Cimetidine and placebo-cimetidine in the treatment of patients with chronic gastric ulcer (a multiclinical randomized double-blind comparative study)

The efficacy of a 4-week cimetidine treatment was examined by a double-blind randomized study in 37 outpatients with endoscopically verified chronic gastric ulcer. The patients received a daily dose of 3 times 1 tablet and, at night before going to bed 2 more tablet, thus a total amount of 1 g cimetidine, or cimetidine-placebo, but in case of complaints they could take in addition a mixed alkaline powder. Patients not recovering in response to a 4-week treatment, were then administered daily 5 tablets of cimetidine up to their complete recovery. Endoscopic, laboratory and clinical examinations were carried out every other week. As a result of a 4-week treatment, 56% of the cimetidine group recovered. The difference was not significant (P less than 0.2). The size of the ulcer and the intensity of the complaints were reduced significantly in both groups. The decrease in the size of the ulcer was significantly greater in the first two weeks of cimetidine treatment than in the cimetidine-placebo group (P less than 0.05). This favourable dynamics of ulcer healing was not felt in the second two weeks of treatment, and after four weeks there was no difference in the size of the residual ulcer to between the two groups. Cimetidine seemed to be a suitable drug for treating chronic gastric ulcer, since its healing rate proved to be better than that of placebo, the gain in weight also was favourable and there were no side-effects.     

Role of the YadA protein in prevention of opsonization of Yersinia enterocolitica by C3b molecules.

When mixed with normal human serum, wild-type pathogenic Yersinia enterocolitica, previously incubated at 37 degrees C, fixed less C3b than its variant cured of the virulence plasmid pYV. Mutants unable to secrete the Yop proteins were still protected against C3b deposition. By contrast, mutants deficient in the production of outer membrane protein YadA fixed more C3b than their YadA+ parent. Gene yadA, cloned as a minimal polymerase chain reaction fragment and introduced in trans, complemented the mutations. Production of YadA by recombinant Escherichia coli LK111 also resulted in a reduction of the amount of C3b deposited on the bacterial surface. The reduction of C3b at the surface of Y. enterocolitica YadA+ compared with YadA- cells correlated with an increase of the amount of factor H fixed at the bacterial surface. The YadA monomer separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane was able to bind factor H. We conclude that factor H bound to YadA reduces the C3b deposition on the bacterial surface, probably by a rapid inactivation of C3b.     

Aberrant interleukin (IL)-4 and IL-5 production in vitro by CD4+ helper T cells from atopic subjects.

The cytokine secretion profiles of T cell lines (TCL) specific for purified protein derivative (PPD) or streptokinase (SK), contemporarily derived from nine atopic and nine nonatopic individuals, were compared. Upon stimulation with phorbol myristate acetate (PMA) plus anti-CD3 monoclonal antibody (mAb), all TCL from both atopics and nonatopics produced interleukin (IL)-2 and interferon (IFN)-gamma. The mean IL-2 production by PPD- or SK-specific TCL from both atopics and nonatopics was similar, whereas the mean IFN-gamma production by TCL derived from atopics was significantly lower. In addition, both PPD- and SK-specific TCL from atopics produced detectable amounts of IL-4 and IL-5, whereas the corresponding TCL derived from nonatopics did not. A total number of 107 and 99 PPD-specific CD4+ T cell clones (TCC) were then derived from TCL of 4 atopic and 4 nonatopic donors and assessed for their profile of cytokine production in response to stimulation with either PMA plus anti-CD3 mAb or the specific antigen. Under both these experimental conditions, virtually all PPD-specific TCC from both atopic and nonatopic individuals produced IL-2 and IFN-gamma. In contrast, the great majority of PPD-specific TCC derived from nonatopic individuals did not produce IL-4 and IL-5, whereas high proportions of PPD-specific TCC derived from atopic donors displayed the ability to produce noticeable amounts of IL-4 and IL-5 besides IL-2 and IFN-gamma. These data indicate that CD4+ T cells from atopic individuals are able to produce IL-4 and IL-5 in response to bacterial antigens, such as PPD and SK, that usually evoke responses with a restricted type-1 T helper (Th1)-like cytokine profile in nonatopic individuals. Aberrant IL-4 production by Th cells may represent one of the immune alterations responsible for enhanced IgE antibody production in atopic people.     

Antiinflammatory-antioxidant treatment with a methane sulfonanilide in allergen-induced asthma.

Two groups of six asthmatic patients with biphasic bronchospastic response to inhaled Dermatophagoides pteronyssinus allergen extract were studied in a double-blind fashion. Early and late asthmatic reactions to allergen inhalation challenge were determined before and at the end of a 2-week treatment period with nimesulide (100 mg bid orally), a sulfonanilide with antioxidant properties, or placebo. Bronchial responsiveness to methacholine was evaluated 24 hours before and after allergen inhalation challenges. The dose of allergen causing EAR (15% decrease in FEV1) and the severity of LAR (maximum FEV1 fall) were similar before and at the end of the treatment period in both groups. In patients treated with nimesulide, bronchial responsiveness to methacholine was significantly increased after allergen inhalation challenge both before and at the end of the treatment period. These results do not support the hypothesis that the production of oxygen-free radicals plays a significant role in the development of bronchial hyperresponsiveness and late phase reaction to allergen in asthma.     

