. This case may represent a unique variant of B lymphoid leukemia. Possible mechanisms of abnormal light chain expression are discussed.

Aged↗

A case of variant angina pectoris with similar findings on both rest and matched exercise thallium-201 studies.

A patient with variant angina showed similar findings on both the rest and matched exercise 201Thallium (201Tl) myocardial perfusion scintigrams. The 65-year old man was admitted to hospital because of rest angina. His electrocardiogram during the attack disclosed ST segment elevation on inferior leads. However, emergency coronary arteriogram showed no fixed stenosis. Intracoronary injection of acetylcholine induced a spasm on the distal right coronary artery, but not in the left coronary artery. In the rest 201Tl study, septal perfusion was low on the early image, although partial redistribution of this site was observed on the delayed image without the appearance of chest pain or electrocardiographic ischemic change. Similary, in the 201Tl exercise study undergone 2 weeks later, septal redistribution was diagnosed because the early image had decreased septal perfusion. Both the exercise 123I-metaiodobenzylguanidine study and the rest 123I-betamethyl-p-iodophenyl-pentadecanoic acid study showed inferior abnormalities on the early and delayed images. Although a coronary spasm was not induced in the left anterior descending artery with the acetylcholine test, septal redistribution was observed on the delayed image of both the rest and exercise 201Tl studies. The mechanism of the redistribution on the rest 201Tl study was unclear.

Aged↗

[Usefulness of intracoronary injection of acetylcholine and ergonovine in patients with variant angina].

The correlation was examined between the angina-producing arteries predicted to be responsible for the sites of ST segment elevation during spontaneous ischemic attacks and the arteries in which spasm was induced by intracoronary injection of either acetylcholine or ergonovine in patients with variant angina. From 1991 January to 1996 June, 42 patients with variant angina, 40 men and 2 women with a mean age of 61.6 years old, underwent the acetylcholine provocation test within 2 weeks of observation of the last ST segment elevation. After discontinuation of antianginal agents for at least 24 hours, a bolus of acetylcholine was injected in incremental doses of 20, 50 micrograms (occasionally 80 micrograms) into the right coronary artery and of 20, 50 and 100 micrograms incrementally into the left coronary artery to provoke coronary spasm. Intracoronary injection of ergonovine was added in nine patients, in whom intracoronary injection of acetylcholine failed to document coronary spasm on the arteries predicted to be responsible for the sites of ST segment elevation during anginal attacks. Ergonovine was injected in total doses of 40 micrograms into the right coronary artery and of 64 micrograms into the left coronary artery. Positive spasm was defined as induction of more than 99% reversible stenosis. The correlation between the arteries predicted to be responsible for the sites of ST segment elevation during attacks and the vessels in which spasm was induced by acetylcholine test was 78.6% for all patients and 80.0% for all sites of ST segment elevation. By adding the ergonovine test after the acetylcholine test, the correlation increased to 95.2% for all patients and 95.6% for all sites of ST segment elevation. The correlation observed agrees with previous studies in which the ergonovine test was performed in patients without induced spasm by intracoronary injection of acetylcholine and that the super-imposed ergonovine test is useful for diagnosing patients with variant angina.

Acetylcholine↗

[Usefulness of thallium-201 myocardial scintigraphy during hyperventilation and accelerated exercise test in patients with vasospastic angina and nearly normal coronary artery].

The usefulness of thallium-201 (201Tl) myocardial scintigraphy was studied in 109 patients with vasospastic angina who had nearly normal coronary arteries (degree of stenosis < 50%). Coronary spasm was confirmed by pharmacologic agents in all 109 patients from January 1991 to June 1996. The appearance rate of visual redistribution on 201Tl myocardial scintigraphy was compared between four groups, 34 patients performing graded bicycle ergometer exercise starting at a work load of 50 W with increments of 25 W every 3 min [Ergo (3) group], 14 patients performing hyperventilation for 5 min [HV (5) group], 31 patients performing bicycle ergometer exercise with increments of 25 W every 1 min after 5 min hyperventilation [HV (5) + Ergo (1) group], and 30 patients at rest (Rest group). The value of the visual redistribution rate on 201Tl myocardial scintigrams in the HV(5) + Ergo (1) group (65%) was higher than that in the patients of other groups [Ergo (3) 41%, HV (5) 43%, Rest 33%]. However, there were no significant differences between the four groups. Stress 201Tl imaging after hyperventilation and accelerated exercise is useful to disclose ischemic evidence in about two thirds of patients with vasospastic angina and nearly normal coronary arteries, whereas about 40% of patients had visual redistribution on 201Tl myocardial scintigrams by performing standard procedures.

