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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 361 records · Page 20Linked to original sources

Nerve growth factor induces resistance of PC12 cells to nitric oxide cytotoxicity.

Nitric oxide (NO) donors, sodium nitroprusside and NOC 7, caused pheochromocytoma (PC12) cell death in a concentration and time-dependent manner. This cytotoxicity was blocked by the NO trapping agent, oxyhemoglobin. A membrane permeable cGMP analogue had no cytotoxicity in a reasonable concentration. Moreover, the selective inhibitor of cGMP-dependent protein kinase, KT5823, had no effect on NOC 7 cytotoxicity. These results suggest that NO caused PC12 cell death but not through the cGMP pathway. Additionally, this NO-induced PC12 cell death is not accompanied by DNA fragmentation. Nerve growth factor (NGF), which is able to rescue PC12 cells from serum deprivation, failed to protect PC12 cells from NO-induced cell death by acute treatment. However, PC12 cells differentiated by NGF treatment for more than 3 days did not die after NO exposure. The differentiated PC12 cells, but not undifferentiated cells, expressed NO synthase (NOS). NGF-differentiated PC12 cells acquired the resistance to NO, by a mechanism not yet identified, accompanied by the expression of NOS.

Animals↗

Impairment of phagocytic cell respiratory burst by UVA in the presence of fluoroquinolones: an oxygen-dependent phototoxic damage to cell surface microvilli.

Fluoroquinolones are widely used clinically as broad-spectrum antimicrobial agents. One of their side effects is UVA-dependent photosensitivity, observed after the skin is exposed to sunlight. We have investigated five fluoroquinolones and have found that their phototoxicity is oxygen dependent. Human phagocytic leucocytes were stimulated with serum opsonized zymosan to produce superoxide radical (O2-) (respiratory burst) in the presence of a sensitive O2(-)-specific cypridina luciferin analogue, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazol (1,2-alpha) pyrazin-one hydrochloride (MCLA), as chemiluminescence reagent with which O2- can react to induce photon emission. The photon count was used as a measure of respiratory burst activity. When leucocytes were irradiated with UVA for 10 min in the presence of 3 micrograms ml-1 lomefloxacin, ciprofloxacin or norfloxacin, a marked decrease in respiratory burst activity was observed; in this respect, ofloxacin and tosufloxacin were weak. Scanning electron microscopy revealed that the cell surface microvilli were destroyed. The phototoxicity of fluoroquinolones could be abolished if oxygen in the tests was replaced by nitrogen or if the aminothiol DL-cysteine (1.5 mg ml-1) was added prior to irradiation. It is suggested that an oxygen species derived from UVA-excited drug molecules and oxygen mediates the phototoxicity of these fluoroquinolones.

Anti-Infective Agents↗

Effects of cigarette smoke on nitric oxide-induced increase in cyclic GMP in nerve terminals of rat cerebral cortex.

Since nitric oxide (NO) has been widely accepted as a novel neuromodulator, which activates soluble forms of guanylate cyclase to increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels, the effect of water-soluble substance in cigarette smoke on cyclic GMP levels were investigated using nerve terminals prepared from rat cerebral cortex. Although the smoke-substance itself failed to affect cyclic GMP levels in the synaptosomes, the smoke-substance significantly inhibited the increases in cyclic GMP levels induced by NO donors. The blocking effect of the smoke-substance was inhibited by concomitant incubation with superoxide dismutase, but not with mannitol. In addition, the effect of smoke-substance was mimicked by products of the xanthine/xanthine oxidase system, but not by nicotine. The effect of smoke-substance was preserved at least 7 days after they were stored at room temperature. Therefore, these results suggest that the smoke-substance may possess long half-lives to produce the radicals which inactivate NO, and to inhibit the increase in cyclic GMP levels in nerve terminals. The interference with NO may explain the part of mechanism in effects of cigarette smoke on neuronal functions.

Analysis of Variance↗

Changes in levels of mRNAs of transforming growth factor (TGF)-beta1, -beta2, -beta3, TGF-beta type II receptor and sulfated glycoprotein-2 during apoptosis of mouse uterine epithelium.

