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Biomedical subjects

M Kawana

Publications and source records attributed to M Kawana.

At least 37 records · Page 2Linked to original sources

Early inflammatory changes of the Haemophilus influenzae-induced experimental otitis media.

Haemophilus influenzae is one of the most frequent pathogens of acute otitis media. To determine the middle ear response during the early stage of acute inflammation, a small amount of H. influenzae was inoculated into the bullae of guinea pigs through the tympanic membrane. The bullae were harvested at 6, 12, 24, 36, and 48 hours after H. influenzae inoculation and washed with phosphate-buffered saline (PBS). The number of viable H. influenzae and inflammatory cells, the concentrations of myeloperoxidase (MPO) and lysozyme in the washing suspensions were measured, and compared with those in PBS-inoculated control ears. The number of viable H. influenzae increased very rapidly from 6 to 12 hours after inoculation and remained stationary up to 48 hours. The number of inflammatory cells and the MPO concentration were significantly higher in the H. influenzae-inoculated ears than in the control ears from 12 to 48 hours after inoculation. The lysozyme concentration was already significantly higher at 6 hours in the H. influenzae-inoculated ears; the lysozyme was released in the middle ear before the accumulation of inflammatory cells and degranulation of MPO from inflammatory cells. The results indicated that inflammatory reactions were present already at 6 hours after bacterial inoculation, and were rapidly accelerated during the subsequent hours. Consequently, acute middle ear inflammatory responses were seen immediately following inoculation of viable bacteria, and these responses originated in direct responses of middle ear mucosa, and oxidative and non-oxidative neutrophil metabolic products, which may cause tissue injury.

Acute Disease↗

Cooperative interaction of GATA-2 and AP1 regulates transcription of the endothelin-1 gene.

Endothelin-1 (ET-1) is a 21-amino-acid vasoactive peptide initially characterized as a product of endothelial cells. Reporter gene transfection experiments have indicated that a GATA site and an AP1 site are essential for ET-1 promoter function in endothelial cells, and GATA-2 appears to be the active GATA factor which regulates ET-1 expression. To look for interactions between AP1 and GATA-2, transactivation experiments were performed with expression vectors encoding c-Jun, c-Fos, and GATA-2. Cooperativity between the AP1 complex and GATA-2 was observed as a synergistic increase in transcriptional activity of the ET-1 reporter plasmid. In addition, AP1 was able to potentiate the action of GATA-2 on reporter constructs lacking a functional AP1 site. In a similar fashion, GATA-2 was able to potentiate the action of AP1 despite deletion of the GATA site. Experiments with GATA-1 and GATA-3 expression vectors provided evidence that this capacity to interact with AP1 may be a characteristic of all GATA family members. Biochemical evidence for AP1-GATA interaction was provided by immunoprecipitation experiments. A GATA-2-specific antiserum was shown to immunoprecipitate in vitro-synthesized Jun and Fos protein from reticulocyte lysate. Also, antisera directed against Jun and Fos were able to immunoprecipitate from nuclear extracts a GATA-binding protein, indicating the association of AP1 and GATA proteins in vivo.

Base Sequence↗

Long-term prognosis of medically treated patients with acute myocardial infarction and one-vessel coronary artery disease.

Long-term prognosis was studied in 156 patients with acute myocardial infarction (AMI) with 1-vessel coronary artery disease (CAD). During a mean follow-up period of 110 months, 19 patients (14%) had reinfarction, 15 (9.6%) died (including 7 deaths of cardiac origin) and 15 (9.6%) were hospitalized for worsening of angina. A coronary arteriogram was obtained twice in 54 patients. The coronary arteriogram revealed multivessel CAD in all cases with reinfarction (n = 14). Ten percent of the patients with multivessel disease experienced a reinfarction during the initial 3 years after the onset of the first AMI. The recurrence rate of AMI in patients with 1-vessel disease increased gradually from the third year after the onset of their first AMI, reaching 10% in 6.7 years. The recurrence of AMI at the same region as the original infarction was detected in only 1 patient. Six of 19 patients (32%) with recurrence of AMI died and 13 survived after the reinfarction. It was difficult to predict future progression from the outcome of the comparison between the first and second coronary arteriograms. Thus, in patients with uncomplicated AMI with 1-vessel CAD, the prognosis is relatively good and the frequency of reinfarction is very low with conservative treatment.

Adult↗

Neutrophil oxygen metabolite inhibition of cultured chinchilla middle ear epithelial cell growth.

