Biomedical subjects

N Kitamura

Publications and source records attributed to N Kitamura.

At least 19 recordsLinked to original sources

PubMed1997

Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor.

Hepatocyte growth factor (HGF) activator is a serine protease responsible for proteolytic activation of HGF in response to tissue injury and thus plays an important role in the regulation of biological functions of HGF in regenerating tissue. We previously purified an inhibitor of HGF activator (HGF activator inhibitor type 1, HAI-1) from the conditioned medium of a human stomach carcinoma cell line MKN45 and cloned its cDNA. HAI-1 is a novel member of the Kunitz family of serine protease inhibitors. In the present study, we purified a second type of HGF activator inhibitor (HAI-2) from the conditioned medium of MKN45 cells and molecularly cloned its cDNA. The cDNA sequence revealed that HAI-2 is derived from a precursor protein of 252 amino acids and contains two Kunitz domains, indicating that HAI-2 is also a member of the Kunitz family of serine protease inhibitors. The primary translation product of HAI-2 has a hydrophobic sequence in the COOH-terminal region, suggesting that, like HAI-1, HAI-2 is produced in a membrane-associated form and secreted in a proteolytically truncated form. Because HAI-2 and HAI-1 are potent inhibitors specific for HGF activator, they may be involved in regulation of proteolytic activation of HGF in injured tissues.

Amino Acid Sequence↗

PubMed1997

Hrs, a tyrosine kinase substrate with a conserved double zinc finger domain, is localized to the cytoplasmic surface of early endosomes.

Hrs is a 115-kDa double zinc finger protein that is rapidly tyrosine phosphorylated in growth factor-stimulated cells. However, its function remains unknown. Here we show that Hrs is localized to early endosomes. Intracellular localization of endogenous Hrs and exogenously expressed Hrs tagged with the hemagglutinin epitope was examined by immunofluorescence staining using anti-Hrs and anti-hemagglutinin epitope antibodies, respectively. Hrs was detected in vesicular structures and was colocalized with the transferrin receptor, a marker for early endosomes, but only partially with CD63, a marker for late endosomes. A zinc finger domain deletion mutant of Hrs was also colocalized with the transferrin receptor, suggesting that the zinc finger domain is not required for its correct localization. Immunoelectron microscopy showed that Hrs was localized to the cytoplasmic surface of these structures. By subcellular fractionation, Hrs was recovered both in the cytoplasmic and membrane fractions. The membrane-associated Hrs was extracted from the membrane by alkali treatment, suggesting that it is peripherally associated with early endosomes. These results, together with our finding that Hrs is homologous to Vps27p, a protein essential for protein traffic through a prevacuolar compartment in yeast, suggest that Hrs is involved in vesicular transport through early endosomes.

Amino Acid Sequence↗

PubMed1997

Measurement of intracellular Na+ concentration by a Na+-sensitive fluorescent dye, sodium-binding benzofuran isophthalate, in porcine adrenal chromaffin cells--usage of palytoxin as a Na+ ionophore.

Palytoxin was found to equilibrate sodium ions (Na+) across the cell membrane much faster than dose gramicidin, which has been frequently used to calibrate the intracellular Na+ concentration ([Na+]in), in cells treated with a Na+-sensitive fluorescent dye, sodium-binding benzofuran isophthalate (SBFI). Palytoxin was capable of equilibrating Na+ in cells treated with SBFI-acetoxymethyl ester (SBFI-AM) and in voltage-clamped cells loaded with SBFI through a patch pipette. Nicotine caused a dose-dependent increase in ([Na+]in) in porcine adrenal chromaffin cells treated with SBFI-AM and caused a simultaneous increase in [Na+]in and inward current in the voltage-clamped cells loaded with SBFI. Palytoxin has an advantage of calibrating ([Na+]in) in a shorter time than dose gramicidin because of its powerful ionophoretic activity.

Acrylamides↗

PubMed1997

P-selectin expression in a metastatic pancreatic tumor cell line (SUIT-2).