Acetylcholine↗

[Characteristics of spasm-induced vessels in patients with vasospastic angina and a history of syncope].

One hundred and eighty-seven consecutive patients with vasospastic angina and coronary spasm provoked by intracoronary injection of acetylcholine and/or ergonovine were treated from January 1991 to June 1997. Fifteen of these patients, 14 men and one woman (mean age of 63 years old), had a history of syncope. There were no significant differences in the distribution of induced spasm vessels, single spasm vs multiple spasms, variant angina pectoris and organic stenosis (< 75%) between patients with and without a history of syncope. There were no significant differences concerning the distribution of the sites of induced spasm in the circumflex artery and left anterior descending artery between the two groups. However, coronary spasm in the proximal portion of the right coronary artery (segment 1 or 2 according to the functional classification of American Heart Association) occurred more frequently in patients with a history of syncope [80.0% (12/15) vs 45.3% (78/172); p < 0.05]. Twelve of the 96 patients with coronary spasm in the proximal portion of the right coronary artery had a history of syncope, so these patients require careful management.

Acetylcholine↗

[Reinfection tuberculosis at a day-laborers' facility equipped with a sauna].

Restriction-fragment-length polymorphism (RFLP) analysis was used to study one outbreak of reinfection pulmonary tuberculosis at a day-laborers' facility equipped with a sauna. The results were interpreted in conjunction with clinical and epidemiologic data. The DNA prove was derived from the insertion sequence IS 6110. A 63-year-old man who stayed at a day-laborers' facility for eight months was found to have advanced cavitary lung disease with sputum smears strongly positive for acid-fast bacilli. One year later a 46-year-old man staying at the same facility for 24 months was also found to have sputum-positive tuberculosis. The 46-year-old man had undergone treatment for tuberculosis 16 years previously and showed radiographic evidence of previous lung damage from tuberculosis. The second man had no tubercule bacilli in sputum when the 63-year-old man was found to have sputum-positive tuberculosis. The organisms isolated from these two men were both drug sensitive and had a similar RFLP pattern which suggests that 63-year-old man was the source of this outbreak and that pulmonary tuberculosis in the 46-year-old man was caused by exogenous reinfection. We conclude that exogenous reinfection may have been one pattern of tuberculosis transmission in this high-risk environment.

DNA, Bacterial↗

[Familial pulmonary arteriovenous malformation diagnostic of the Osler-Weber-Rendu disease].

A 53-year-old woman was admitted to the hospital for investigation of an abnormal shadow in the middle lobe of the right lung on a chest X-ray film. The filling of most of the shadowed area with contrast media on a chest CT scan suggested a vascular lesion. Further investigation by intravenous digital subtraction angiography and color doppler sonography led to the diagnosis of pulmonary arteriovenous malformation. An abdominal CT scan suggested the presence of an arteriovenous malformation in the liver, and a bronchoscopic study revealed telangiectatic lesions on the laryngeal mucosa. The patient's father had died at the age of 61, due to intracranial bleeding, which suggested he might have had an arteriovenous malformation in the brain. The patient's daughter has a pulmonary arteriovenous malformation. This family of vascular malformation indicates that the patient had Osler-Weber-Rendu disease. Osler-Weber-Rendu disease is an autosomal-dominant inherited disorder that may give rise to arteriovenous malformations, mainly in the lungs and the brain. We found that color doppler sonography can be useful for the diagnosis of pleural-based pulmonary arteriovenous malformation.

Adult↗

[Clinical differences between variant and non-variant angina pectoris].