To examine the roles played by transforming growth factors (TGF)-beta1, -beta2, -beta3, and TGF-beta type II receptors in the induction of apoptosis in the mouse uterine epithelium after estrogen deprivation, we investigated the expression of their mRNAs and the mRNA of sulfated glycoprotein-2 (SGP-2). Pellets containing 100 microg estradiol-17beta (E2) were implanted into ovariectomized mice and removed four days later. Apoptotic indices (percentage of apoptotic cells) of both luminal and glandular epithelia increased after E2 pellets were removed, but administration of progesterone (P), 5alpha-dihydrotestosterone (DHT), or continued implantation of E2 pellets suppressed this increase. Levels of mRNAs of TGF-beta1, -beta2, and -beta3, and SGP-2 did not increase after estrogen deprivation. However, estrogen deprivation caused a gradual increase in the level of TGF-beta type II receptor mRNA, and its level increased about six-fold six days later. Moreover, E2, P, and DHT markedly decreased the level of TGF-beta type II receptor mRNA. In situ hybridization demonstrated that mRNAs of TGF-beta1, -beta2, -beta3 and TGF-beta type II receptor were localized to the epithelium. Exogenous administration of TGF-beta1 into the uterine stroma induced apoptosis in the epithelium, a finding that suggests that signals produced by TGF-betas can induce apoptosis. Therefore, the present results suggest that increased sensitivity of uterine epithelial cells to TGF-betas, as demonstrated by an increase in TGF-beta type II receptor mRNA, is involved in the induction of apoptosis after estrogen deprivation, although signals produced by TGF-betas do not appear sufficient to induce apoptosis.

Animals↗

D-mannose dimer introduced human recombinant interleukin- 1 alpha, NEO IL-1 alpha, exhibits altered tissue distribution in mice.

Previous studies have demonstrated that the carbohydrate-introduced recombinant human IL-l alpha exhibited impairment in both biologic activities in all the experiments in vitro and receptor binding capacity compared with intact IL-l alpha. However, the glycosylated IL-l alpha exhibited selective activities in vivo. In this study, we compared the tissue distribution of IL-l alpha and IL-l alpha coupled with D-Mana (l-6)Man [Man2 alpha) (l-6)IL-l alpha] in mice. Mice were injected by intravenous and intraperitoneal routes with 2.0 mu g radiolabeled IL-l alpha. At 1 and 2 h after IP injection, the level of Man2 alpha) (l-6)IL-l alpha decreased twofold compared with that of IL-l alpha in kidney. In contrast, at 1 hour after administration, Man2 alpha) (l-6)IL-l alpha exhibited higher levels than IL-l alpha in blood, heart, and liver. No significant difference was observed in brain at each time point. IV injection demonstrated that Man2 alpha)(l-6)IL-l alpha decreased to approximately one-half the level of rhIL-l alpha in kidney. In contrast, Man(2 alpha) (l-6)IL-l alpha increased twofold over that of IL-l alpha in liver at 1 h after dosing. These findings are consistent with the result of IP injection. There was no significant difference between IL-l alpha and glycosylated IL-l alpha at 4 h after IV administration. These differences in tissue distribution may contribute to the selective activities of glycosylated IL-l alpha in vivo. The results also suggest that by coupling with mannose dimer, it is possible to develop neocytokines prone to liver distribution.

Animals↗

Temporal and spatial distribution of ferredoxin isoproteins in tomato fruit.

Five ferredoxin (Fd) isoproteins (FdA, FdB, FdC, FdD, and FdE) were isolated from tomato (Lycopersicon esculentum cv Momotaro) fruit. These isoproteins showed differential temporal and spatial accumulation patterns. FdA and FdC were present in leaves. FdE was present in roots, and FdB and FdD were fruit-specific. During fruit growth, the relative abundance of FdA decreased and that of FdE increased. The FdE/FdA ratio was higher in the inner tissues of the fruit than in the outer tissue, and it was correlated with starch accumulation. In darkgrown fruit the contents of FdA, FdB, and FdC, as well as chlorophyll, decreased remarkably relative to their light-grown counterparts; however, the contents of FdE and starch did not change significantly. Under in vitro conditions FdE showed higher cytochrome c reduction activity than FdA and FdB. These results, together with their N-terminal sequences, indicate that both photosynthetic- and heterotrophic-type Fd isoproteins are present in tomato fruit.

Amino Acid Sequence↗

A new murine lymphocytotoxic monoclonal antibody recognizing HLA-A2, -A28 and -A9.

