Factors Associated With Physical Restraints in a Psychiatric Unit in Japan: a Retrospective Study.

OBJECTIVE: To identify factors associated with the use and duration of physical restraint (PR) in a psychiatric unit in Japan. METHODS: Medical records of 1308 patients admitted first time to the psychiatric emergency unit of Showa University Northern Yokohama Hospital between 1 January 2014 and 31 December 2021 were retrospectively reviewed. Data collected included patient age, sex, outpatient treatment, living arrangements, disability pension status, diagnosis (based on ICD-10), and psychotropic medication use at admission (chlorpromazine equivalent dose, imipramine equivalent dose, diazepam equivalent dose, and number of mood stabilisers administered). Logistic regression analysis and multiple regression analysis were used to identify factors associated with the use and duration of PR, respectively. RESULTS: Of 1308 patients, 399 (30.5%) were subjected to PR and 909 (69.5%) were not. Among the 399 patients subjected to PR, 54 were excluded from the multiple regression analysis for duration of PR as they remained subject to PR on the day of discharge. The remaining 345 patients were subject to PR for a median of 10 days. PR utilisation was associated with male sex (odds ratio [OR] = 1.420), treatment at our hospital (OR = 0.260), treatment at other hospitals (OR = 0.645), F3 diagnosis (depression) [OR = 0.290], F4-9 diagnosis (OR = 0.309), and imipramine equivalent dose at admission (unit OR = 0.994). The log-transformed duration of PR was independently associated with the age group of 50 to 69 years (ß = 0.248), the age group of ≥70 years (ß = 0.274), receiving a disability pension (ß = 0.153), an F1 diagnosis (ß = -0.187), an F4-9 diagnosis (ß = -0.182), chlorpromazine equivalent dose at admission (ß = 0.0004), and number of mood stabilisers administered at admission (ß = -0.270). CONCLUSION: Identifying factors associated with the use and duration of PR may lead to reduction in the use and duration of PR.

Intracellular Localization of Mycoplasma bovis in the Bronchiolar Epithelium of Experimentally Infected Calves.

Lung tissues from calves infected experimentally with Mycoplasma bovis were examined by immunohistochemistry and electron microscopy. All inoculated calves had dark red areas of consolidation affecting both left and right lungs, which were characterized microscopically by subacute purulent bronchiolitis with hyperplasia of the surrounding lymphoid tissue. Immunohistochemically, M. bovis antigen was detected on the surface and inside the cytoplasm of bronchiolar epithelial cells in the pneumonic foci. The antigen was also found in the cytoplasm of phagocytes at the margin of bronchiolar exudates. Electron microscopically, numerous organisms were demonstrated in the immunohistochemically-positive sites. These findings suggest that M. bovis organisms adhere to the bronchiolar epithelium and at least some of them invade the epithelium.

Functional outcomes and patient satisfaction after vascularized osteocutaneous scapula flap reconstruction of the mandible in patients with benign or cancerous tumours.

Pre- and postoperative longitudinal assessment of oral functions including masticatory force, masticatory ability with solids, speech intelligibility, and subjective satisfaction was conducted for patients who underwent vascularized osteocutaneous scapula flap reconstruction after mandibulectomy. Postoperative changes in oral function and patient satisfaction were examined in relation to tumour type (i.e., cancerous vs. benign). A change in masticatory force was associated with a reduction in the number of occlusal support zones after surgery and clearly differed by tumour type. Despite all patients showing reduced masticatory force postoperatively, all were satisfied with the improvements in eating and chewing, which were greater in patients with benign tumours than in those with cancerous tumours. Although both groups of patients expressed satisfaction with the aesthetic appearance after surgery, patients with cancerous tumours were more satisfied. However, both groups showed decreased speech intelligibility scores and lower satisfaction with speech after surgery. Preoperative support in the form of reassurance and helping to alleviate anxiety about postoperative appearance would be beneficial for all patients, with additional support provided based on the specific tumour type.

