Superconductivity in the metal rich Li-Pd-B ternary boride.

Superconductivity at about 8 K was observed in the metal-rich Li-Pd-B ternary system. Structural, microstructural, electrical, and magnetic investigations for various compositions proved that the Li2Pd3B compound, which has an antiperovskite cubic structure composed of distorted Pd6B octahedrons, is responsible for the superconductivity. This is the first observation of superconductivity in metal-rich ternary borides containing alkaline metal and Pd as a late transition metal. The compound prepared by arc melting has a high density and is relatively stable in the air. The upper critical fields H(c2)(0) estimated by linear extrapolation and the Werthamer-Helfand-Hohenberg theory are 6.2 and 4.8 T, respectively.

Enhanced expression of heat shock proteins in activated polymorphonuclear leukocytes in patients with sepsis.

BACKGROUND: Heat shock proteins (HSPs) in cells, as molecular chaperons, have been reported to regulate cell functions. The objective of this study was to investigate the HSP expression in polymorphonuclear leukocytes (PMNLs) from severe septic patients and the relation between the expression of HSPs and PMNL function. METHODS: In blood samples from 21 patients with sepsis and serum C-reactive protein levels more than 10 mg/dL, we used flow cytometry to measure expressions of HSP27, HSP60, HSP70, and HSP90; oxidative activity; and levels of apoptosis in PMNLs during sepsis. In in vitro studies, we used cells from 14 healthy volunteers to examine the relation between the expression of HSP70 and PMNL function. Quercetin (30 microM), a suppressor of HSP, and sodium arsenite (100 microM), an inducer of HSP, were used to regulate the expression of HSP70 in PMNLs, and oxidative activity and apoptosis in these cells were measured. RESULTS: In patients with sepsis, the expressions of HSP27, HSP60, HSP70, and HSP90 and oxidative activity in PMNLs were significantly increased. Apoptosis of these PMNLs was markedly inhibited. In the in vitro studies, administration of sodium arsenite enhanced the expression of HSP70, significantly increased oxidative activity, and inhibited apoptosis. Administration of quercetin before sodium arsenite prevented the expression of HSP70, the increase in oxidative activity, and the inhibition of apoptosis. CONCLUSION: Sepsis causes the enhanced expression of HSPs in activated PMNLs. In PMNLs with enhanced expression of HSP70, oxidative activity is increased and apoptosis is inhibited. The enhanced expression of HSPs may play a role in regulating PMNL function in patients with sepsis.

Granulocyte colony-stimulating factor (G-CSF) stiffens leukocytes but attenuates inflammatory response without lung injury in septic patients.

OBJECTIVE: To determine whether granulocyte colony-stimulating factor (G-CSF) administration changes leukocyte deformability resulting in lung injury in patients with sepsis. METHODS: Twenty-five consecutive septic patients were divided randomly into two groups. Twelve patients were given recombinant human G-CSF subcutaneously at 2 microg/kg once a day for 5 days (group G). The remaining 13 patients were given sterilized saline as placebo (group N). Leukocyte count; concentrations of C-reactive protein (CRP) and thrombomodulin (TM); respiratory index (RI) and lung injury score (LIS); and APACHE II score and Goris MOF index were determined before and after G-CSF or placebo administration. Leukocyte deformability was observed in a microchannel array etched on a single-crystal silicon tip, which simulates the microvasculature. The number of microchannels obstructed (NOM) by stiffened leukocytes was counted. Transit time (TT), that is, the time taken for 100 microL of whole blood to pass through the microchannel, was determined. RESULTS: G-CSF administration significantly increased leukocyte count and decreased CRP concentration. In group G, both NOM and TT increased significantly 5 days after G-CSF administration; they did not change in group N. However, RI, LIS, and TM did not change, suggesting that no patient developed lung injury. CONCLUSION: G-CSF causes leukocyte stiffness but attenuates inflammatory response without inducing lung injury in septic patients.

A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure. Mild Hypothermia Study Group in Japan.

OBJECT: The criteria for the use of mild hypothermia (34 degrees C) in severely head injured patients have not been standardized. A prospective randomized controlled trial was conducted to determine whether mild hypothermia is essential in the treatment of severely head injured patients with low intracranial pressure (ICP). METHODS: At 11 medical centers, 91 severely head injured patients with an admission Glasgow Coma Scale score of 8 or less in whom ICP could be maintained below 25 mm Hg by conventional therapies were divided randomly into two groups: the mild hypothermia group (HT group, 45 patients) and the normothermia group (NT group, 46 patients). Patients in the HT group were exposed to mild hypothermia (34 degrees C) for 48 hours, followed by rewarming at 1 degrees C per day for 3 days, whereas patients in the NT group were exposed to normothermia (37 degrees C) for 5 days. The two groups were similar with respect to prognostic factors, and there was no difference in clinical outcome at 3 months postinjury. During treatment, there was a significantly greater use of neuromuscular blocking agents in the HT group (p = 0.011). During the initial 2 weeks postinjury, the incidences of pneumonia, meningitis, leukocytopenia, thrombocytopenia, hypernatremia, hypokalemia, and hyperamylasemia were significantly higher in the HT than in the NT group (p < 0.05). CONCLUSIONS: Mild hypothermia should not be used for the treatment of severely head injured patients with low ICP because this therapy conveys no advantage over normothermia in such patients.