The differences in clinical characteristics were studied between variant angina pectoris with ST segment elevation during ischemic attacks and non-variant angina pectoris without ST segment elevation. Spasm provocation test was performed with either acetylcholine or ergonovine in 192 consecutive patients with vasospastic angina from January 1991 to June 1997. Thirteen patients were excluded because of insufficient data. Fifty-five patients had variant angina and 124 patients had non-variant angina. Coronary risk factors, serum cholesterol level, triglyceride level, high-density lipoprotein cholesterol level, history of syncope, the rates of second or third atrioventricular block and ventricular tachycardia or fibrillation, the incidence of organic stenosis (> or = 50%), the number of vessels with provoked spasm, the dose of acetylcholine and ergonovine used, and duration from the first appearance of chest pain were compared between the 2 groups. Patients with variant angina had more fixed stenosis (p < 0.01), required more percutaneous transluminal coronary angioplasty procedures, lower doses of intracoronary administration of acetylcholine for the induction of coronary arterial spasm and shorter duration from the first appearance of chest pains (p < 0.01) than patients with non-variant angina. However, there were no differences in other factors between the 2 groups. Variant angina pectoris has the same clinical characteristics as non-variant angina pectoris, although variant angina tends to cause higher spasmophilic activity and more fixed stenosis.

Acetylcholine↗

[Tuberculosis of the central nervous system experienced at the International Medical Center of Japan].

In spite of recent advances in diagnosis and chemotherapy of tuberculosis, prognosis of tuberculosis of the central nervous system (CNS) is still poor. We evaluated clinical characteristics of 14 patients with the CNS tuberculosis (10 male and 4 female, 21 to 71 years of age) who were hospitalized at IMCJ from 1988 to 1997. Twelve patients had tuberculous meningitis (2 of them had also intracranial tuberculoma), 1 had intracranial tuberculoma and 1 had spinal cord tuberculosis. For the acid-fast bacilli, the smears of cerebrospinal fluids (CSF) were all negative but the cultures for M. tuberculosis were positive in 5. Using PCR method, M. tuberculosis was identified from CSF specimens in 2 out of 9 culture negative patients, thus suggesting the usefulness of the PCR for the rapid diagnosis of CNS tuberculosis. The adenosine deaminase (ADA) levels in CSF may provide another diagnostic clue because they were elevated in 8 out of 10 cases. It is to be noted that there were three patients who developed clinical manifestations of CNS tuberculosis after the initiation of chemotherapy for pulmonary tuberculosis. In the last five cases, four-drug regimen which included PZA, was used with a good result. The success could be related to the addition of PZA which penetrates blood-brain barrier just as good as INH. Two patients died and one remains unconscious with severe neurological sequelae. The present study indicates that positive CSF culture, hydrocephalus and consciousness disturbance are important factors in determining poor prognosis of the CNS tuberculosis.

Adult↗

[Absence of induced spasm by intracoronary injection of 50 micrograms acetylcholine in the right coronary artery: usefulness of 80 micrograms of acetylcholine as a spasm provocation test].

This study investigated whether the maximal dose of 50 micrograms acetylcholine for the induction of coronary spasm in the right coronary artery is adequate. The acetylcholine test was performed in 388 consecutive patients to evaluate spasm from January 1994 to December 1997. Coronary spasm in the right coronary artery was induced in 43 patients, 37 men and 6 women with a mean age of 63 +/- 8 years by intracoronary injection of 80 micrograms of acetylcholine rather than 50 micrograms. These included 15 patients (35%) with rest angina, 23 patients with ischemic heart disease other than rest angina and 5 patients (12%) with non-ischemic heart disease. Acetylcholine was injected in incremental doses of 20, 50 and 80 micrograms into the right coronary artery. Positive spasm was defined as induction of more than 90% reversible narrowing associated with either usual chest pain or ischemic electrocardiographic changes. Clinical and angiographical characteristics was studied in these patients. Fifteen (35%) patients had rest angina and 4 patients had variant angina with ST elevation in the inferior leads. Two thirds of the patients had coronary spasm in the distal portion of the right coronary artery and one third of those disclosed spasm focally. Coronary spasm was induced in 38 (15%) of 246 patients with ischemic heart disease and in 5 (4%) of 142 patients with non-ischemic heart disease. The prevalence of positive spasm in patients with ischemic heart disease was significantly higher (p < 0.01) than in patients with non-ischemic heart disease. A dose of 80 micrograms of acetylcholine, more than the maximal standard dose, might be clinically useful for the induction of spasm in the right coronary artery if coronary spasm of this artery is strongly suspected.