The human pancreatic tumor cell line SUIT-2 was derived from a metastatic lesion in the liver of a patient with pancreatic adenocarcinoma. SUIT-2 and clonal cell lines derived from it show spontaneous metastasis to lung and regional lymph nodes from s.c. nude mouse xenografts and were found to express P-selectin mRNA and protein. Surface expression of P-selectin protein was increased by exposure of the pancreatic tumor cells to thrombin, oxygen radicals, and trypsin, suggesting that common cellular mechanisms for regulating P-selectin surface expression exist among platelets, endothelial cells, and these pancreatic tumor cells. The finding that P-selectin is expressed by metastatic pancreatic tumor cells demonstrates that the range of cell types that express these adhesion molecules is broader than believed previously.

Adenocarcinoma↗

PubMed1997

Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor.

Hepatocyte growth factor (HGF) activator is a serine protease that is produced and secreted by the liver and circulates in the blood as an inactive zymogen. In response to tissue injury, the HGF activator zymogen is converted to the active form by limited proteolysis. The activated HGF activator converts an inactive single chain precursor of HGF to a biologically active heterodimer in injured tissue. The activated HGF may be involved in the regeneration of the injured tissue. In this study, we purified an inhibitor of HGF activator from the conditioned medium of a human MKN45 stomach carcinoma cell line and molecularly cloned its cDNA. The sequence of the cDNA revealed that the inhibitor has two well defined Kunitz domains, suggesting that the inhibitor is a member of the Kunitz family of serine protease inhibitors. The sequence also showed that the primary translation product of the inhibitor has a hydrophobic sequence at the COOH-terminal region. Inhibitory activity toward HGF activator was detected in the membrane fraction as well as in the conditioned medium of MKN45 cells. These results suggest that the inhibitor may be produced as a membrane-associated form and secreted by the producing cells as a proteolytically truncated form.

Amino Acid Sequence↗

PubMed1997

Calcium channel subtypes in porcine adrenal chromaffin cells.

The effects of nifedipine, omega-conotoxin GVIA (omega-CgTx) and omega-agatoxin IVA (omega-AgTx) on Ca2+ currents, a 60-mM-K+-induced increase in intracellular Ca2+ concentration (-Ca2+-i) and catecholamine secretion were examined to clarify the subtypes of Ca2+ channels in cultured adrenal chromaffin cells from the pig. Nifedipine, omega-CgTx, and omega-AgTx inhibited Ca2+ currents in a dose-dependent manner, suggesting the presence of L-, N- and P-type Ca2+ channels. The maximal doses of nifedipine (10 microM), omega-CgTx (1 microM), and omega-AgTx (0.1 microM) inhibited Ca2+ currents to 85%, 22%, and 94% of control currents, respectively. The inhibitory effects of these three blockers were observed in the same cell, indicating that at least three subtypes of Ca2+ channels are present in porcine chromaffin cells. The increase in -Ca2+-i and catecholamine secretion induced by 60 mM K+ were inhibited equally by nifedipine (10 microM) and omega-CgTx (1 microM), but not by omega-AgTx (0.1 microM). These results suggest that L-, N- and P-type Ca2+ channels are present in porcine adrenal chromaffin cells, and that the major pathways of Ca2+ entry evoked by a high concentration of K+ are L- and N-type Ca2+ channels.

Adrenal Glands↗

PubMed1997

Stimulation of liver regeneration and function after partial hepatectomy in cirrhotic rats by continuous infusion of recombinant human hepatocyte growth factor.

BACKGROUND/AIMS: Radical resection is accepted as one of the most curative treatments for hepatocellular carcinoma. However, most patients have coexisting cirrhosis and their liver function is usually impaired. It is therefore important to stimulate the regeneration and function of the remnant cirrhotic liver after hepatectomy. Hepatocyte growth factor is a potent mitogen that has been suggested to play a crucial role in liver regeneration. METHODS: In this study, we performed 45% hepatectomy in rats with cirrhosis induced by thioacetamide, and administered recombinant human hepatocyte growth factor (rhHGF) with dextran sulfate by continuous infusion into the jugular vein with an infusion pump. RESULTS: rhHGF stimulated an increase in the wet weight of the remnant liver compared with untreated control rats. The proliferating cell nuclear antigen labeling index showed that this increase resulted from the stimulation of DNA synthesis. Serum levels of liver enzymes increased after hepatectomy, but returned to the prehepatectomy level more rapidly in rhHGF-treated rats than in controls. rhHGF increased hepatic protein synthesis above prehepatectomy levels and also markedly increased the serum levels of hepatic lipid metabolites. CONCLUSIONS: These results demonstrate that continuous intravenous infusion of rhHGF enhances the growth and function of the remnant liver in rats with cirrhosis after partial hepatectomy. Therefore, rhHGF may be useful after hepatic resection in patients with cirrhosis.