Correlation between variable-number tandem-repeat-based genotypes and drug susceptibility in Mycobacterium avium isolates.

Little is known about the correlation between genotype and drug susceptibility in Mycobacterium avium (Mav) strains isolated from patients with Mav infections. To examine whether drug susceptibility profile of Mav is associated with genotype, we carried out variable-number tandem-repeat (VNTR) typing and drug susceptibility testing for Mav isolates from Japanese with nodular-bronchiectasis (NB)-type and cavitary disease (CA)-type diseases. We performed M. avium tandem repeat (MATR)-VNTR typing and drug susceptibility testing by the broth dilution method, using macrolides, rifamycins, ethambutol, isoniazid, aminoglycosides, and quinolones, for Mav isolates from patients with NB and CA-type diseases (NB-Mav and CA-Mav). Based on the VNTR genotyping, the Mav strains were grouped into three clusters. There was no difference with respect to the distribution of NB-Mav and CA-Mav among the clusters. We observed a strong association between VNTR genotype and susceptibility to quinolones (levofloxacin, moxifloxacin, gatifloxacin, sitafloxacin, and garenoxacin) and ethambutol. There was essentially no significant difference in drug susceptibility between NB- and CA-Mav strains, although NB-Mav was somewhat more resistant to fluoroquinolones, especially gatifloxacin, than CA-Mav. There was a significant association between VNTR genotype and susceptibility to quinolones and ethambutol in Mav isolates from Japanese patients.

High performance RO membranes for desalination and wastewater reclamation and their operation results.

Reverse osmosis (RO) membrane is one of the most powerful tools for solving the global water crisis, and is used in a variety of water treatment scenes such as drinking water purification, waste-water treatment, boiler feed water production, ultra pure water production for semiconductor industry, etc. The desired performance of RO membrane varies according to quality of feed water being treated, and Toray has been developing RO membranes with suitable characteristic for each operating condition. RO membranes for seawater desalination and wastewater reclamation are especially regarded as most promising targets. Recently, high boron removal and energy saving RO membrane for seawater desalination and low fouling RO membrane for wastewater reclamation have been developed. In this paper, the prospect of attaining these renovative RO membrane, and furthermore, job references will be discussed.

Comparative study for the virulence of Mycobacterium avium isolates from patients with nodular-bronchiectasis- and cavitary-type diseases.

Mycobacterium avium (Mav) lung infections, called nodular-bronchiectasis (NB)-type M. avium complex (MAC) disease, are globally increasing. To elucidate whether there are unusual populations of Mav, causing NB-type disease rather than cavitary (CA)-type disease, we compared the virulence of Mav isolates from patients with NB-type (NB-Mav) and those from CA-type (CA-Mav) diseases, based on intracellular growth in various types of human cells. Five strains each of NB-Mav and CA-Mav were compared with each other for their invasiveness and ability to intracellularly replicate in various types of cultured cells of human origin. The two types of Mav isolates showed a similar ability, on average, to replicate in macrophages and lung epithelial cells. Moreover, they showed a similar ability to induce the production of reactive nitrogen intermediates and reactive oxygen intermediates by macrophages and susceptibility to antimicrobial molecules. Therefore, it appears that there is no essential difference in virulence in terms of infectivity to human macrophages and lung cells between Mav strains isolated from NB-MAC disease and those from CA-MAC disease. These findings indicate the importance of further studies to elucidate the mechanism for the establishment of NB-type MAC diseases based on host immunological conditions rather than the pathogenic nature of MAC organisms themselves.

[Effectiveness of high frequency jet ventilation introduced immediately after cardiac surgery].

It is important to establish the lung protective strategy strictly for serious respiratory failure after cardiac surgery, because the hemodynamic state is unstable. High frequency jet ventilation (HFJV) was introduced in 5 patients with respiratory failure after cardiac surgery. Two had been diagnosed with acute aortic dissection and 3 with angina pectorlis. Off pump coronary artery bypass grafting was performed in 2 patients. Hemodynamic variables during HFJV were stable, and the duration of HFJV was 9 to 45 hours. Oxygenations improved immediately by the introduction of HFJV in all patients, and no adverse effect was recognized. Therefore, use of HFJV immediately after cardiac surgery might be an effective respiratory therapy of choice for patients with acute lung injury.