Quantitative and qualitative differences in HLA-DR molecules correlated with antigen-presentation capacity

The monoclonal antibodies 7.3.19.1 (anti-DRw52-like) and B8.11.2 (anti-DR framework) were used for the isolation and characterization of HLA class II molecules expressed by HLA-DR3 and DR5 homozygous B cell lines. Sequential immunoprecipitation studies demonstrated that from these cells class II molecules can be isolated which are characterized by the presence or absence of DR framework (DR) and DRw52-like (DRw62) determinants: (DR+, DRw52+), (DR+, DRw52-) and (DR-, DRw52+). The DR3 donor cells appeared to express only the (DR+, DRw52+) and (DR-, DRw52+) class II molecules whereas DR5-positive cells express only the (DR+, DRw52+) and (DR+, DRw52-) class II molecules. Besides qualitative differences some of the above-mentioned molecules appeared to differ in their levels of expression. To investigate whether this might have functional implications, cells with the HLA-DR3 and -5 haplotypes were used to present antigen purified protein derivative of tuberculin (PPD) to PPD-specific T cell lines and the blocking capacity of the two monoclonal antibodies 7.3.19.1 and B8.11.2 was determined. A remarkable correlation was observed between the type of class II molecule blocked by these monoclonal antibodies and its quantitative expression. However, (DR-, DRw52+) molecules, clearly expressed by DR3 cells, were not involved in the presentation of PPD. This indicates that not only quantitative but also qualitative aspects may play a role in the selection of the type of class II molecule that will be involved in antigen presentation.     

Interferon in experimental viral infections in mice: tissue interferon levels resulting from the virus infection and from exogenous interferon therapy.

In mice given single intraperitoneal doses of interferon, serum interferon levels peaked at 1 h postinjection and were reduced to zero at about 8 h. The interferon concentrations in spleen, liver, and lungs were about 100-fold higher than could be expected from the amount of serum contained in these organs. In the brain only low levels of antiviral activity were detected. In mice infected intraperitoneally with Mengo virus, viral replication in the brain occurred around day 4 and was accompanied by the appearance of large amounts of interferon (approximately 10(3.25) U/g). This was preceded, however, by viral replication in the spleen and by the appearance of modest amounts of interferon in spleen and serum. In these mice protection could be obtained with relatively small doses of interferon, provided protection could be obtained with relatively small doses of interferon, provided they were given before the time of maximal levels of endogenous serum interferon. In mice infected intranasally with vesicular stomatitis virus, virus replication in the brain started within 24 to 48 h and increased with time; also, small amounts of interferon (10(2) to 10(2.5) U/g) were already detectable on days 1 and 2. The major peak of virus replication in the brain occurred on days 5 to 6 and was accompanied by the appearance of large amounts of interferon (approximately 10(3.25) U/g). In this model early treatment with interferon also provided protection, but only if given in larger doses than in the Mengo virus system. Athymic (nu/nu) mice developed a chronic systemic infection when inoculated with a demotropic strain of vaccinia virus. No interferon was detected in sera, livers, spleens, or lungs of these animals; some mice had low levels of interferon-like antiviral activity in the brain, but no attempt was made to characterize this material. Daily administration of large doses of interferon failed to exert an effect on the development of this chronic disease. Yet, normal (NMRI) mice were protected against acute infection with dermotropic or neurotropic strains of vaccinia virus, and athymic mice were partially protected against acute lethal infection with neurotropic vaccinia virus.     

Fertilization, pregnancy and embryo implantation rates after ICSI with fresh or frozen-thawed testicular spermatozoa

This study aimed to determine whether fertilization and implantation rates after intracytoplasmic sperm injection (ICSI) with fresh or frozen-thawed testicular spermatozoa were comparable. Between 1 January 1996 and 31 December 1996, 65 ICSI cycles with testicular spermatozoa and 35 cycles with frozen-thawed testicular spermatozoa were carried out. In 50 out of 65 ICSI cycles, testicular spermatozoa could be retrieved and in 34 out of 35 cycles carried out with frozen-thawed testicular spermatozoa, motile spermatozoa could be recovered. The fertilization rate after ICSI with frozen-thawed testicular spermatozoa was significantly lower (71.1%; P < or = 0.008) than with fresh testicular spermatozoa (79.3%). The pregnancy rate was similar for both groups (38.2 and 26.5 %). The implantation rate per transferred embryo, however, was significantly lower in the frozen-thawed rather than in the fresh testicular sperm group (9.1 versus 24.6%; P = 0.001). The live birth rate per transferred embryo was also higher in the group in which fresh testicular spermatozoa were used (18.8 versus 7.9% P = 0.043). This retrospective study shows that is possible to achieve a high fertilization rate after ICSI with both fresh and frozen-thawed testicular spermatozoa but implantation and live birth rates per transferred embryo, however, are significantly lower after ICSI with frozen-thawed than with fresh testicular spermatozoa.      

Classification of B-cells according to their differentiation status, their micro-anatomical localisation and their developmental lineage

B-lymphocytes or B-cells form a diverse and flexible repertoire of immune cells that are reactive to almost all potential pathogens by means of the production of antigen-specific immunoglobulins. They can be divided into different populations or subsets, characterised by a distinct combination of properties. These subsets are identified on the base of their differentiation status (precursor B-cells, peripheral B-cells), their localisation in the micro-anatomical compartments of the B-cell follicle (marginal zone B-cells, lymphocytic corona B-cells, follicle centre B-cells), and the developmental lineage to which they belong (B-1 cells, and B-2 or conventional B-cells). The latter classification of B-cells into B-1 cells and B-2 cells is commonly followed by immunologists, mainly in the study of mice models, while pathologists and haematologists tend to use a terminology for B-cells which refers to their localisation in the micro-anatomical compartments of the B-cell follicle and/or differentiation status. In this review, we will discuss the various subsets of B-cells and point to the similarities between the various classification systems in use.