Animals↗

PubMed1997

Induction of hepatocyte growth factor activator messenger RNA in the liver following tissue injury and acute inflammation.

Hepatocyte growth factor activator (HGFA) is a serine protease that is responsible for localized activation of hepatocyte growth factor (HGF) in injured tissue. The activated HGF may be involved in regeneration of the injured tissue. HGFA is produced and secreted by the liver and circulates in the plasma as an inactive zymogen. In response to tissue injury, the HGFA zymogen is converted to the active form by limited proteolysis. In this study, we isolated a rat HGFA complementary DNA (cDNA) clone and analyzed the production of HGFA messenger RNA (mRNA) in response to tissue injury using this cDNA clone as a probe. The nucleotide sequence of the cDNA revealed that the amino acid sequences of rat and human HGFA showed a high degree of conservation in the regions of the characteristic domain structures, suggesting that rat and human HGFA are activated by a similar mechanism and have similar enzymatic activities in vivo. Tissue distribution analysis showed that the liver was the major site of rat HGFA mRNA synthesis. Moreover, the cells producing HGFA mRNA were identified as parenchymal liver cells. The level of HGFA mRNA increased in the liver after hepatotoxin or nephrotoxin treatment. This increase was also observed during acute inflammation induced by turpentine. These results suggest that the increase in production of HGFA mRNA in response to tissue injury is the result of an inflammatory response, and that HGFA is an acute phase protein.

Acute Disease↗

PubMed1997

The effects of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet.

Abundant fat in the liver has been implicated in poor outcome after liver transplantation or liver surgery, but the reasons for this association are still unclear. The aim of the present study was to examine mechanisms that may be involved in hepatic dysfunction after ischemia-reperfusion (I/R) of the steatotic rat liver. Steatosis was produced by a choline-methionine-deficient (CMDD) diet. In the first experiment, isolated perfused rat livers, subjected to 24-hour cold storage followed by 120-minute reperfusion, were used to investigate hypothermic I/R injury of the steatotic rat liver. In the second experiment, livers were subjected to 60-minute partial left lobar vascular clamping to allow study of normothermic I/R injury. In the first experiment, compared with normal nonsteatotic liver, steatotic livers showed significantly greater injury, as assessed by amounts of hepatic enzymes released into the perfusate, bile production, the concentrations of reduced glutathione (GSH) in the perfusate, as well as in the livers themselves, and electron microscopic findings of sinusoidal microcirculatory injury. The addition of N-acetylcysteine (NAC), a precursor of glutathione, to the liver before cold storage significantly improved these parameters in steatotic livers. The second experiment showed that, compared with nonsteatotic livers, steatotic livers had lower concentrations of GSH and impaired rates of bile production. There was also evidence of increased oxidative stress in polymorphonuclear leukocytes (PMNLs) in liver or peripheral blood of rats with fatty livers. An anti-rat intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody inhibited neutrophil infiltration into pericentral sinusoids and improved these parameters in the steatotic rats. We conclude that sinusoidal microcirculatory injury is involved in hypothermic I/R injury, that oxidative stress produced by PMNLs is involved in normothermic I/R injury, and that NAC and anti-rat ICAM-1 monoclonal antibody restore liver integrity in I/R injury.

Acetylcysteine↗

PubMed1997

A monoclonal antibody against ICAM-1 suppresses hepatic ischemia-reperfusion injury in rats.