Should balloon-occluded retrograde transvenous obliteration be the first-line interventional radiologic treatment for bleeding duodenal varices? A case report and review of the literature.

We report a 78-year-old woman who presented with repeated tarry stools, and having lower duodenal variceal bleeding caused by portal hypertension. Endoscopic therapy had been attempted, but was impossible because the endoscope could not be inserted into the lower duodenum. Thus, the lower duodenal variceal bleeding was treated with balloon-occluded retrograde transvenous obliteration in combination with embolization using microcoils. Complete hemostasis was achieved without complications, and neither the recurrence of varices nor rebleeding has occurred for the last 3 years. A review of the English-language literature reveals only 11 such cases. The world literature is reviewed.

Acute cholecystitis due to strangulation of a floating gallbladder by the lesser omentum.

We report a unique case of acute cholecystitis due to strangulation of a floating gallbladder by the lesser omentum, which could be detected by abdominal ultrasonography. We believe this case to be the first case of reported literatures in English.

Comparative studies on the roles of mediator molecules in expression of the suppressor activity of Mycobacterium avium complex-induced immunosuppressive macrophages against T cell and B cell mitogenic responses.

Mycobacterium avium complex-induced immunosuppressive macrophages (MAC-MPhis) exhibit suppressor activity against concanavalin A-induced T cell mitogenesis (T cell Con A mitogenesis). We examined the profiles of the MAC-MPhi-mediated suppression of lipopolysaccharide-induced B cell mitogenesis (B cell LPS mitogenesis) and found the following. First, although N(G)-monomethyl-L-arginine and carboxy-PTIO effectively blocked the MAC-MPhi's suppressor activity against T cell Con A mitogenesis, MAC-MPhi's action against B cell LPS mitogenesis was only weakly affected by these NO-reducing agents. Second, B cell LPS mitogenesis was remarkably more susceptible to MAC-MPhi-derived reactive oxygen intermediates than T cell Con A mitogenesis. Third, B cell LPS mitogenesis was less susceptible to the inhibitory effects of the other MAC-MPhi-derived suppressor mediators, including free fatty acids, TGF-beta and prostaglandin E(2), than T cell Con A mitogenesis. Fourth, MAC-MPhi's suppressor activity was strongly dependent on B7-1 like molecule-mediated cell contact with target cells only in the case of T cell Con A mitogenesis. Therefore, there are significant differences in the modes of suppressor action of MAC-MPhis against T cell and B cell mitogenesis.

The role of B7 molecules in the cell contact-mediated suppression of T cell mitogenesis by immunosuppressive macrophages induced with mycobacterial infection.

We found previously that immunosuppressive macrophages (Mphis) induced by Mycobacterium intracellulare infection (MI-Mphis) transmitted their suppressor signals to target T cells through cell contact with target T cells. In this study, we examined what kinds of Mphi surface molecules are required for such cell-to-cell interaction. First, it was found that a B7-1-like molecule (B7-1LM) recognizable with one of three test clones of anti-B7-1 monoclonal antibodies (mAbs) was required for expression of the Mphi suppressor activity. Neither anti-B7-2, anti-ICAM-1, nor anti-VCAM-1 mAb blocked the Mphi suppressor activity. Second, MI-Mphis increased the expression of B7-1LM in parallel with the acquisition of the suppressor activity. Moreover, MI-Mphis bound with target T cells in a B7-1LM-dependent fashion. Third, mAb blocking of CTLA-4 on target T cells did not reduce the suppressor activity of MI-Mphis, suggesting the role of a putative molecule on target T cells other than CTLA-4 as the receptor for B7-1LM of MI-Mphis. Fourth, concanavalin A (Con A) stimulation of MI-Mphis was needed for effective cell contact with target T cells and subsequent expression of the suppressor activity of MI-Mphis. Fifth, the Con A-induced increase in the suppressor activity of MI-Mphis was inhibited by KN-62 but not by herbimycin A, H-7, nor H-88, indicating that Con A-induced up-regulation of MI-Mphi function is mediated by calmodulin-dependent protein kinase II or ATP/P2Z receptors, but independent of protein tyrosine kinase, protein kinase C, and protein kinase A. These findings indicate that a B7/CTLA-4-independent mechanism is needed for the transmission of the suppressor signals from MI-Mphis to target T cells.

