Intraepithelial lymphocytes in colon have similar properties to intraepithelial lymphocytes in small intestine and hepatic intermediate TCR cells

Recently, properties of intraepithelial lymphocytes (IEL) in the colon (C-IEL) have been analyzed in comparison with those of IEL in the small intestine (SI-IEL). We compared the properties of C-IEL with those of SI-IEL and hepatic intermediate TCR cells, two other types of extrathymic T cells. C-IEL and intermediate TCR cells contain many NK1⁺T cells, although SI-IEL contain few. V and V usage of C-IEL was the same as that of SI-IEL, and that of intermediate TCR cells was different. C-IEL responded to Con A while SI-IEL did not. As to adhesion molecules, C-IEL include both extrathymic and thymus-originated type T cells. With age, TCR-⁺CD4⁺CD8⁺ cells do not increase among C-IEL but do increase among SI-IEL. IL-2R⁺ or CD4^–CD8^– C-IEL increase as observed in the liver. These results indicate that these organ-specific T cells have different roles at their respective sites and that they may be of different lineages.     

Adhesion molecule expression on peripheral blood mononuclear cells in rheumatoid arthritis: Positive correlation between the proportion of L-selectin and disease activity

Summary The expression of a series of adhesion molecules (the integrin family, the immunoglobulin superfamily, CD44 and the selection family) on peripheral blood mononuclear cells (PBMC) from RA patients was investigated by flow-cytometry. L-Selectin (CD62L) in the selectin family was more significantly expressed on PBMC from RA patients as compared to those from normal controls. Further, RA patients exhibited a slight but significant increase of VLA-2 (CDw49b), p150,95 (CD11c), and VNR- (CD61) in the integrin family. The enhanced expression of L-selectin was positively correlated with disease activity.An increase in the proportion of L-selectin⁺CD4⁺ cells in PBMC from patients with RA and its clinical significance is reported.     

Successful treatment by voliconazole for pulmonary and adductor magnus muscle aspergillosis induced by immunosuppressive therapy for hypersensitivity pneumonia]

A 74-year-old woman was treated with steroid and cyclosporine A for hypersensitivity pneumonia. To examine the causes of general fatigue and increased levels of beta-D glucan in serum, she was admitted to our hospital. Chest computed tomography (CT) scan revealed nodular opacity with a well-defined margin in the right S1. 67Ga scintigraphy image showed high uptake in the left thigh and CT showed circularly enhanced lesions in the thigh. An ultrasonography-guided needle aspiration and biopsy of the muscle abscess allowed isolation of Aspergillus fumigatus and evidence of necrotic tissues around the granuloma formation. We therefore diagnosed invasive aspergillosis. Because of the poor response to initial therapy with micafungin and itraconazole for 4 weeks, we treated her with voliconazole (VCZ). Spectacular regression of lung lesions and muscle abscesses was rapidly achieved. Furthermore, the high level of beta-D glucan in serum decreased gradually. This case suggests that administration of VCZ can be recommended for deep seated mycoses.     

Effect of post-exposure prophylaxis with oseltamivir for those in contacts with influenza patients in pediatric wards

During the influenza season, outbreaks of influenza may occur in the pediatric wards due to spread from the patients hospitalized with influenza, or from those hospitalized during the latency period and develop influenza afterwards. Post-exposure prophylaxis with neuraminidase inhibitors has been reported to be effective in preventing outbreaks among household members and nursing home residents. However, for nosocomial spread, its effectiveness and possible adverse effects are to be determined. During the 2002/2003 influenza season, we experienced a total of 3 nosocomial outbreaks of influenza in the pediatric wards in two hospitals in the Kanto district, Japan. Since the number of contacts who developed influenza had been increasing despite the isolation precaution implemented, post-exposure prophylaxis with oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, once a day for 7-10 days) was implemented with a permission from the parents to terminate the outbreaks. In the outbreaks (one with influenza A, two with influenza B), a total of 29 inpatients had contact with influenza patients: among those 29, 13 were given post-exposure prophylaxis, 16 were not. Out of 16 patients who did not receive post-exposure prophylaxis, 11 (69%) developed influenza: out of 13 with post-exposure prophylaxis, none developed influenza. Those patients who developed influenza were given oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, twice a day for 5 days) and accommodated in a private room or a room with other patients with influenza of the same type. No significant adverse effects due to oseltamivir were observed among those who were enrolled in this study.     