Difference in the responses after administration of granulocyte colony-stimulating factor in septic patients with relative neutropenia.

OBJECTIVE: The objective of this study was to classify the clinical responses after administration of granulocyte colony-stimulating factor (G-CSF) in septic patients with relative neutropenia. PATIENTS AND METHODS: We administered recombinant human G-CSF (2 microg/kg) subcutaneously once a day for 5 days to 30 septic patients with white cell counts below 5,000 cells/mm3. Absolute neutrophil count (ANC), neutrophil differentiation, and serum concentration of G-CSF were determined serially. Bone marrow also was analyzed before and after treatment. RESULTS: Neutrophil responses to G-CSF varied from good (ANC > 10,000/mm3, group G, n = 20) to moderate (ANC < 10,000/mm3, group M, n = 5) to poor (no increase in ANC, group P, n = 5). Before G-CSF administration, the three groups showed no differences in ANC but did show significant differences in serum concentration of G-CSF. G-CSF concentration was 0.16 +/- 0.03 ng/mL in group G, 7.0 +/- 3.0 ng/mL in group M, and 270 +/- 90 ng/mL in group P. Immature neutrophils accounted for 35.0 +/- 3.7% of peripheral leukocytes in group P but only 5.1 +/- 0.6% in group G. Although bone marrow was depressed in all groups before G-CSF treatment, nucleated cell count increased significantly after rhG-CSF treatment in groups G and M. Survival rate after 4 weeks was 90% in group G and 100% in group M; no patient in group P survived. CONCLUSION: G-CSF administration was effective in septic patients with a low percentage of immature neutrophils and insufficient endogenous G-CSF. It had little effect on patients with a high percentage of immature neutrophils whose G-CSF production was up-regulated and whose bone marrow was severely depressed.

Burn injuries in the 1995 Hanshin-Awaji earthquake.

In the 1995 Hanshin-Awaji earthquake, 504 deaths were listed as fire related, although many of the victims may have been crushed or suffocated before they were burned. Census data related to surviving burn victims, however, were unknown. This study was designed to examine the medical requirements of those burn patients following the earthquake. Medical records of 2718 patients with injuries admitted to 95 hospitals during the 15 days after the earthquake were retrospectively reviewed. Only 44 patients (1.9 per cent) were hospitalized with burns. Scalds with less than 20 per cent total burn surface area (TBSA) were mainly observed; flame burns from earthquake-associated fires were rare. Morbidity rates increased in patients over 40 years old. Associated injuries were observed in 11 cases. These included three soft tissue injuries, one rib, three spine, three pelvis and two extremity fractures, and two cases of crush syndrome. Intensive care was required for only 10 patients, five of whom were transferred to hospitals that were undamaged or outside the earthquake zone. No relationship was noted between the number of burned houses and that of hospitalized burn patients. These results suggest that the number of burn patients requiring medical care was less than might have been expected in view of the total number of fire-related deaths in this urban earthquake.

[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

[A family outbreak of Chlamydia psittaci infection].

A family outbreak (3 cases) of Chlamydia psittaci infection was reported. The first case, a 56-year-old man was admitted with fever and general fatigue. Chest X-ray film revealed a consolidation in the right lower lung. One month before admission he had purchased 2 parakeets (chick) and one parakeet died. On learning of his history of contact with the chick, psittacosis was suspected. After administration of fixation (CF) antibody titer against chlamydia rose to 1:128 and IgA titer against Chlamydia psittaci by microimmunofluorescence antibody technique (MAF) rose to 1:128 in 21 days after admission. The second case, the wife of the first, a 53-year-old woman had a fever and a cough about two weeks before the admission of the first case. At the time of her husband was admitted, she attended the outpatient department. The chest CT X-ray film showed a ground glass appearance in both lower lung fields. The third case, the daughter of the first, didn't have any signs. Chest X-ray film was normal. But IgM titer against Chlamydia psittaci by MAF rose to 1:16 and IgA titer against Chlamydia psittaci by MAF rose to 1:128. This case was considered as inapparent infection.

[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)

[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

[Intractable respiratory infections].

Silent aspiration would be major factor which predispose the bacterial infections in aged patients. Sixty-seven strains were isolated from culture positive cases. Anaerobes, S. pneumoniae, S. aureus, P. aeruginosa were the more frequently isolated strains of bacteria. Gram-negative rods were apparent in 39%, and Anaerobes were 19%, of 67 strains. Patients with diffuse panbronchiolitis are frequently affected by P. aeruginosa superinfection. The patients with longer duration, more severe lung function and more deteriorated roentgenological findings developed P. aeruginosa superinfection more easily. These infection in the lower respiratory tract significantly affect the prognosis of DPB patients. Using long-term administration of erythromycin against DPB, acute exacerbation were controlled in some patients and the frequency of their admission to hospital was lessened.

