Auto-MHC class II-reactive T cell line obtained from MRL/+ mice suffering from lpr-GVHD. II. Analyses of functional characteristics of T cell line by in vivo administration.

Functional characteristics of an autoreactive (I-Ek-restricted) T cell line (l/+ T1), previously established from MRL/M(p-)+/+(MRL/+) mice with lpr-GVHD, were analyzed in vivo. Intravenous injection of l/+ T1 cells to non-irradiated H-2k (MRL/+ or AKR) mice (but not H-2d mice) induced enhanced spontaneous proliferation of recipient spleen cells; this was also I-Ek self-restricted. This augmented self-reactivity seemed to be mediated by recipient L3T4+ T cells, since few l/+ T1 cells were detected in the spleen cells of l/+ T1-injected AKR mice by cell surface marker analyses, and the treatment of the spleen cells with anti-Thy-1.1 antibody (Ab) or anti-L3T4 Ab plus complement abolished this enhanced spontaneous proliferation. The production of IgM rheumatoid factor (RF) in AKR mice and IgG RF in MRL/+ mice increased, although no enhancement of anti-ssDNA Ab production was observed. Judging from both spleen B cell proportion and serum Ig levels, autoantibody induction by the injection of l/+ T1 cells was not associated with polyclonal B cell activation. When lethally irradiated B10 congenic mice were used as recipients, B10. BR mice showed elevated levels of IgM anti-ssDNA and IgM RF 1 wk after l/+ T1 cell injection; it is likely that lethal irradiation causes autoantigens, particularly DNA, to be exposed. These findings suggest that the autoreactivity of l/+ T1 cells can be transferred to recipient L3T4+ T cells via T-T interaction or the immunological network, and that increased autoreactivity induces autoantibody production in the presence of autoantigen stimulation. In contrast to the stimulatory effects observed in AKR and MRL/+ mice, MRL/Mp-lpr/lpr(MRL/lpr) mice showed a different response to the injection of l/+ T1 cells; spontaneous proliferation of spleen cells and autoantibody production were not enhanced, and suppression of the mitogen responses was observed. It is discussed that lpr-GVHD may be due to these unusual features of MRL/lpr mice.     

Branchial cleft cysts. Histologic and immunohistochemical aspects

8 cases of branchial cleft cysts and 1 case of branchiogenic carcinoma were examined immunohistochemically for detectable keratin, immunoglobulins (IgG, IgA, IgM), carcinoembryonic antigen (CEA), factor VIII related antigen (Factor VIII RGA), and lysozyme. Lectin binding patterns were also determined. Histologically, cystic lining epithelia were classified into stratified squamous epithelium without keratinization, columnar epithelium with or without cilia, or a mixture of both. Almost all of the cases indicated accompanying lymphoid structures with germinal centers. Keratin expression in epithelial cells was slightly positive, and lectin binding affinities in them were similar to those of oral squamous epithelium. CEA was found on the surface border of columnar epithelial cells, but cystic epithelia in most of the cases were devoid of lysozyme. Endothelial cells of capillary vessels showed positive binding by UEA-1 lectin and the presence of factor VIII RAG. In the lymphoid structures, there were scattered strongly positive lysozyme-staining cells as well as a few lymphocytes bearing IgG, IgA, or IgM.     

Development of a non-invasive treatment system for urinary incontinence using a functional continuous magnetic stimulator (FCMS)

A system composed of a functional continuous magnetic stimulator (FCMS) and a saddle-type coil has been developed for non-invasive treatment of urinary incontinence, especially stress incontinence and urge incontinence. The FCMS conditions were as follows: 2 kW maximum electrical power consumption, 800 V maximum capacitor voltage, 720 μs pulsewidth (180 μs rise time), and 5–30 Hz frequency. A frequency between 5 and 10 Hz is used to treat urge incontinence and a frequency between 25 Hz and 30 Hz is used to treat urge incontinence. The coil (120 mm long, 90 mm wide and 50 mm thick) fits the most suitable region for this treatment, the region from the anus to the perineum. The coil is cooled to maintain a coil temperature between 20 and 25°C so that it can be used efficiently and safely. In experiments with anaesthetised dogs, it was confirmed that the urethral pressure increased when the circumference of the perineum received continuous magnetic stimulation of 720 μs pulsewidth (180 μs rise time), 10Hz frequency and about 520 V capacitor voltage. This result suggests that magnetic stimulation can be effective as a urinary incontinence therapy.     