Monoclonal antibodies recognizing polymorphic as well as monomorphic epitopes on HLA antigens are important tools for understanding the immunobiology of HLA molecules. We immunized BALB/c mice with a HLA-A2 transfectant and screened for hybridomas which reacted with a HLA-A2 transfectant but not with a HLA-B75 transfectant. After subcloning by limiting dilution four times, a hybridoma secreting a monoclonal antibody (mAb) (IgG 2a, kappa) designated 1-145 was established. 1-145 reacted with Epstein-Barr virus transformed B lymphoblastoid cell lines (B cell lines) which expressed HLA-A2, -A28, -A23 and -A24. The titer of 1-145 in culture supernatant against HLA-A2 and -A28 antigens was similar and the titer against HLA-A23 was lower. 1-145 reacted with cells expressing HLA-A24 but the titer against HLA-A24 antigens was even lower than that against HLA-A23 antigens. The HLA-A24 antigens on the peripheral blood lymphocytes were not detected by 1-145 possibly due to the lower expression compared to the B cell lines. These differences of the titers were reflected to microlymphocytotoxicity assay in which 1-145 culture supernatant lysed all PBLs expressing HLA-A2,-A28 and -A23 but did not lyse PBLs expressing HLA-A24. Published deduced amino acid sequence data of HLA class 1 molecules indicate that Lys in position 127 may be critical for 1-145 binding.

Amino Acid Sequence↗

Altered prostaglandin metabolism induced by angiotensin-converting enzyme inhibitors in broncho-alveolar lavage fluid of the guinea pig.

The aim of this study was to investigate if prostaglandin (PG) metabolism is altered by angiotensin-converting enzyme (ACE) inhibitors as determined in the broncho-alveolar lavage fluid (BALF) of the guinea pig. Enalapril or imidapril was orally administered once a day for 2 weeks to Hartley male guinea pigs. Twenty-four hours after the last treatment, BALF was collected and the concentrations of PGI2, thromboxane A2 (TXA2) and PGE2 were measured by enzyme immunoassay. Enalapril significanlty P < 0.05) increased the TXA2 content, which was inhibited by indomethacin treatment and significantly (P < 0.05) decreased the PGI2 content. Imidapril, however, did not affect TXA2 or PGI2 generation. These findings suggest that altered PG metabolism may be associated with coughing as a side effect of enalapril.

Analysis of Variance↗

Induction therapy with all-trans retinoic acid for acute promyelocytic leukemia: a clinical study of 10 cases, including a fatal [correction of fetal] case with thromboembolism.

Ten patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Eight of 10 patients achieved complete remission (CR), and among the 8 newly diagnosed cases, 7 achieved CR. Five of 8 CR cases remained in CR after 8 to 30 months. Except for hypotension and a large gastric ulcer resulting from hyperhistaminemia, the adverse effects of ATRA were generally mild. Severe thrombotic tendency occurred in a patient treated with ATRA combined with tranexamic acid. Intensive chemotherapy consisting of daunorubicin (DNR) and other agents was scheduled for the patients who achieved CR with ATRA.

Adult↗

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1993)].