Comparative roles of macrophages and NK cells in the host innate resistance of mice to Mycobacterium fortuitum infection.

OBJECTIVES: Profiles of host innate resistance to Mycobacterium fortuitum (MFT) infection in mice and the roles of macrophages (Mphis) and NK cells in host resistance to MFT infection were studied. METHODS: MFT-infected mice with or without the treatments to reduce Mphis and NK cells were examined for survival and the bacterial loads in the kidneys during the course of infection. RESULTS: A unique profile of strain difference was found in the innate resistance of mice to MFT. A/J, C3H/He and DBA/2 mice were susceptible, while BALB/c, B10A and C57BL/6 mice were resistant, in terms of survival after MFT infection. Such profiles of host resistance to MFT were essentially correlated with the ability of individual strain mice to prevent the bacterial growth in the early periods after infection. These profiles were different from the strain difference controlled by Bcg gene. Studies using carrageenan, anti-asialo GM1 antibody, and NK cell-deficient beige mice indicated the important roles of Mphis and NK cells in the host innate defense against MFT. CONCLUSIONS: These findings suggest that Bcg gene does not control the host resistance to MFT and that both Mphis and NK cells play crucial roles in the host innate resistance to MFT infection.

Comparative antimicrobial activities of gatifloxacin, sitafloxacin and levofloxacin against Mycobacterium tuberculosis replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines.

Mycobacterium tuberculosis (MTB) is capable of invading not only macrophages (Mphis) but also type II pneumocytes. In this study, we compared the antimicrobial activities of fluoroquinolones, including gatifloxacin, sitafloxacin and levofloxacin, against the MTB replication in the Mono Mac 6 human Mphi cell line (MM6-Mphis) and the A-549 human type II alveolar epithelial cell line (A-549 cells). When test quinolones were added at the MIC (0.125, 0.06 and 0.25 mg/l for gatifloxacin, sitafloxacin and levofloxacin, respectively) to the culture media of MTB-infected cells, these drugs exerted growth-inhibitory activity against intracellular organisms in the order of sitafloxacin > gatifloxacin > levofloxacin. On the other hand, when test quinolones were added at Cmax in the blood (1.7, 1.0 and 2.0 mg/l for gatifloxacin, sitafloxacin and levofloxacin, respectively), these drugs exhibited bactericidal activity against intracellular MTB in the order of gatifloxacin > sitafloxacin > or = levofloxacin. In addition, when test drugs were added at 1/8 C(max) to 1/2 C(max), the efficacy was in the order of sitafloxacin > gatifloxacin > levofloxacin. Thus, it appears that the MIC values of fluoroquinolones are not always predictive of their antimicrobial activity against intracellular MTB. In this context, it was also found that intracellular uptake of these quinolones by MM6-Mphis and A-549 cells was in the order of sitafloxacin > gatifloxacin > levofloxacin. This implies that the cellular permeability of these quinolones is an important factor that determines their efficacy to eliminate intracellular MTB organisms.

Progress in the treatment of aneurysms of the distal aortic arch: approach through median sternotomy.