Antibacterial property and clinical effect of gatifloxacin,a novel quinolone antibacterial agent

Gatifloxacin, a novel 8-methoxyquinolone, was approved in April 2002 and launched in June 2002. Gatifloxacin shows a broad spectrum of antibacterial activity against Gram-negative, Gram-positive, anaerobic, and atypical pathogens. The activity is higher than those of other quinolones against RTI pathogens of S. pneumoniae including the penicillin-resistant strains, H. influenzae, Mycoplasma, and Chlamydia. This drug strongly inhibits the type II topoisomerase, DNA gyrase, and topoisomerase IV of S. pneumoniae and S. aureus to nearly the same extent, leading to the potent activity and low resistance. After an oral administration in humans, gatifloxacin is well absorbed and distributed, and the majority is excreted in the urine as the unchanged form. Its serum half-life is 7-8 h. The clinical effectiveness was observed for various infectious diseases including RTI and UTI. The bacterial eradication rate is 94.1% for Gram-positives, 90.7% for Gram-negatives, and 97.7% for anaerobes. In particular, gatifloxacin showed a high eradication rate of 98.7% for S. pneumoniae. The total cure rate and eradication rate of gatifloxacin in clinical studies are 91.1% and 93.3%, respectively, indicating that the potent activity and good PK profile account for its clinical efficacy.     

Effect of psychiatric group intervention on natural-killer cell activity and pregnancy rate

We investigated the effects of psychiatric group intervention on the emotions, natural-killer (NK) cell activity and pregnancy rate in Japanese infertile women by a randomized study. Thirty-seven women completed a 5-session intervention program and were compared with 37 controls. Psychological discomfort and NK-cell activity (47.7% to 34.1%, P<.0001) significantly decreased after the intervention, whereas no significant changes were observed in controls. According to a 1-year follow-up of both groups, the pregnancy rate in the intervention group was significantly higher than that of controls (37.8% vs. 13.5%, P=.03). Psychological group intervention was therefore effective in Japanese infertile women.     

Voxel-based comparison of regional cerebral glucose metabolism between PSP and corticobasal degeneration

OBJECTIVES: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative disorders that may be accompanied by dementia and parkinsonism as clinical symptoms. The purpose of this study was to elucidate cerebral metabolic differences of these two diseases with cognitive impairments by [18F] fluorodeoxyglucose (FDG) and positron emission tomography (PET). METHODS: A total of 12 patients with PSP (age: 62.8+/-6.0 years old, m: 7, f: 5, Mini-Mental State Examination (MMSE): 23.4+/-2.6), 12 patients with CBD (age: 64.8+/-6.3 years old, m: 6, f: 6, MMSE: 22.9+/-4.5), and age-matched healthy subjects (normal control (NC)) (age: 63.8+/-7.7 years old, m: 7, f: 5) were subjected to FDG-PET to obtain glucose metabolic images. We compared regional cerebral metabolic images by a voxel-by-voxel analysis with statistical parametric mapping (SPM) among PSP, CBD, and NC subjects, and evaluated differences of hypometabolic regions. RESULTS: The patients with PSP showed reduced cerebral glucose metabolism in the medial and lateral frontal gyri, basal ganglia, and midbrain compared with NC, whereas the patients with CBD showed significant reduction in the parietal lobes (p<0.001). SPM also revealed parietal hypometabolism in CBD patients compared with PSP patients (p<0.001). CONCLUSIONS: The predominant parietal glucose metabolic reduction in CBD patients was different from previously reported findings. This finding would be the characteristic substance of patients with CBD accompanying cognitive impairments. Our findings suggest that measurement of glucose metabolism by PET and a voxel-based analysis is useful to understand the pathophysiology of these two diseases with cognitive impairments.     

Secondary transplantation following a period of isografting: experimental study in rats

The authors describe a study in which groin flaps from 20 Wistar rats were transplanted to another group of 20 Wistar rats and, after various time intervals, the groin flaps were re-transplanted back to the original animals. The goal of the first transfers was to preserve the flap in the second group of animals (isopreservation). During the isopreservation period, the second rat (the preserver) was treated with steroids or FK506 for immunosuppression. Thirty-three free groin flap transfers were performed between 40 rats. If possible, the same flap was transferred twice between two animals, one as an isograft, and other as an autograft following an isopreservation period in 13 pairs of animals. (A second transfer was not possible in seven pairs of animals.) The period for isopreservation varied between 2 days and 1 week. The survival of the flap was observed by visual inspection, laser Doppler flowmeter measurements, and was correlated with serial histopathologic examinations of skin and vessel biopsy specimens, including the anastomosis site. The severity of histopathologic signs that might be related to developing rejection was increased by the preservation time, and was more noticeable after the second transfer. The authors showed that successful secondary transplantation of the rat groin flap with a 1-week follow-up could be achieved, following isopreservation of at least up to 5 days.     

Helicobacter pylori may survive ampicillin treatment in the remnant stomach

Helicobacter pylori (H. pylori) is a Gram-negative curved rod-like or spiral bacterium that chronically infects the human gastric mucosa, and is a major risk factor for gastritis, gastric and duodenal ulcer and adenocarcinoma of the stomach. After partial gastrectomy, some patients may have persistent H. pylori infection for five years or more. In this study, we detected three bacteria, i.e., Klebsiella pneumoniae, Enterobacter aerogenes, and Escherichia coli, in the gastric juice of patients with a remnant stomach. Some of these bacteria produced beta-lactamase. These findings are potentially important since such bacteria could provide H. pylori with the chance to acquire drug resistance and to transfer drug resistance genes. This could be one reason why H. pylori is difficult to eradicate in the remnant stomach.