Since intercellular adhesion molecule-1 (ICAM-1) has been reported to play a major role in reperfusion injury after ischemia, we estimated the effects of an anti-rat ICAM-1 monoclonal antibody (1A29) on hepatic ischemia-reperfusion injury in rats. Partial liver ischemia was achieved by clamping hepatic hilar vessels supplying the cephalad three lobes of the liver for 90 min. An intraportal injection of 1A29 was given 5 min after revascularization (n = 28), and saline was injected in control rats (n = 28). Changes in the proportion of liver necrosis, hepatic tissue blood flow, serum liver enzymes and liver neutrophil sequestration were analyzed at 6, 24, 48 and 72 h after revascularization. The intraportal injection of 1A29 significantly reduced the hepatocellular necrosis, restored the hepatic tissue blood flow at 24, 48 and 72 h of reperfusion (p < 0.05 or p < 0.01), and significantly suppressed the levels of serum liver enzymes at all time points during reperfusion (p < 0.01, respectively). The 1A29 treatment significantly reduced the number of neutrophils at the pericentral area, while those at the periportal area were similar in the two groups. The results suggested that ICAM-1 plays an important role in the development of hepatic ischemia-reperfusion injury, and that 1A29 reduced the injury possibly caused by cytotoxic inflammatory responses, based on neutrophil adherence to pericentral sinusoids.

Alanine Transaminase↗

PubMed1997

Production and activation of hepatocyte growth factor during the healing of rat gastric ulcers.

The hepatocyte growth factor has been reported to be a potent mitogen of various epithelial cells, including gastric mucosal cells. Therefore, production and activation of hepatocyte growth factor in the gastric wall were investigated to speculate on the possible role of this factor in the healing of gastric ulcer in rats. Indomethacin-induced gastric mucosal lesions and acetic acid induced ulcers were employed as models of acute gastric lesions and chronic ulcer, respectively. Immunoblot and Northern blot analyses indicate that experimentally induced gastric mucosal lesions stimulate not only the production of hepatocyte growth factor, but also the conversion to its active form. This conversion was accompanied by increased gene expression of hepatocyte growth factor activator in the stomach. In rats with acute mucosal lesions, hepatocyte growth factor activator mRNA was most abundant 6 h after induction of mucosal lesions. On the other hand, hepatocyte growth factor and hepatocyte growth factor activator mRNA levels were elevated until 15 days after the induction of chronic ulcers. In summary, it has been clarified that not only production, but also activation of hepatocyte growth factor is stimulated during gastric ulcer healing.

Animals↗

PubMed1997

Effects of ethyl alpha-D-glucoside on skin barrier disruption.

Daily treatments of skin in hairless mice with concentrates of rice wine, Japanese traditional alcohol, lowered transepidermal water loss levels compared to the controls on the 3rd day after ultraviolet B (UVB) irradiation. These findings indicate that the concentrates of rice wine suppress the murine skin barrier disruption caused by UVB. Ethyl alpha-D-glucoside (alpha-ethylglucoside), one of the peculiar components in rice wine, showed the same effect, whereas beta-ethylglucoside had no effect. In order to clarify the functions of alpha-ethylglucoside on murine skin, we examined the effects of this compound on the expression of some phenotypes in human keratinocytes in vitro. As a result, alpha-ethylglucoside as well as beta-ethylglucoside enhanced cell proliferation weakly, and the formation of cornified envelopes and differentiated type keratin (K1) in keratinocytes was accelerated by alpha-ethylglucoside but not by beta-ethylglucoside. From the results, we conclude that alpha-ethylglucoside enhanced the differentiation of keratinocytes, which might be related to reduced barrier disruption by UVB.

Alcoholic Beverages↗

PubMed1997

Cysteine-S-conjugate beta-lyase activity and pyridoxal phosphate binding site of onion alliin lyase.

Purification of onion alliin lyase gave two fractions by cation exchange chromatography. Both fractions showed the comparable high catalytic activity of cysteine-S-conjugate beta-lyase with that of alliin lyase using S-(2-chloro-6-nitrophenyl)-L-cysteine and alliin, S-allyl-L-cysteine sulfoxide as substrates. All the active substrates tested with onion alliin lyase were also active to the cysteine-S-conjugate beta-lyase of Mucor javanicus, but the catalytic activity of the Mucor enzyme was lower for all the substrates. The pyridoxal phosphate binding site of the onion alliin lyase was identified as Lys 285 in the amino acid sequence deduced from cDNA which has been reported. This lysine was conserved in all the sequences from the alliin lyase cDNAs, while similarity was not found between the sequences around pyridoxal phosphate binding sites of both the onion alliin lyase and the Mucor cysteine-S-conjugate beta-lyase.