AIM: A review of past and current operative procedures for the treatment of aneurysms of the distal aortic arch is presented in conjunction with a series of 43 patients. In this study, distal aortic arch aneurysm refers to an aneurysm involving at least the origin of the left subclavian artery, but not extending beyond the left common carotid artery. We excluded dissection aneurysm and extended aneurysm to the descending thoracic aorta from this study. METHODS: Between January, 1985, and March, 2000, 43 consecutive patients (37 males, 6 females; mean age 67.5 years) underwent repair of aneurysms of the distal aortic arch. The approach to the aneurysm was through a left thoracotomy in 4 patients and a median sternotomy in 39 patients, including an additional left thoracotomy continued to a median sternotomy in 2 patients. The supportive methods during surgery were left heart bypass using a centrifugal pump in 4 patients (LHB group), cardiopulmonary bypass with selective cerebral perfusion in 11 patients (SCP group), and cardiopulmonary bypass with continuous retrograde cerebral perfusion in 28 patients (RCP group). In the RCP group, the "aortic no-touch technique" was applied in 21 patients. The operative methods were patch closure in 4 patients, graft replacement of the distal arch using the inclusion technique in 14 patients, and total arch replacement using the exclusion technique in 25 patients. RESULTS: There were 5 hospital deaths: 1 patient in the LHB group, intractable bleeding; 1 patient in the SCP group, rupture of the distal anastomosis; 3 patients in the RCP group, stroke, rupture of the dissection arising from the distal anastomosis, and perioperative myocardial infarction. Stroke occurred in 1 patient (25%) with LHB, 3 patients (27.2%) with SCP, and 1 patient (3.6%) with RCP. Among the postoperative survivors, a new onset of left recurrent nerve palsy occurred in 2 patients (66.7%) with LHB, 1 patient (10%) with SCP, and in 1 patient (4%) with RCP. No neurological injury or left recurrent nerve palsy occurred in the patients who underwent the "aortic no-touch technique". CONCLUSION: Total arch replacement with the graft exclusion technique under profound hypothermic circulatory arrest using RCP through the median sternotomy is a promising surgical treatment for atherosclerotic distal aortic arch aneurysm. The "aortic no-touch technique" further improved the surgical results of the distal aortic arch aneurysm.

[Comparative study of hypothermic circulatory arrest and normothermic distal perfusion for thoracoabdominal aortic aneurysm repair].

BACKGROUND: Hypothermic bypass with circulatory arrest for thoracoabdominal aortic aneurysm (TAAA) repair is employed for its protective effect on spinal cord function and because it avoids clamping the diseased aorta. However, organ dysfunction caused by reperfusion injury as well as bleeding tendencies due to deep hypothermia have been described. In this paper we compared the efficacies of the hypothermic and normothermic operations. METHODS: Between February 1996 and June 2000, 28 patients underwent thoracoabdominal aortic repair. Twenty-three patients were men, 5 were women, and the median age was 55.3 (range 23 to 75 years). Fourteen patients had aortic dissection, and 7 had Marfan syndrome. Fourteen patients required reconstruction of visceral arteries. Twelve patients underwent TAAA repair under deep hypothermic circulatory arrest (H group), and 15 under normothermic distal perfusion (N group), while 1 patient underwent a simple clamp procedure. Perioperative data and early outcomes were compared between groups. RESULTS: The overall 30-day mortality rate was 0%, but 3 patients (25.0%) in II group, and 1 patient (6.3%) in N group died during hospital stay. Operation time and bypass time were longer in H group than N group (operative time 793 min vs. 481 min (p < 0.05): cardiopulmonary bypass (CPB) time 255 min vs. 102 min (p < 0.05). Also, more intraoperative bleeding was found in H group than in N group (3,506 ml vs. 1,220 ml). Spinal cord neurologic deficit did not occur in either group. Respiratory failure occurred in 3 patients (25.0%) in H group and one (6.3%) in N group. Renal failure occurred in 3 (25.0%) in H group, and none in N group. CONCLUSION: Early and mid-term outcome of TAAA repair was almost satisfactory and without neurospiral complications. The deep hypothermic operation is more likely to induce postoperative respiratory and renal dysfunction than the normothermic operation. TAAA repair using deep hypothermic circulatory arrest should be limited to patients with TAAA involving the distal arch or a severely calcified aortic wall.