Paroxysmal nocturnal hemoglobinuria with myelofibrosis: progression to acute myeloblastic leukemia.

A 58-year-old male was diagnosed as having paroxysmal nocturnal hemoglobinuria (PNH) with myelofibrosis in 1984. The administration of hydroxyurea and low dose splenic irradiation were initiated for abdominal distention due to splenomegaly in 1987. In May 1990 the patient developed smouldering acute myeloblastic leukemia (AML); and the blasts proliferated in response to G-CSF administered for refractory pneumonia. The patient died of pneumonia and pleural involvement of leukemia in September 1990. FACS analysis of the blasts using anti-decay accelerating factor (DAF) (CD55) and CD59 (membrane attack complex inhibition factor: MACIF) monoclonal antibodies demonstrated that 25.5% and/or 87.3% of the blasts were negative for DAF or CD59 respectively. There is the earlier evidence that about 90% leukemic myeloblasts from non-PNH AML patients are positive for DAF, and nearly 100% of non-PNH neutrophils have been shown to be positive for both DAF and CD59. Our data suggest that the leukemic blasts from this patient may have derived from the PNH clone.

[A case of Legionella pneumonia with myelodysplastic syndrome].

A 40-year-old man was admitted with high fever and cough. Pneumonic shadows of the left middle and lower lung fields increased rapidly, and his blood gases worsened. Initial treatment with cefmenoxime, piperacillin, and minocycline was ineffective. Administration of rifampicin was started for suspected legionella pneumonia, but it did not control the spread of the pneumonia shadows. After addition of an antifungal agent and trimethoprim-sulfamethoxazole, his symptoms gradually improved. Isolation of Legionella pneumophila from sputum specimens collected on the 4th day of admission confirmed the diagnosis on day 10. The patient was then given oral rifampicin plus cefmenoxime to prevent mixed infection, and showed a satisfactory improvement. Legionella pneumonia developed secondary to compromise of the patient's immunity due to steroid therapy for MDS. After recovering from Legionella pneumonia, the patient subsequently developed tuberculous pleurisy and Pneumocystis carinii pneumonia, which were cured by antituberculous therapy and trimethoprim-sulfamethoxazole. However, acute hepatitis followed by hepatic failure developed, and he died on day 121 after admission.

[Sputum penetration of levofloxacin and its clinical efficacy in patients with chronic lower respiratory tract infections].

Sputum penetration of levofloxacin (LVFX) was evaluated after a single oral dose of 100 mg or 200 mg to 4 patients with copious purulent sputa. The sputum concentration of LVFX reached maximum levels of 1.27 and 4.36 micrograms/ml at 4 hours, and still remained at concentrations of 0.32 and 1.68 micrograms/ml at 8 hours after administration of 100 mg and 200 mg, respectively. The AUC ratio of sputum/serum was 0.9-1.0, indicating good sputum penetration of LVFX in these patients. The clinical efficacy and the safety of LVFX were also evaluated in a total of 13 patients with respiratory tract infections associated with bronchiectasis, diffuse panbronchiolitis, etc. LVFX was administered orally at a daily dose of 200 mg once a day, 100 mg t.i.d. or 200 mg t.i.d. for 7-28 days (mean 14.7 days). The clinical response to the drug was rated as excellent in 1 case, good in 5, fair in 3, and poor in 2 cases in 11 evaluable cases, thus the efficacy rate was 54.5%. All the 3 strains of Haemophilus influenzae were eradicated. Of the 3 strains of Pseudomonas aeruginosa, eradication, decrease, and unchange was observed for 1 strain each. One strain of Streptococcus pneumoniae remained unchanged. No adverse reaction was observed except for 1 case with slight and temporary increase of eosinophils. The above results suggested that LVFX would be clinically useful in the treatment of chronic lower respiratory tract infections.

The carboxyl terminal amino acid residues of Pseudomonas aeruginosa exotoxin A involved in cell toxicity and pathogenesis, characterized by a neutralizing human monoclonal antibody.

Human monoclonal antibody HI-1A4 (IgG3, lambda) neutralized a toxicity caused by pseudomonal exotoxin A (Ex-A) in cell culture and in vivo, and was effective in experimental Pseudomonas aeruginosa infections in mice. HI-1A4 inhibited an Ex-A catalyzed ADP-ribosylation of elongation factor 2 but did not inhibit an incorporation of toxin into a target cell at all. One molecule of HI-1A4 neutralized at least 2 molecules of Ex-A. HI-1A4 retained its binding activity at pH 4.0. The epitope region for HI-1A4 was demonstrated to be a carboxyl terminal end of amino acid residues 591-613 of Ex-A. HI-1A4 might bind to Ex-A carboxyl terminal region outside a target cell, be incorporated into cells as a complex with Ex-A, and inhibit the intracellular function in which the carboxyl terminal part of Ex-A was involved, resulting in the interruption of intoxication of Ex-A.