Interleukin 15 activity in the rectal mucosa of inflammatory bowel disease

Background & Aims: Interleukin (IL)-15 has been found to share many immunoregulatory activities in lymphocytes with IL-2. The aim of this study was to investigate IL-15 activity in organ cultures, localization of IL-15 messenger RNA (mRNA), and proliferation of lamina propria mononuclear cells (LPMCs) in response to recombinant IL-15 using the mucosal tissues obtained from patients with inflammatory bowel disease (IBD). Methods: The contents of IL-15, tumor necrosis factor α, and IL-2 in the culture supernatant of the rectal mucosal tissues were determined by an enzyme-linked immunosorbent assay. Expression of IL-15 mRNA was analyzed by in situ hybridization, and proliferative response of LPMCs to recombinant IL-15 was determined by [³H]thymidine incorporation into DNA. Results: Significantly greater IL-15 activity was detected in active IBD, and this elevation was also observed in inactive ulcerative colitis. In contrast, greater tumor necrosis factor α activity was observed only in active IBD, and IL-2 was not detected in organ cultures. In situ hybridization showed IL-15 mRNA in macrophages and epithelial cells in active IBD specimens, and recombinant IL-15 induced a dose-dependent proliferative response in LPMCs. Conclusions: Mucosal IL-15 may be involved in the pathogenesis of IBD as one of the important mediators in activation of mucosal immune cells.GASTROENTEROLOGY 1998;114:1237-1243     

Inhibition of ciliary activity by phorbol esters in rabbit tracheal epithelial cells

To study the effect of protein kinase C activation on respiratory ciliary activity, we measured ciliary beat frequency (CBF) by a photoelectric technique in response to phorbol esters and cell-permeable diglyceride in cultured tracheal epithelial cells from rabbits. Phorbol 12-myristate 13-acetate (PMA) resulted in a concentration- and time-dependent inhibition of CBF (half maximum inhibitory concentration (IC₅₀)=3×10⁻¹⁰ M) with the maximal decrease being 21.0±1.4% (mean±SE,p<0.001) observed at 10⁻⁶ M. L-α-dioctanoylglycerol (DiC8), another known activator of protein kinase C, likewise reduced CBF in a dose-dependent fashion. In contrast, phorbol 12,13-didecanoate, a non-tumor-promoting phorbol ester that does not stimulate protein kinase C, produced no significant changes in CBF. The decrease in CBF induced by PMA was not affected by blockade of arachidonic acid metabolism with indomethacin and nordihydroguaiaretic acid, but was antagonized by pretreatment with H-7, a specific inhibitor of protein kinase C (p<0.01). Maximal ciliary inhibition with either PMA or DiC8 was not accompanied by a decrease in intracellular concentration of cyclic AMP. These results indicate that activation of protein kinase C has a significant depressive effect on ciliary activity, and hence the airway mucociliary transport function, presumably through a regulatory pathway that is not dependent on cyclic AMP or arachidonic acid metabolites.     

Establishment of a T-Cell Line from Lymphocytes Presumably Implicated in Posttransfusion Graft-versus-Host Disease

Posttransfusion graft-versus-host disease (PTGVHD) is known to develop in immunocompetent patients exhibiting clinical symptoms such as erythroderma, fever, liver dysfunction, diarrhea and pancytopenia. It is speculated that transfused blood donors' lymphocytes might recognize the recipients' HLAs as alloantigens. The thus stimulated lymphocytes might proliferate, expand and finally attack the host's immune system or tissues. However, details regarding these expanded donor cells such as: (1) whether they represent one clone or more, (2) the composition of lymphocyte subsets, and (3) the target HLA antigens of recipients, are not clear, since T-cell lines derived from PTGVHD patients have not yet been obtained. The aim of this study is to characterize T-cells responsible for PTGVHD and to identify their target molecules. For that purpose, we attempted to establish T-cell lines derived from a PTGVHD patient. We show that the established T-cell line, proven to be derived from donor lymphocytes, showed a CD4+ phenotype and had cytotoxic activities. Furthermore, we describe that the target of the cytotoxic T-cell line (CTL) is an HLA-DRBl*0405-related molecule of the patient.     