Middle ear inflammation in acute bacterial otitis media is characterized by accumulation of neutrophils in middle ear effusion. Since neutrophils release products that may injure surrounding tissues, we studied the effect of neutrophil metabolic products on middle ear epithelial cells (MEECs) in vitro. Chinchilla MEECs were incubated with phorbol myristate acetate (PMA)-activated human neutrophils or with hydrogen peroxide (H2O2). Cell growth, which was measured by 3H-thymidine incorporation, was inhibited by activated neutrophils and by H2O2. Unstimulated neutrophils, PMA alone, and catalase alone did not affect the viability of MEECs. Catalase, an enzyme that reduces H2O2, partially blocked the inhibitory effect of activated neutrophils and completely blocked the inhibitory effect of H2O2. Inhibition of MEEC metabolism by neutrophil-reactive oxygen species may contribute to epithelial injury, which may prolong the middle ear inflammatory response and lead to chronic tissue damage.

Animals↗

Improvement of regional wall motion in medically treated myocardial infarction with single-vessel coronary artery disease.

Long-term changes in regional wall motion (RWM) following acute myocardial infarction (AMI) in 42 patients with uncomplicated single-vessel disease were examined retrospectively by repeat cardiac catheterizations. The first and second cardiac catheterizations were performed at an average of 28 days and 6.6 years after the onset of AMI, respectively. All 42 patients underwent first and second cardiac catheterizations without undergoing coronary artery bypass surgery or coronary angioplasty. Regional left ventricular functions were analyzed by the centerline method using a right anterior oblique left ventriculogram. The wall motion abnormality score (WMAS) was defined as [# chord below -2SD] x [mean SD chord below -2SD]. The improvement in the WMAS was more prominent in cases with an occluded infarct-related artery. Thus, we concluded that 1) RWM improves significantly with medical treatment in long-term follow-up in cases of uncomplicated AMI with single-vessel disease, and 2) the improvement of RWM is completed within the first few weeks after AMI in cases with a patent infarct-related artery.

Adult↗

Clinical usefulness of three-dimensional reconstruction of the temporal bone from CT scans in cholesteatoma cases.

The importance of computed tomography (CT) in analyzing temporal bone diseases has increased, and the ability to reconstruct the temporal bone structures in three dimensions from multiple CT films has been required. In order to facilitate the visualization of temporal bone structures, we tried reconstructing temporal bone CT images three-dimensionally using a personal computer, and evaluated the possibility of using three-dimensional CT images clinically. Temporal bone CT scan films from five cases of cholesteatoma and a case of otosclerosis as control were examined. Four temporal bone structures (temporal bone contour, middle ear, mastoid, and inner ear) and cholesteatoma, extracted from enlarged black and white CT films, were inputted to the personal computer. Data import and image reconstruction procedures were performed using commercially available software. Our results indicate that three-dimensional reconstructions contribute to visualizing temporal bone structures spatially, and to choosing surgical approaches in difficult cases, such as petrous bone cholesteatoma. In conclusion, three-dimensional reconstructions using a personal computer is useful in the diagnosis and treatment of cholesteatoma.

Adolescent↗

Penicillin treatment accelerates middle ear inflammation in experimental pneumococcal otitis media.

Most Streptococcus pneumoniae strains are killed by very low concentrations of penicillin and other beta-lactam antibiotics, yet middle ear inflammation and effusion persist for days to weeks after treatment in most cases of pneumococcal otitis media. To study the effect of beta-lactam antibiotic treatment on pneumococci and the middle ear inflammatory response during pneumococcal otitis media, we measured concentrations of pneumococci, inflammatory cells, and lysozyme in middle ear fluid (MEF) by using the chinchilla model. Procaine penicillin G given intramuscularly 12 and 36 h after inoculation of pneumococci into the middle ear caused a significant acceleration in the MEF inflammatory cell concentration compared with that in untreated controls, with a significant peak in the inflammatory cell concentration 24 h after pneumococcal inoculation. The lysozyme concentration in MEF also increased more rapidly in treated than in control animals. Viable pneumococci were not detected in MEF after the second dose of penicillin, but the total pneumococcal cell concentration remained unchanged for at least 45 days. Therefore, penicillin treatment accelerated middle ear inflammation while killing pneumococci, but treatment did not accelerate clearance of the nonviable pneumococcal cells from MEF. Further studies will need to define the contribution of these responses to acute and chronic tissue injury.

Animals↗

Role of the bacterial cell wall in middle ear inflammation caused by Streptococcus pneumoniae.

The pathogenesis of middle ear inflammation caused by Streptococcus pneumoniae was explored in the chinchilla model with different pneumococcal cell wall (CW) preparations, including isolated native CW, M1 muramidase CW (M1-CW) digest, amidase CW digest, and M1 peptidoglycan (M1-PG) digest. Inflammatory cell and lysozyme concentrations in middle ear fluid (MEF) were measured between 6 and 72 h after the middle ears were inoculated with one of the preparations or sterile saline. Middle ear histopathology was measured quantitatively at 72 h. Native CW, M1-CW digest, and amidase-CW digest caused significantly more inflammatory cell influx and lysozyme accumulation in MEF than saline did. M1-PG digest also caused more inflammatory cell influx and lysozyme accumulation in MEF than saline did but caused less inflammation than native CW or either CW digest. Epithelial metaplasia was significantly greater in ears inoculated with native CW than in ears inoculated with the CW or PG digest or with saline. Pneumococcal CW is, therefore, the principal factor that initiates middle ear inflammation in acute pneumococcal otitis media, and CW teichoication seems to be important in initiating this response.