Allium↗

PubMed1997

Histological study of the seminiferous epithelium in the Japanese rat snake, Elaphe climacophora: identification of spermatogonium.

To clarify the features of the seminiferous epithelium of the Japanese rat snake, Elaphe climacophora, the identification of spermatogonium and the examination of features of cell to cell junctions were performed in the present study. As for the identification, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined immunohistochemically to mark spermatogonia. The seminiferous epithelium was observed throughout a year at the electron microscopic level. BrdU immunoreactivity was detected not only in the cells of the first layer of the seminiferous epithelium but also in the second and/or third layers. The cells immunoreactive in the first layer did not seem to attach to the basement membrane and were recognized throughout a year. To investigate cell to cell junctions, we performed actin filament detection by phalloidin staining. Distribution of actin filaments was different from that in mammalian species. At the ultrastructural level, Sertoli-Sertoli cell junctions were observed. Sertoli cells formed junctional complexes. Tight junctions were clearly found, but lacked the backing by actin filaments. These results indicate that the blood-testis barrier of the Japanese rat snake was structurally different from that of mammalian species. In conclusion, the seminiferous epithelium of the Japanese rat snake is intermediate in morphology between amphibians and mammals.

Actins↗

PubMed1997

[Effects of fibronectin on the monokine production by cultured-human monocytes].

The effect of fibronectin (FN) on IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by ELISA. FN markedly stimulated the secretion of IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6 from cultured monocytes. Northern blot analysis revealed the up-regulated expression of mRNA specific for each monokine on exposure of monocytes to FN. GM-CSF, IFN-gamma, and LPS synergistically enhanced FN-induced IL-1 alpha production. We further investigated the signal transduction pathways involved in FN-stimulated monokine secretion. FN-stimulated TNF-alpha secretion was markedly inhibited by either herbimycin A or genistein, inhibitors of protein tyrosine kinase (PTK), but was not affected by staurosporin, a inhibitor of protein kinase C (PKC). The results suggest that PTK is required for FN-stimulated TNF-alpha secretion. In contrast, LPS-stimulated TNF-alpha secretion was markedly inhibited by not only herbimycin A or genistein, but also staurosporin. Therefore, both PTK and PKC may be involved in LPS-stimulated TNF-alpha secretion. We also demonstrated that, in monocytes, cytoplasmic proteins of about 70 and 240 kDa were phosphorylated after FN stimulation. Our results indicate that FN may contribute to the inflammatory response of monocyte by inducing monokine production.

Cells, Cultured↗

PubMed1997

[Arterial-venous carbon dioxide tension difference after hypothermic cardiopulmonary bypass].

Arterial-venous carbon dioxide tension difference (Pv-aCO2) is known to become high after severe hemorrhage shock and resuscitation. We hypothesized that Pv-aCO2 might be high after cardiac surgery because of the oxygen debt occurred during hypothermic cardiopulmonary bypass (CPB). Blood pressure, cardiac index, hemoglobin, the arterial and mixed venous blood gases were repeatedly measured every 6 hours for 24 hours following cardiac surgery in 60 adult patients who underwent hypothermic CPB. Immediately after the surgery, Pv-aCO2 was extremely high, then gradually decreased to within normal ranges 12 hours later (8.0 +/- 2.9 mmHg vs 5.9 +/- 3.1 mmHg. p < 0.01). Factors which significantly correlated to Pv-aCO2 were cardiac index, oxygen delivery, minimum rectal temperature and duration of CPB. Oxygen debt during hypothermic CPB might cause significantly high Pv-aDO2. At least 12 hours were necessary to recover from anaerobic status to physiological condition.

Adult↗

PubMed1997

Prediction of postoperative decompensated liver function by technetium-99m galactosyl-human serum albumin liver scintigraphy in patients with hepatocellular carcinoma complicating chronic liver disease.