Effect of different proton pump inhibitors, differences in CYP2C19 genotype and antibiotic resistance on the eradication rate of Helicobacter pylori infection by a 1-week regimen of proton pump inhibitor, amoxicillin and clarithromycin.

AIM: To investigate the effect of different proton pump inhibitors, S-mephenytoin 4'-hydroxylase (CYP2C19) genotype and antibiotic susceptibility on the eradication rate of Helicobacter pylori. METHODS: One hundred and eighty-seven H. pylori-infected peptic ulcer patients were randomly treated with either rabeprazole (10 mg b.d.) or lansoprazole (30 mg b.d.) plus amoxicillin (750 mg b.d.) and clarithromycin (400 mg b.d.) for 1 week. The antibiotic susceptibility and CYP2C19 genotype (extensive or poor metabolizer) were investigated. RESULTS: The eradication rates in the rabeprazole-amoxicillin-clarithromycin (RAC) and lansoprazole-amoxicillin-clarithromycin (LAC) groups were 75% and 69%, respectively, on an intention-to-treat basis, and 80% and 75%, respectively, on a per protocol basis. The eradication rate for clarithromycin-resistant strains was significantly lower than that for clarithromycin-sensitive strains (24% vs. 86%, P < 0.05). For clarithromycin-sensitive strains in the LAC group, there was a tendency for a lower eradication rate in extensive than poor metabolizers. The eradication rate in extensive metabolizers in the RAC group tended to be higher than that in extensive metabolizers in the LAC group (89% vs. 78%, P = 0.079726). CONCLUSIONS: The success of the 1-week proton pump inhibitor-amoxicillin-clarithromycin regimen depends on the susceptibility of H. pylori to clarithromycin. Moreover, differences in CYP2C19 genotype influence the eradication rates of lansoprazole-based therapy, and the rabeprazole-based regimen has an advantage especially in extensive metabolizers.

[Surgical treatment of Marfan syndrome; late results and new strategy].

UNLABELLED: Rapid progress has been made in the treatment of Marfan syndrome. Today, the treatment is relatively established and the results have also improved. Even if surgery is performed, however, vascular lesions may recur late after operation and late prognosis is poor considering the age of patients. Issues such as whether a reoperation should be conducted or how the late results might be improved are subjects of debate. Based on an analysis of recent late data, we have performed operations according to the new treatment policy, and here report the results. A total of 203 consecutive operations were conducted in 141 patients with Marfan syndrome who underwent surgery for aortic aneurysm at our department between February 1973 and August 2001. The mean age of patients was 39 (11 years with a male/female ratio of 95:46. At the first operation, 72 patients were diagnosed with annuloaortic ectasia (AAE), 17 patients with AAE + chronic dissection (DeBakey I), 14 patients with AAE + chronic dissection (DeBakey II), 6 patients with AAE + acute dissection (Stanford A), 11 patients with AAE + dissection (DeBakey III), 9 patients with dissection (DeBakey III) only, 3 patients with AAE + abdominal aortic aneurysm only, and 2 patients with abdominal aortic aneurysm only. The cause of reoperation were a new lesion in 17 patients, dissection in 13 patients and a true aneurysm in 4 patients. In 36 patients, an increase in the remaining lesion occurred or a scheduled stage 2 operation was performed. Reoperation was performed following the Bentall operation in 7 patients, dehiscence of the anastomotic region of the coronary artery in 5 patients, aneurysm of the anastomotic region of the coronary artery in 1 patients, and infection of the artificial valve with aneurysm of the anastomotic region of the coronary artery in 1 patient. Hospital deaths were reported in 8 (6%) patients who underwent composite valve graft replacement (including simultaneous arch replacement) for AAE. Hospital deaths also occurred in 8 (13%) patients who underwent a replacement of the aortic arch, descending thoracic or thoracoabdominal aorta, with no cases of paraplegia reported. In all cases, the replacement was extensive. The observed 10-year survival rate was 70% with a freedom from reoperation of 64%. Although dissection did not reduce the observed survival rate, the 10-year freedom from reoperation was significantly decreased at 49% (p = 0.0007). CONCLUSIONS: (1) Surgery is indicated for AAE when the maximum diameter of the aneurysm prior to onset of dissection is 5 cm. In the case of aortic arch without dissection, the Bentall operation with simultaneous arch replacement should be aggressively performed in order to minimize the future risk of vascular events and to eliminate the need for extensive replacement in a reoperation, a procedure which is associated with a high level of risk. (2) Extensive replacement which is associated with poor results should be avoided where possible and, instead, scheduled staged surgery should be aggressively performed in the early stage when the maximum diameter of the aneurysm in the descending aorta is 5 cm or less. (3) By paying adequate attention to patient education, outpatient follow-up using detailed diagnostic imaging, drug therapy, periodic late surveillance, expedition of scheduled surgery, and to the basic approach as well as endeavoring to improve surgical results by the use of new methods of treatment, it is anticipated that further improvement will be observed in late results.