Bacteria isolated from respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981, and the Ikemotor et al. have been investigating susceptibilities of the isolates of various antibacterial agents and antibiotics, and the relationships between the isolates and backgrounds of the patients and so forth each year. We discuss the results in detail. In 20 institutions around the entire Japan from October 1993 to September 1994, 584 strains of bacteria were isolated mainly from sputa of 473 patients with respiratory tract infections and presumed to be the etiological agents. MICs of various antibacterial agents and antibiotics were determined against 91 strains of Staphylococcus aureus, 98 strains of Streptococcus pneumoniae, 122 strains of Haemophilus influenzae, 91 strains of Pseudomonas aeruginosa (non-mucoid), 34 strains of Pseudomonas aeruginosa (mucoid), 42 strains of Moraxella subgenus Branhamella catarrhalis, 25 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were measured except the strains which died during transportation. 1. S. aureus S. aureus strain sfor which MICs of methicillin was higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 56.0%, but this frequency of the drug resistant bacteria was lower than the previous year's 61.4%. Arbekacin and vancomycin showed the highest activities against MRSA and MIC80s were 1 microgram/ml. 2. S. pneumoniae Benzylpenicillin among the penicillins showed potent activities against S. pneumoniae. Cefuzonam, cefotaxime and cefmenoxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; carbapenems, showed the most potent activity, and MIC90 was 0.063 microgram/ml. 3. H. influenzae All the drugs tested were quite active against H. influenzae. Cefotaxime, cefmenoxime, cefuzonam and cefixime among the cephems showed the most potent activities, and MIC90 were 0.063 microgram/ml against H. influenzae. Ofloxacin also showed MIC90 of 0.063 microgram/ml. 4. P. aeruginosa (mucoid) Tobramycin showed the most potent activity against P. aeruginosa (mucoid), and MIC80 was 1 microgram/ml. Ceftazidime, cefsulodin, imipenem, aztreonam, gentamicin and ciprofloxacin showed potent activities with MIC80s of 2 micrograms/ml. 5. P. aeruginosa (non-mucoid) Tobramycin showed the highest activity against P. aeruginosa (non-mucoid), and MIC80 was 1 microgram/ml, followed by ciprofloxacin with MIC80 of 2 micrograms/ml. Comparing to activities against P. aeruginosa (mucoid), all the drugs tested had relatively low activities against P. aeruginosa (non-mucoid). 6. K. pneumoniae. The activities of all drugs except ampicillin and minocycline were high against K. pneumoniae. Cefozopran, imipenem and carumonam showed the highest activities and MIC80s were 0.125 microgram/ml. Flomoxef showed the next highest activities with an MIC80 of 0.25 microgram/ml. 7. M.(B.) catarrhalis Imipenem showed the most potent activity against M.(B.) catarrhalis, with an MIC80 of 0.063 microgram/ml, followed minocycline and ofloxacin with their MIC80s of 0.125 microgram/ml. We also investigated year to year changes in the background of patients, as well as types of respiratory infectious diseases, and the etiological agents. As for patients background, there were many infectious diseases found among patients a high age bracket, and the patients over age 60 accounted for 61.3% of the diseases. The distribution by respiratory tract infections was as follows: chronic bronchitis and bacterial pneumonia accounted for the greatest numbers of cases with 31.1% and 26.0%, respectively, followed by bronchiectasis with 10.4%. In this year chronic bronchitis under age 29 were 41.7%, thus was much higher than 12.5% in previous year. This marked change was first noted in your research during the recent 5 years. As for frequencies of etiologic bacteria by respiratory tract infections, S. pneumoniae (ABSTRACT TRUNCATED)

Aged↗

[The antigen (CANDTEC antigen) detected by CAND TEC test for diagnosis of candidiasis].

Most guinea pigs inoculated with 5.4 x 10(9) of C. albicans intraperitoneally, produce CANDTEC antigen (GPCANDTECAG) in sera. The antigen is heat-labile (at 56 degrees C for 30 min) as is that in humans. According to gel filtration, the molecule size of the antigen from guinea pigs was 4000KDa or more. ELISA revealed the antigen-positive gel fractions to contain a small amount of mannan from the yeasts and C3. ELISA using rabbit anti-GPCANDTECAG serum indicated that the two CANDTEC antigens from guinea pigs and humans shared determinants. Gel filtration indicated that the CANDTEC antigen from patients was from 4000KDa to 3000KDa. In the antigen-positive gel fractions, IgM was detected by ELISA, but mannan and C3 were not detected. However, immunoblotting analysis on the antigen-positive fraction revealed a unique band of 200KDa, stained with concanavalin A-ALP. These findings indicate that CANDTEC antigens in guinea pigs and humans are immune complexes formed after infection of Candida, although the antigens have different components.

Animals↗

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1994)].

Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981. IKEMOTO et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 23 institutions around the entire Japan, 492 strains of presumably etiological bacteria were isolated mainly from the sputum of 421 patients with lower respiratory tract infections from October 1994 to September 1995. MICs of various antibacterial agents and antibiotics were determined against 70 strains of Staphylococcus aureus, 101 strains of Streptococcus pneumoniae, 92 strains of Haemophilus influenzae, 61 strains of Pseudomonas aeruginosa (non-mucoid strains), 25 strains of Pseudomonas aeruginosa (mucoid strains), 48 strains of Moraxella subgenus Branhamella catarrhalis, 14 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1. S. aureus. S. aureus strains for which MICs of oxacillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 51.4%, but the frequency of the drug resistant bacteria decreased comparing to the previous year's 56.0%. Vancomycin showed the highest activity against S. aureus with MIC80 of 0.5 microgram/ml. 2. S. pneumoniae. Most of the drugs tested showed potent activities against S. pneumoniae. Imipenem of carbapenems showed the most potent activity with MIC80 was 0.063 microgram/ml. Erythromycin and clindamycin showed low activities with MIC80s > or = 256 micrograms/ml. Among these strains, however, 46.5% and 68.3% of strains, were quite sensitive toward these agents, respectively, with MICs of 0.063 microgram/ml. 3. H. influenzae. The activities of all drugs were potent against H. influenzae tested. Cefmenoxime a cephem, showed the most potent activity, the MICs of this drug against all of the 92 strains were 0.063 microgram/ml. Ofloxacin also showed a potent activity, and inhibited about 96% of strains with MIC of 0.063 microgram/ml. 4. P. aeruginosa (mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 0.5 microgram/ml. Gentamicin, arbekacin and ciprofloxacin showed next potent activities, and their MIC80s were 2 micrograms/ml. 5. P. aeruginosa (non-mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (non-mucoid strains) with MIC80 of 2 micrograms/ml. Comparing to the activities against P. aeruginosa (mucoid strains), the activities of all the drugs tested were lower against P. aeruginosa (non-mucoid strains). 6. K. pneumoniae. Carumonam showed the most potent activity against K. pneumoniae with MIC80 of 0.063 microgram/ml. Cefozopran showed the next most potent activity with MIC80 of 0.125 microgram/ml. Ampicillin and cephems except cefpodoxime, cefozopran and cefditoren showed low activities and their MIC80s were > or = 16 micrograms/ml, and their MICs were all higher than > or = 4 micrograms/ml. 7. M. (B.) catarrhalis. Imipenem and ofloxacin showed the most potent activities against M. (B.) catarrhalis, their MIC80s were 0.063 microgram/ml. Erythromycin and minocycline showed the next highest activities with their MIC80s at 0.25 microgram/ml. Also, we investigated year to year changes in the background of patients, the respiratory infectious diseases, and the etiology of bacteria. Patients characteristics, in this period of investigation showed varieties of infectious diseases found in patients in a high age bracket, and the patients over age 60 accounted for 62.0% of all the cases. Different lower respiratory tract infectious were distributed as follows: chronic bronchitis and bacterial pneumonia accounted for the greatest number of cases with 35.6%, 27.1%, respectively, followed by

Adult↗

[Infections mononucleosis with pleural effusion].

A 24-year-old man was admitted to our hospital for further examination of pleural effusion. On physical examination, he had a temperature of 39 degrees C, the pharynx was painful and liver and spleen were enlarged. The leukocyte count was 5,700/microliters (atypical lymphocyte 6%). The serum LDH, GOT, GPT, ALP and gamma-GTP levels were elevated, and antibodies to Epstein-Barr viral capsid, early, and nuclear antigens were diagnostic of a primary Epstein-Barr virus infection. The CD4/CD8 ratio of peripheral blood lymphocyte was decreased to 0.2. The pleural effusion was exudate, and infiltration of mononuclear cells was noted. The CD4/CD8 ratio of lymphocytes in the effusion also was decreased to 1.1. The result of pleural biopsy showed a perivascular infiltration of mononuclear cells and immunological stain showed that the infiltrated cells were dominantly T-lymphocytes (about 90%). These findings suggested that the pathogenesis of pleural effusion in infectious mononucleosis was a pleulitis due to the infiltration of T-lymphocytes. Pleural effusion is known as a rare complication of infectious mononucleosis.

Adult↗

Effects of the novel water-soluble calcium antagonist (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride on the endothelium-independent and endothelium-dependent contraction in isolated canine cerebral arteries.

The inhibitory effects of NKY-722 (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride, CAS 117241-46-0) on endothelium-independent and endothelium-dependent contractions were examined in comparison with nicardipine in isolated canine cerebral arteries. NKY-722 relaxed the cerebral arteries contracted endothelium-independently by KCl, prostaglandin F2 alpha U-46619 (a thromboxane A2 agonist) and endothelin-1 with IC50 = 2.5, 3.4, 2.8 and 3.6 x 10(-10) mol/l, respectively. On the basis of IC50 values, NKY-722 was about 2 times more effective than nicardipine. Pretreatment of NKY-722 and nicardipine inhibited the endothelium-independent contraction induced by KCl and serotonin to a similar degree. NKY-722 attenuated the endothelium-dependent contractions caused by acetylcholine (ACh), adenosine diphosphate and KO2 with IC50 = 1.7, 3.8 and 1.4 x 10(-9) mol/l, respectively. NKY-722 was about 2 times less effective than nicardipine. NKY-722 and nicardipine inhibited dose-dependently the endothelium-dependent contractions induced by hemolysate. NKY-722 was nearly equipotent to nicardipine on the phasic contraction and slightly more potent on the tonic contraction. The inhibitory effect of NKY-722 on the endothelium-independent contraction induced by KCl and the endothelium-dependent contraction induced by ACh were sustained for a longer time than that of nicardipine after repetitive wash-out. In conclusion, NKY-722 inhibited effectively the endothelium-independent and endothelium-dependent contractions in the cerebral arteries. The effect of NKY-722 was similar to, but longer-lasting than that of nicardipine.

