Postnatally Induced Inactivation of gp130 in Mice Results in Neurological,Cardiac, Hematopoietic,Immunological, Hepatic,and Pulmonary Defects

The pleiotrophic but overlapping functions of the cytokine family that includes interleukin (IL)-6, IL-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1 are mediated by the cytokine receptor subunit gp130 as the common signal transducer. Although mice lacking individual members of this family display only mild phenotypes, animals lacking gp130 are not viable. To assess the collective role of this cytokine family, we inducibly inactivated gp130 via Cre-loxP–mediated recombination in vivo. Such conditional mutant mice exhibited neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects, demonstrating the widespread importance of gp130-dependent cytokines.     

<Emphasis Type="Italic">Pneumocystis</Emphasis> pneumonia in patients with HIV infection: clinical manifestations,laboratory findings,and radiological features

Pneumocystis pneumonia (PCP) remains the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). Familiarity with the clinical features of PCP is crucial for prompt diagnosis, even if the patient is unaware of their HIV serostatus. We describe herein the clinical features of 34 episodes in 32 patients with AIDS-associated PCP and review the existing literature. As for symptoms, the frequency of fever, cough, and dyspnea was 74%, 74%, and 65%, respectively, and the complete triad was present in only 14 of the 34 episodes on first examination. Median duration from onset of symptoms until diagnosis was 3 weeks, and AIDS-associated PCP tended to take an insidious clinical course. Although laboratory findings were generally nonspecific, measurement of β-D-glucan levels in the serum or plasma was highly useful in the diagnosis of PCP. All but 1 of the patients showed β-D-glucan levels higher than the cutoff value (median, 147 pg/ml; range, 5–6920 pg/ml). Typical radiographic features of PCP are bilateral, symmetrical ground-glass opacities, but a wide variety of radiographic findings were observed. In our patients, high-resolution computed tomography (HRCT) of the lung showed ground-glass opacities sparing the lung periphery (41% of episodes) or displaying a mosaic pattern (29%), or being nearly homogeneous (24%), ground-glass opacities associated with air-space consolidation (21%), associated with cystic formation (21%), associated with linear-reticular opacities (18%), patchily and irregularly distributed (15%), associated with solitary or multiple nodules (9%), and associated with parenchymal cavity lesions (6%).     

Effect of Interleukin-10 on Gut-Derived Sepsis Caused by Pseudomonas aeruginosa in Mice

We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 μg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 μg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1β, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1.0 μg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.     

Cumulative effect of preceding pacing cycle length on ventricular repolarization after a pause

This study was designed to investigate if the components of the QT interval after a pause are influenced by the preceding pacing cycle length. Ten patients (seven women and three men; age 79 +/- 9 years, means +/- SD) with complete atrioventricular block or sick sinus syndrome whose own heart rate was < 40 beats/min were examined. All patients had already undergone implantation of a permanent pacemaker. Ventricular pacing protocol was performed with simultaneous recording of a 12-lead electrocardiogram. One set of regular stimuli for 30 seconds (S1) with a variable cycle length (1,000, 700, and 400 ms) was followed by a single stimulus (S2) with a fixed coupling interval of 1,500 ms. QT intervals in response to the last S1 (S1-QT) and S2 (S2-QT) were measured. The QT interval was divided into two components, the interval from start of Q wave to the peak of T wave (QaT) and that from the peak to end of T wave (Tae). The S2-QT and S1-QT interval shortened in association with a decrease in the S1S1 interval. The abbreviation of S2-QT interval was not associated with a significant change in the Tae interval. The results demonstrated that the QT interval after a pause shortened by reducing the preceding pacing cycle length. This shortening is probably due to a homogenous abbreviation of action potential duration across the ventricular wall.     

In vitro and in vivo antibacterial activities of quinupristin-dalfopristin, a novel injectable streptogramin, against gram-positive cocci and gram-negative respiratory tract pathogens

Quinupristin-dalfopristin, a novel injectable streptogramin, was evaluated for both in vitro and in vivo antibacterial activities in comparison with those of erythromycin, azithromycin, clindamycin, vancomycin, ampicillin, imipenem, and ciprofloxacin. Quinupristin-dalfopristin had high activity against staphylococci and streptococci, including methicillin-resistantStaphylococcus aureus (MRSA), and penicillin-resistantStreptococcus pneumoniae, with MICs at which 90% of strains tested are inhibited (MIC₉₀) equal to 1 μg/mL or less. AgainstEnterococcus spp, quinupristin-dalfopristin was less active than vancomycin with an MIC₉₀ of 32 μg/mL, while againstHaemophilus influenzae, Moraxella (B) catarrhalis andBordetella pertussis, the MIC₉₀s of quinupristin-dalfopristin were 4.0, 1.0, and 0.1 μg/mL, respectively. The minimal bactericidal concentration (MBC) values of quinupristin-dalfopristin against methicillin-susceptible staphylococci, penicillin-resistantS. pneumoniae andH. influenzae were similar to the MIC values, while the MBCs for MRSA andE. faecalis were at least 8-fold greater than the corresponding MIC values. In a murine lung infection model using penicillin-resistantS. pneumoniae, treatment with quinupristin-dalfopristin resulted in a significant reduction in the number of organisms in the lungs compared with that in untreated animals or erythromycin-treated mice (P<0.05). The in vivo efficacy of quinupristin-dalfopristin against experimental septicemia caused by penicillin-sensitiveS. pneumoniae and MRSA was less than that using vancomycin and imipenem-cilastatin, even though it had higher in vitro activity.     

Cyclophosphamide‐induced tolerance in kidney transplantation avoids long‐term immunosuppressive therapy

There has recently been remarkable progress in immunosuppressive agents, such as tacrolimus and cyclosporine. Therefore, the rate of organ establishment has improved in transplantation. However, immunosuppressive agents generally suppress the function of T cells. Thus, opportunistic infections, such as cytomegalovirus infection, are still a major problem in kidney transplantation. Induction of specific tolerance to avoid immunosuppressive drug therapy after kidney transplantation is considered as the ultimate goal of transplantation. Various factors induce tolerance that involves establishment of hematopoietic chimerism and various cell subsets. In particular, we have carried out various studies regarding the cyclophosphamide‐induced tolerance system. Tolerance is induced after establishment of hematopoietic chimerism after donor bone marrow transplantation. At the clinical stage, kidney transplantation before administration of cyclophosphamide after transfusion of bone marrow to create hematopoietic chimera is considered to be one of the most successful protocols. Furthermore, recent studies have shown the involvement of multiple populations of immune cells in preserving immunological tolerance and promoting long‐term renal grafts. The present review focuses on how cyclophosphamide and other immune factors induce tolerance in kidney transplantation.     

Innovative technology for tissue disruption by explosive-induced shock waves

We have developed a novel, less invasive, shock wave source that can be introduced into an arbitrary position in a human body percutaneously. Using this technique we can disrupt cells locally. The shock wave source consists of an explosive, an optical fiber, a balloon catheter, and a Nd:YAG laser, which generates a spherical explosive shock wave. The destructive potential of the present source for injuring tissue was confirmed and the subsequent cell elongation and split in the direction of the shock wave has been observed.