Acetylcholine↗

[Diagnosis of pulmonary tuberculosis by the amplicor test for Mycobacterium tuberculosis in induced sputum].

The polymerase chain reaction (PCR) technique was compared with the conventional smear and culture method for the detection and identification of Mycobacterium tuberculosis in 25 induced sputa samples. Sputum induction was performed with an ultrasonic nebulizer using 3% hypertonic saline in 27 previously untreated patients suspected of active pulmonary tuberculosis clue to chest X-ray findings, but who were unable to spontaneously expectorate sputum. All patients received anti-tuberculosis drugs for at least 6 months after sputum induction. Two patients could not expectorate sputum after hypertonic saline inhalation. Microscopy failed to detect positive acid-fast bacilli in 25 induced sputa samples. Induced sputa were both PCR- and culture-positive for 10 patients, PCR-positive and culture-negative for 4 patients, and PCR-negative and culture-positive for 2 patients. These results suggest that the PCR method is useful in diagnosing tuberculosis in induced sputum, and that the results of PCR and culture Procedures can complement each other.

Adolescent↗

In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem.

CS-834 is a novel oral carbapenem antibiotic. This compound is an ester-type prodrug of the active metabolite R-95867. The antibacterial activity of R-95867 was tested against 1,323 clinical isolates of 35 species and was compared with those of oral cephems, i.e., cefteram, cefpodoxime, cefdinir, and cefditoren, and that of a parenteral carbapenem, imipenem. R-95867 exhibited a broad spectrum of activity covering both gram-positive and -negative aerobes and anaerobes. Its activity was superior to those of the other compounds tested against most of the bacterial species tested. R-95867 showed potent antibacterial activity against clinically significant pathogens: methicillin-susceptible Staphylococcus aureus including ofloxacin-resistant strains, Streptococcus pneumoniae including penicillin-resistant strains, Clostridium perfringens, Neisseria spp., Moraxella catarrhalis, most members of the family Enterobacteriaceae, and Haemophilus influenzae (MIC at which 90% of strains are inhibited, < or =0.006 to 0.78 microg/ml). R-95867 was quite stable to hydrolysis by most of the beta-lactamases tested except the metallo-beta-lactamases from Stenotrophomonas maltophilia and Bacteroides fragilis. R-95867 showed potent bactericidal activity against S. aureus and Escherichia coli. Penicillin-binding proteins 1 and 4 of S. aureus and 1Bs, 2, 3, and 4 of E. coli had high affinities for R-95867. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Among the drugs tested, CS-834 showed the highest efficacy against experimental pneumonia in mice caused by penicillin-resistant S. pneumoniae.

Administration, Oral↗

[Is coronary spasmodicity unchangeable?: a study with acetylcholine or ergonovine in patients with ischemic heart disease].

Fluctuations of spasmodicity have been reported in affected vessels in patients with vasospastic angina, but the incidence of spasmodicity induced by pharmacologic agents on both vessels with spasm and vessels without induced spasm has not been investigated. Repeated spasm provocation tests by acetylcholine or ergonovine were performed at 13.1 +/- 9.9 month intervals (3-50 months) in 111 vessels of 50 patients with ischemic heart disease, consisting of 19 old myocardial infarction and 31 angina pectoris, who did not undergo angioplasty or have signs of advancing atherosclerosis. Spasm was defined as present when more than 90 percent stenosis was accompanied by the appearance of usual chest pain or significant electrocardiographic changes. Ninety-six vessels (86.5%), 65 without spasm and 31 with spasm, revealed coincident responses and the remaining 15 vessels contrary reacted. The coincidence rate of spasmodicity in patients at intervals of within 24 months (90.2%) was significantly higher (p < 0.05) than that at intervals of over 24 months apart (70.4%). The spasm coincidence rate was 67.3% in the vessels with provoked spasm by either the first or second tests. Only one (0.9%) out of the 111 vessels showed obvious progressive atherosclerosis during this study. The majority of vessels showed identical spasmodicity within 2 years. In conclusion, coronary spasmodicity might remain unchanged for at least 2 years despite medication with calcium channel blockers and isosorbide dinitrate.

Acetylcholine↗