Amidohydrolases↗

The synthesis of cyclopropano nucleosides.

A tricyclic, fused cyclopropano nucleoside 8 containing a ketal group was synthesized by the one-pot seven sequential reactions of a trimesylated allofuranosyl adenine derivative 6 with Mg(OMe)2. When KOH was used instead of Mg(OMe)2, an alpha, beta-unsaturated ketonucleoside 7 was obtained.

Adenosine↗

[Phase III trial of 99mTc-rhenium colloid for lymphoscintigraphy].

A multicenter study was carried out on 191 patients (196 examinations) with lymphatic system disorders to evaluate the efficacy and safety of 99mTc-rhenium Colloid, a tracer for lymphoscintigraphy (TCK-17). Local pain and swelling occurred at the site of injection in 79.6% and 5.1% of patients, respectively, and 2 patients experienced mild fever. The accuracy was calculated on the basis of the results obtained by other diagnostic methods. Lymphoscintigraphy using TCK-17 was sensitive diagnostic procedures, but low specificity. The efficacy was classified into five grades: "Excellent", "Good", "Moderate", "Equivocal", and "Poor". 67.3% of all examination were evaluated as "Excellent" or "Good". This study revealed TCK-17 was a useful radiopharmaceutical for lymphoscintigraphy because of its safety and effectiveness.

Adult↗

Atrial natriuretic peptide and brain natriuretic peptide coexist in the secretory granules of human cardiac myocytes.

To elucidate the intracellular localization of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human cardiac myocytes, an immunocytochemical study was carried out by a double immunogold technique using antisera highly specific for ANP and BNP. Surgical and autoptic tissue specimens of human heart were studied. In the atrial myocytes, ANP was localized in almost all of the secretory granules, whereas BNP was colocalized with ANP in some of the granules. Although very few secretory granules were observed in ventricular myocytes, colocalization of ANP and BNP was basically the same as in atrial myocytes. No immunoreactive products were found in the control studies. These results suggest that secretion of BNP is under a regulatory mechanism similar to that of ANP.

Atrial Natriuretic Factor↗

Plasma immunoreactive endothelin, but not thrombomodulin, is increased in patients with essential hypertension and ischemic heart disease.

To ascertain an involvement of vascular endothelial cells in cardiovascular disease, we have determined plasma levels of two endothelium-derived substances, endothelin (ET) and thrombomodulin (TM), in essential hypertension (EH) and ischemic heart disease. Plasma ET was determined by radioimmunoassay (RIA) after extraction. Plasma TM levels were determined by enzymunoimmunoassay. Plasma ET levels were significantly elevated in patients with EH involving target organ damage, vasospastic angina pectoris (VSA), and acute myocardial infarction (AMI), especially in those associated with cardiogenic shock. There was a weak but significant correlation between plasma ET levels and serum creatinine concentration in patients with EH. Plasma ET levels were elevated even before the coronary spasm in patients with VSA, whereas they did not show any further increase during the spasm. In contrast, plasma TM levels in patients with EH and VSA did not show a significant difference from that in normal subjects. These results suggest that ET plays an important role in the pathophysiology of EH and ischemic heart disease, and also that increases in plasma ET cannot be simply attributed to a leakage of the peptide from the injured endothelial cells.

Angina Pectoris↗

Oxidative metabolic products released from polymorphonuclear leukocytes in middle ear fluid during experimental pneumococcal otitis media.

To determine whether oxidative metabolic products of phagocytic cells are present in the middle ear during experimental pneumococcal otitis media, we measured the concentration of myeloperoxidase (MPO) in middle ear fluid (MEF) and the capacity of neutrophils isolated from MEF and peripheral blood to produce MPO and superoxide anion (O2-) after in vitro stimulation. Free MPO in MEF was significantly increased 24 and 48 h after either viable or nonviable pneumococci were inoculated into the middle ear. In vitro-stimulated production of MPO and O2- from middle ear neutrophils was significantly less than that from peripheral blood neutrophils 24 h after nonviable pneumococci were inoculated but similar to it after 48 h. Twenty-four hours after viable pneumococci were inoculated, middle ear neutrophils stimulated in vitro produced less MPO but the same amount of O2- as did blood neutrophils. Oxidative metabolic products, therefore, are released from phagocytic cells into the MEF during pneumococcal otitis media, and future studies will need to define the contribution of these products to acute and chronic middle ear tissue injury.

Animals↗