BACKGROUND: Preoperative technetium-99m galactosyl-human serum albumin (Tc-GSA) liver scintigraphy may predict postoperative decompensated liver function and its value has been investigated in patients having resection of hepatocellular carcinoma (HCC). METHODS: Hepatic uptake ratio of Tc-GSA (LHL15) was measured before operation in 30 patients. Postoperative complications were analysed retrospectively and compared with LHL15 values and other indicators evaluating hepatic function. RESULTS: The LHL15 of 22 patients without complications was 0.91 or more, compared with 0.90 or less in the eight patients who had complications. Multifactorial analyses showed that LHL15 and Child-Pugh grade significantly predicted postoperative complications (P < 0.0001 and P = 0.0111 respectively). LHL15 was a significant predictor of complications in patients with Child-Pugh grade B disease (n = 15, P = 0.0011). CONCLUSION: LHL15 was a reliable preoperative indicator of the risk of major postoperative complications in patients who had resection for HCC.

Aged↗

PubMed1997

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1995)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by 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, 567 strains of presumably etiological bacteria were isolated mainly from the sputa of 459 patients with lower respiratory tract infections during the period from October 1995 to September 1996. MICs of various antibacterial agents and antibiotics were determined against 74 strains of Staphylococcus aureus, 82 strains of Streptococcus pneumoniae, 104 strains of Haemophilus influenzae, 85 strains of Pseudomonas aeruginosa (non-mucoid strains), 18 strains of Pseudomonas aeruginosa (mucoid strains), 52 strains of Moraxella subgenus Branhamella catarrhalis, 25 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 (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 52.7%. Arbekacin (ABK) showed the most highest activity against S. aureus with MIC80 of 0.5 micrograms/ml. Vancomycin (VCM) showed the next highest activity with MIC80 of 1 microgram/ml. These drugs showed the high activities against MRSA with MIC80S of 1 microgram/ml. 2) S. pneumoniae. Most of drugs tested showed potent activities against S. pneumoniae. Imipenem (IPM) and panipenem (PAPM), carbapenems, showed the most potent activity with MIC80S of 0.063 microgram/ml. Cefotaxime (CTX), cefmenoxime (CMX) and cefpirome (CPR) of cephems showed the next most potent activities with MIC80S of 0.25 microgram/ml. Erythromycin (EM) and clindamycin (CLDM) showed low activities with MIC80S 128 micrograms/ml or high. Among these strains, however, 48.8% and 65.9% of respective strains were quite toward sensitive these agents with MICs of 0.063 microgram/ml. 3) H. influenzae. The activities of all drugs were potent against H. influenzae test with all MICs at 4 micrograms/ml or below. Cefotiam (CTM), CMX, cefditoren (CDTR) and ofloxacin (OFLX) showed the most potent activity with MIC90S to 0.063 microgram/ml. 4) P. aeruginosa. (mucoid strains) IPM and tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80S of 1 microgram/ml. Ceftazidime (CAZ), cefsulodin (CFS) and carumonam (CRMN) showed next potent activity, with MIC80S of 2 micrograms/ml. The MIC80S of the other drugs ranged from 4 micrograms/ml to 32 micrograms/ml. 5) P. aeruginosa (non-mucoid strains). TOB and ciprofloxacin (CPFX) showed the most potent activities against P. aeruginosa (non-mucoid strains) with MIC80S of 1 microgram/ml. The MIC80 of ampicillin (ABPC) was 128 micrograms/ml in 1994, it was 16 micrograms/ml in 1995. 6) K. pneumoniae. All drugs except ABPC were active against K. pneumoniae. CPR and CRMN showed the most potent activities against K. pneumoniae with MIC80S of 0.063 microgram/ml. The MIC80S of the other drugs ranged from 0.125 microgram/ml to 2 micrograms/ml. 7) M. (B.) catarrhalis. Against M. (B.) catarrhalis, all the drugs showed good activities with MIC80S at 4 micrograms/ml or below. And MICs of all strains were 8 micrograms/ml or below. IPM, OFLX and minocycline (MINO) showed the most potent activity with MIC80S of 0.063 microgram/ml. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. Patients' backgrounds were examine for 567 isolates from 459 cases. The examination of age distribution found that the proportion of patients with ages over 60 years was 66.3% of all the patients showing a slight increase over that in 1994. Proportion of differe

Adolescent↗