Acetylcholine↗

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1992)].

Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan since 1981, and Ikemoto et al. have been investigating susceptibilities of the isolates to various antibacterial agents and antibiotics, and the relationships between the isolates and characteristics of the patients and so forth each year. We discuss the results in detail. In 20 institutions around the entire Japan from October 1992 to September 1993, 690 strains of bacteria were isolated mainly from sputa of 549 patients with lower respiratory tract infections and presumed to be the etiological bacteria. MICs of various antibacterial agents and antibiotics were determined against 101 strains of Staphylococcus aureus, 121 strains of Streptococcus pneumoniae, 122 strains of Haemophilus influenzae, 92 strains of Pseudomonas aeruginosa (non-mucoid), 32 strains of Pseudomonas aeruginosa (mucoid), 52 strains of Moraxella subgenus Branhamella catarrhalis, 28 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were measured except the strains which died during transportation. 1. S. aureus S. aureus strains for which MICs of methicillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 61.4% and the frequency of the drug resistant bacteria was higher than the previous year's 58.3%. MICs values indicated that arbekacin was as active as vancomycin against all the strains on S. aureus. 2. S. pneumoniae Benzylpenicillin among the penicillins showed potent activities against S. pneumoniae. Cefuzonam, cefazolin, cefotaxime and cefmenoxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; carbapenems, showed the most potent activity, and MIC80 was 0.015 microgram/ml. 3. H. influenzae All the drugs tested were potent against H. influenzae. Ampicillin among the penicillins showed MIC80 1 microgram/ml against H. influenzae. Cefotaxime, cefmenoxime, cefuzonam and cefixime showed the most potent activities, and MIC80s were 0.063 microgram/ml. The antimicrobial activity of ofloxacin was equivalent to those of cephems. 4. P. aeruginosa (mucoid) Ciprofloxacin showed the most potent activity against P. aeruginosa (mucoid), and MIC80 was 1 microgram/ml. Cefsulodin, aztreonam, carumonam and tobramycin showed the next most potent activities with an MIC80s of 2 micrograms/ml. 5. P. aeruginosa (non-mucoid) Tobramycin and ciprofloxacin showed the highest activities against P. aeruginosa (non-mucoid) with an MIC80s of 2 micrograms/ml. Norfloxacin also showed some activity, and MIC80 was 4 micrograms/ml. Comparing to activities against P. aeruginosa (mucoid), all the drugs tested showed lower activities against P. aeruginosa (non-mucoid). 6. K. pneumoniae The activities of all drugs except penicillins were high activities against K. pneumoniae. Carumonam showed the most potent activity with an MIC80 of 0.063 microgram/ml, followed by flomoxef, cefixime and cefozopran with their MIC80s of 0.125 microgram/ml. 7. M.(B.) catarrhalis Imipenem; carbapenems, showed the most potent activity against M.(B.) catarrhalis with an MIC80 0.063 microgram/ml. Minocycline and ofloxacin showed MIC80s 0.125 microgram/ml, respectively. We also investigated year to year changes in the background of patients, as well as types of respiratory infectious diseases, and the etiological bacteria. As for patients backgrounds, there were many infectious diseases found among patients in a high age bracket, and the patients over age 60 accounted for 60.8% of the diseases. The distribution by lower respiratory tract infections was as follows: bacterial pneumonia and chronic bronchitis accounted for the greatest numbers of cases with 30.4%, 29.5%, respectively, followed by bronchiectasis with 12.2%. As for frequencies of etiologic bacteria for respiratory tract infections, H. influenzae: 22.2%, and S. pneumoniae: 15.1% in chronic bronchitis; S. pneumoniae: 2

Anti-Bacterial Agents↗

[Recovery from descending necrotizing mediastinitis and multiple organic failure after seven months of mechanical ventilation].