Profiles of cell-to-cell interaction of Mycobacterium intracellulare-induced immunosuppressive macrophages with target T cells in terms of suppressor signal transmission.

Previously, we have found that immunosuppressive macrophages (M(phi)s) induced by Mycobacterium intracellulare-infection (MI-M(phi)s) required cell contact with target T cells to express their suppressor activity against concanavalin A (Con A)-induced T cell mitogenesis. In this study, we examined the profiles of cell-to-cell interaction of MI-M(phi)s with target T cells. First, MI-M(phi)s displayed suppressor activity in an H-2 allele-unrestricted manner, indicating that MHC molecules are not required for cell contact. The suppressor activity of MI-M(phi)s was reduced markedly by paraformaldehyde fixation or treatment with cytochalasin B or colchicine, indicating that vital membrane functions are required for their suppressor activity. Secondly, the suppressor activity of MI-M(phi)s was independent of cell-to-cell interaction via CD40 ligand/CD40 and M(phi)-derived indoleamine 2,3-dioxygenase, which causes rapid degradation of tryptophan in T cells. Thirdly, precultivation of splenocytes with MI-M(phi)s, allowing cell-to-cell contact, reduced Con A- or anti-CD3 antibody-induced mitogenesis but not phorbol myristate acetate/calcium ionophore A23187-elicited proliferation of T cells. In addition, co-cultivation of T cells with MI-M(phi)s caused marked changes in profiles of the tyrosine phosphorylation of 33 kDa, 34 kDa and 35-kDa proteins and, moreover, the activation of protein kinase C and its translocation to the cell membrane. It thus appears that suppressor signals of MI-M(phi)s, which are transmitted to the target T cells via cell contact, principally cross-talk with the early signalling events before the activation of PKC and/or intracellular calcium mobilization.

Anti-Mycobacterium tuberculosis activities of new fluoroquinolones in combination with other antituberculous drugs.

OBJECTIVES: Studies were undertaken in order to assess the anti- Mycobacterium tuberculosis (MTB) activities of newly developed fluoroquinolones in combination with other antituberculous drugs. METHODS: A new C-8-methoxyl fluoroquinolone, gatifloxacin (GFLX), and a new C-8-chloro fluoroquinolone, sitafloxacin (STFX), in combination with other drugs were examined for their activities against extracellular growing MTB organisms and those replicating in RAW264.7 macrophages (RAW-M phis s). RESULTS: STFX but not GFLX potentiated the activities of rifampin and rifalazil against extracellular MTB. Both GFLX and STFX exhibited combined activities against intramacrophage MTB, when used in combination with rifampin, rifalazil, isoniazid, pyrazinamide, ethambutol, streptomycin, or clofazimine. CONCLUSIONS: Although the observed combined effects varied to some extent from case to case depending on drug combinations, the present findings suggest the usefulness of these new fluoroquinolones in multi-drug regimens for tuberculosis patients.