Distribution, plasma concentration, and in vivo prolactin-releasing activity of peptide histidine methionine in humans

The distribution of immunoreactive peptide histidine methionine (PHM) in human tissues and its plasma concentrations were examined using a specific RIA and gel filtration chromatography. The effects of synthetic PHM on anterior pituitary hormone secretion also were studied. Immunoreactive PHM was found in all tissues studied; high concentrations were found in the gastrointestinal tract, lung, and parotid gland. Subsequent but smaller amounts of PHM were found in the hypothalamus, pituitary stalk, olfactory lobe, and cerebral cortex. The distribution of immunoreactive PHM in human tissues was very similar to that of vasoactive intestinal polypeptide (VIP), and PHM and VIP were in equimolar concentrations. Immunoreactive PHM was also detectable in plasma of normal subjects, and similar plasma concentrations were found in patients with prolactinomas. Molecular sieve chromatography of extracts of nonneural tissues and plasma extracts revealed only one peak, eluting in the position of synthetic PHM. Two peaks of immunoreactive PHM were found in brain tissue; one coeluted with synthetic PHM, and the other eluted in the high mol wt region. Bolus injections of synthetic PHM significantly increased plasma PRL levels in a dose-dependent manner. However, PHM did not alter plasma GH, TSH, ACTH, LH, or FSH levels. These results indicate that PHM is distributed widely in human tissues, and posttranslational processing of the VIP-PHM precursor molecule may be different in different tissues. The finding of equimolar distributions of PHM and VIP is consistent with the notion that these two peptides are synthesized from a common precursor. The presence of immunoreactive PHM in human hypothalamic and pituitary stalk tissue and its specific in vivo PRL-releasing activity suggest that PHM may play an important role in the regulation of PRL secretion.     

Fusobacterium varium localized in the colonic mucosa of patients with ulcerative colitis stimulates species-specific antibody

BACKGROUND: Microbial agents are a possible cause of ulcerative colitis. We have previously reported evidence of bacteria invading the colonic mucosa of patients with ulcerative colitis. We have isolated bacteria from inflamed colonic mucosa, examined the localization of the species in the mucosa, and assayed for serum antibodies to the bacteria. METHODS: Cohorts of 31 per group were enrolled from patients with active ulcerative colitis, Crohn's disease, ischemic colitis, and colon adenomas. A group of 31 healthy controls were also studied. The presence of bacteria in biopsies of patients with ulcerative colitis was analyzed by both isolation and immunohistochemistry. Sera from patients were tested for bacterial antibodies using both Western blots and enzyme-linked immunosorbent assay (ELISA). RESULTS: Only sera from patients with ulcerative colitis gave specific reactions with Fusobacterium varium in Western blot assays. The detection rate of specific bands was higher for patients with ulcerative colitis (61%) than for subjects with either Crohn's disease (13%) or healthy controls (29%) (P < 0.001 and P = 0.021, respectively). The ELISA showed that the mean optical densities with extracts of F. varium as antigen were significantly higher for ulcerative colitis patients than for subjects with either Crohn's disease or healthy controls (P < 0.001). Immunohistochemical detection of F. varium in colonic mucosa was significantly higher in patients with ulcerative colitis (84%) than for subjects with either Crohn's disease (16%) or other controls (3-13%) (P < 0.001). CONCLUSIONS: Fusobacterium varium bacteria were present in a significant number of patients with active ulcerative colitis, and should be tested in therapeutic trials in order to confirm the causal relationship between F. varium and ulcerative colitis.     

Prothrombin levels in newborn infants by the carinactivase-1 method

A recently developed method to quantitate prothrombin in plasma uses the carinactivase-1 (CA-1) method. The present study was designed to establish the reference value by the CA-1 method in the neonatal period and to explore the effect of gestational age, birth weight, concurrent diseases, and vitamin K administration on the prothrombin levels. We enrolled 78 consecutive neonates. The gestational ages ranged from 28 to 41 weeks, and the birth weight ranged from 850 to 3750 g. Twenty-nine infants had concurrent diseases, and the others (n = 49) were healthy. A 300 microL blood sample was drawn into a plastic syringe containing 60 U freeze-dried buffered heparin. Prothrombin levels did not differ between appropriate-for-date (AFD) and light-for-date (LFD) babies (p = 0.090) or between groups with and without concurrent diseases (p = 0.210). In healthy AFD babies, prothrombin levels correlated with gestational age (r = 0.465, p = 0.003) and birth weight (r = 0.458, p = 0.003). In healthy low-birth-weight infants (n = 14) and those with concurrent diseases (n = 17), the changes after vitamin K administration were not significant. The CA-1 method is of clinical use in monitoring coagulation during the early neonatal period.     

Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid

A 32-year-old woman with relapsed Philadelphia chromosome-positive acute lymphoblastic leukaemia was treated with imatinib mesylate (formerly STI571), a selective inhibitor of BCR/ABL tyrosine kinase. Although the initial marrow response was good and stably maintained, she subsequently relapsed with extensive infiltration of leukaemic cells into the central nervous system (CNS). After controlling her CNS disease with additional intrathecal chemotherapy, we measured the concentration of imatinib in cerebrospinal fluid (CSF) and blood simultaneously. The concentration of imatinib in CSF was about 92-fold lower than that in blood. These results suggest that imatinib poorly penetrates the blood-brain barrier and has limited activity against CNS leukaemia.