A 61-year-old man with a history of hypertension and diabetes mellitus had a tooth extracted. Nine days later, he was admitted to the hospital with complaints of high fever, dyspnea, and anterior chest pain. Physical examination revealed a drowsy man with a fever of 38.2 degrees C, blood pressure of 66/44 mmHg, and marked redness and swelling from the neck to anterior part of the chest. Laboratory examination indicated severe infection and multiple organ failure, consisting of cardiac, respiratory, renal, and hepatic failure, with disseminated intravascular coagulation. Chest X-ray and CT-scan films showed abscesses extending from the neck to the mediastinum, and bilateral pleural effusion. Immediately, he was treated with catecholamines, furosemide, mechanical ventilation with a high concentration of oxygen, continuous drainage, repeated skin incisions, and broad-spectrum antibiotics. In addition, steroid pulse therapy was administered for persistent respiratory failure. On the 28th hospital day, a fistula developed between the trachea and the mediastinum, and an intratracheal tube had to be inserted through the fistula. On the 212 th hospital day, after intravenous hyperalimentation, continuous intravenous insulin infusion, and administration of broad-spectrum antibiotics, catecholamines, and furosemide, the patient was weaned from mechanical ventilation. A restrictive ventilatory defect due to ankylosis and atrophy of underused muscles was noted after weaning, but the PaO2 was high with a low dose of oxygen (1 to 2 l/min), and 21 months later, the blood gases were normal while the patient was breathing room air. As of January, 1996, he was undergoing rehabilitation to promote his recovery from ankylosis, muscle atrophy, and speech dysfunction.

Catecholamines↗

Effects of 1-[3-(4-benzhydryl-1-piperazinyl)propyl]-3- (1H-imidazol-1-ylmethyl)-1H-indole-6-carboxylic acid with thromboxane A2 synthetase inhibitory and H1-blocking activities on anaphylactic bronchospasm.

1-[3-(4-Benzhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl )- 1H-indole-6-carboxylic acid (CAS 172544-75-1, KY-234) was characterized pharmacologically. KY-234 (10(-9)-10(-6) mol/l) and ozagrel (10(-8)-10(-5) mol/l) inhibited the production of thromboxane A2 (TXA2) in rabbit platelets. KY-234 and pyrilamine at concentrations of 10(-9)-10(-6) mol/l relaxed the isolated guinea pig trachea contracted with histamine, while neither drug attenuated the heart rate increased by histamine. Cimetidine antagonized histamine in the right atrium but not in the trachea. KY-234 (10(-8)-10(-5) mol/l) and ozagrel (10(-7)-10(-4) mol/l), but not pyrilamine, attenuated the contraction induced by leukotriene D4 (LTD4) and platelet-activating factor in the lung parenchymal strips. In anesthetized guinea pigs, KY-234 (1-10 mg/kg p.o.) inhibited the LTD4- and histamine-induced bronchoconstriction. Ozagrel and terfenadine inhibited only the LTD4- and histamine-induced constrictions. KY-234 (3-30 mg/kg p.o.) inhibited the anaphylactic bronchoconstriction continuously for 15 min after antigen-challenge. Terfenadine (3-30 mg/kg p.o.) inhibited the constriction more strongly within the first 5 min (fast phase) than it did within 5 to 15 min (slow phase) after the challenge. Ozagrel (100 mg/kg p.o.) slightly attenuated only the constriction during the slow phase. These findings demonstrated that KY-234 has a selective TXA2 synthetase-inhibitory and H1-blocking activity and protects against anaphylactic bronchospasm more effectively than a TXA2 synthetase inhibitor or H1-blocker alone.

Anaphylaxis↗

[A case of bilateral infarction of medial pontomedullary junction].

A 69-year-old man suffered from dizziness and nausea after work, and was admitted to our hospital on the next day. On admission, he showed bilateral horizontal nystagmus and left hemiparesis. On the 3rd day he vomited frequently, and the dizziness became worse. Bilateral horizontal and upward gaze palsy and bilateral facial nerve palsy were observed. Brain MRI on the 5th day disclosed bilateral upper medial medullary infarction that extended to the pontomedullary junction. Cerebral angiography on the 13th day revealed occlusion of the right vertebral artery. This case did not show typical medial medullary syndrome. The mechanism was unknown, but similar cases were reported. Recently, many cases of medullary infarction are reported with the progress of MRI technology. It is suggested that the addition of the new concepts on the conventional syndromes of medullary infarction is necessary.

Aged↗