Specialized transduction of colicin E1 DNA in Escherichia coli K-12.

Genetic studies were made on E. coli K-12 TM96, which carries recombinant molecules constructed by in vitro combination of colicin E1 DNA and a DNA fragment of E. coli for guanine synthesis derived from transducing phage. The recombinant molecules existed as stable plasmids within the cell and contained genes for colicin E1 immunity and the guaA enzyme (xanthosine 5'-monophosphate aminase) together with a part of the lambda genome, R through J: (R-A-F-J)+. A block of the lambda genome, int through Q, was not detected in the recombinant molecule. Thus, this recombinant molecule was named ColEl-coslambda-guaA, and the specialized tranduction of the ColEl-coslambda-guA DNA into various E. coli K-12 cells by lambda phage was described. Lysates prepared by lytic infection of lambda phage onto TM96 or by induction of TM96(lambda) lysogens contained transducing particles which could transduce gua-deleted E. coli to stable guaA+ cells. These transductants were proved to have similar genetic properties as those of TM96. The frequency of transduction was not affected by the presence of an attachement site for lambda, prophage lambda, colicin E1 plasmids, or the recA property within gua-deleted recipient cells. Transducing particles were resistant to EDTA treatment and most of them had an average density of about 1.472. This value corresponds to that of lambda phage particles, which contain about 72% of the lenght of lambda DNA.     

Do eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia?: A preliminary study.

The present study was conducted to examine the effect of eicosapentaenoic acid supplements on pulse wave velocity (PWV) in patients with dyslipidemia as a prospective open-labeled study. Eicosapentaenoic acid supplements (1,800 mg/day) were prescribed to 40 patients, and diet therapy in consultation with a nutritionist was conducted in 44 patients as a control group. These interventions were continued for 12 months, and PWV and blood examinations were performed at the start and end of these interventions. PWV increased in the control group but not in the eicosapentaenoic acid group. After adjustment for age, gender, the initial PWV, and the changes in mean blood pressure during the study period, a general linear model univariate analysis post hoc comparison demonstrated that the change in PWV during the period of study was significantly larger in the control group (42 +/- 20 cm/s) than in the eicosapentaenoic acid group (-9 +/- 19 cm/s) (p<0.05). Thus, this preliminary study suggested that eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia. A further study with a larger number of subjects is proposed to confirm this beneficial effect of eicosapentaenoic acid supplements on arterial stiffness.     

A case of pulmonary Mycobacterium gordonae infection progressed for no therapy]

A 68-year-old woman, who had been healthy until this event, presented with a complaint of productive cough since 2000. She went to a neighboring hospital because of bloody sputum in October 2001. Although chest radiograph showed abnormal findings then, she received only an expectorant and cough remedy. She consulted us complaining of dyspnea on exertion in April 2005. Chest radiograph revealed cavity formation, bronchiectasis and a nodular shadow, and her condition had deteriorated. Microbiologically, acid-fast bacilli were detected three times in the culture of sputum, and Mycobacterium gordonae was identified by the biochemical method. However, this Mycobacterium gordonae could not be identified by the DNA-DNA hybridization method. Our case also probably was considered to be a primary type pulmonary nontuberculous infection because of her clinical course. In addition, we recognized that pulmonary M. gordonae infection also worsens without the therapy.     

Venous tumor thrombosis and cavernous transformation of the portal vein in a patient with gastric carcinoma

A case of extensive extra-and intrahepatic portal tumor thrombosis, with no metastatic foci in liver parenchyma, secondary to advanced gastric carcinoma in a 69-year-old man is reported. The portal tumor thrombosis was characterized by enlargement of the thrombosed segment of the vein, decreased density mass without intraluminal enhancement of the involved vein, nonvisualization of the portal venous branch in the involved lobe, and the so-called cavernous transformation of the portal vein. The surgically resected gastric specimen showed Borrmann type 3 advanced papillary adenocarcinoma. The portal tumor thrombus is presumed to have arisen from vascular invasion in the primary foci of gastric carcinoma, and then to have permeated the portal vein without invasion of liver parenchyma.