Leukocytapheresis (LCAP), performed with a leukocyte removal filter, was administered five times, at 1-week intervals, for 5 weeks of intensive therapy and five times, at approximately 1-month intervals, for approximately 5 months of maintenance therapy, to 13 patients with inflammatory bowel disease (IBD) diagnosed as ulcerative colitis (UC) in 8 and Crohn's disease (CD) in 5. Clinical and blood examinations showed no side effects in any of the patients. During the intensive therapy, excellent or moderate clinical response was recognized in 11 of the 13 patients (84.6%), of whom 6 had a dramatic response; the excellent or moderate clinical response continued throughout the maintenance therapy in 8 of the patients (61.5%). Flow cytometry showed that the patients who had improved generally had high values for percentages of HLADR+, HLADR+CD3+, and HLADR+CD8+ cells before the first LCAP, and that these values and the C-reactive protein levels and erythrocyte sedimentation rates had decreased to the normal range by the end of both intensive and maintenance therapy. In the patients who showed poor response, in contrast, all the above values had been at or near normal before the initial LCAP administration. The clinical improvement in the absence of any additional medical treatment suggests that LCAP has the capacity to influence the causal mechanism(s) of IBD and that IBD is strongly associated with the cell-mediated immune response.

BackgroundEating is one of the most important daily activities in managing patients with dementia. Although various eating disturbance occur as dementia progresses, to our knowledge, most of the studies focused on a part of eating disturbance such as swallowing and appetite. There have been few comprehensive studies including eating habits and food preference in patients with Alzheimer’s disease (AD). The aims of this study were to investigate almost all eating disturbance and to examine the relationship of eating disturbance to dementia stage in AD.MethodsA total of 220 patients with AD and 30 normal elderly (NE) subjects were recruited. Eating disturbance was assessed by a comprehensive questionnaire that had been previously validated. Potential relationships between the characteristics of eating disturbance and dementia stage as classified by the Clinical Dementia Rating (CDR) were assessed.ResultsOverall, 81.4% of patients with AD showed some eating and swallowing disturbance, whereas only 26.7% of the NE subjects had such a disturbance. Even in an early stage, patients with AD had many types of eating disturbance; “Appetite change” was shown in nearly half of the mild AD patients (49.5%). In the moderate stage, the scores of “change of eating habits and food preference” were highest, and in the severe stage “swallowing disturbance” became critical.ConclusionIn AD, the relationship of dementia stage to eating disturbance differs according to the type of eating disturbance. The relationships between various eating disturbance and the severity of dementia should be considered.

Leukocytapheresis (LCAP) with a leukocyte removal filter column was administered for 45 patients with ulcerative colitis (UC). We evaluated changes in the leukocyte count and the differential percentages during LCAP. Cytokine production was assessed from each patient's peripheral mononuclear cells or monocytes. Flow cytometry was performed to assess the removal rates of activated cells and adhesion molecule positive cells by LCAP. Clinical improvement was recognized in 35 of 45 patients during intensive LCAP therapy, and it continued throughout maintenance therapy in 32 patients (71.1%). The leukocyte count was decreased to about 40% during the first 30 min, but it increased to approximately 170% at 20 min after the completion of LCAP. The concentration of tumor necrosis factor (TNF)alpha before LCAP in the effective group was higher than it was in either the ineffective group or the control group. Its level decreased to near normal range after LCAP. In the effective group, the concentrations of interleukin (IL)-1beta, IL-2, interferon (IFN)gamma, and IL-8 were near the normal upper limits before LCAP; however, they had decreased after LCAP. The concentration of IL-4 increased after LCAP. In the ineffective group, in contrast, the concentrations had been at or near normal before the initial LCAP treatment. Flow cytometry study revealed that LCAP could remove the activated cells and adhesion molecule positive cells more effectively. The clinical improvement and the changes observed before and after LCAP therapy suggest that LCAP is able to intervene in the causal mechanism(s) of UC.

SummaryIn order to clarify the potential role of von Willebrand factor (vWf) in attenuating the inactivation of factor VIII (fVIII) by those antibodies with C2 domain specificity, we investigated a panel of 14 human antibodies to fVIII. Immunoblotting analysis localized light chain (C2 domain) epitopes for four cases, heavy chain (A2 domain) epitopes in five cases, while the remaining five cases were both light and heavy chains. The inhibitor titer was considerably higher for Kogenate, a recombinant fVIII concentrate, than for Haemate P, a fVIII/vWf complex concentrate, in all inhibitor plasmas that had C2 domain specificity. In five inhibitor plasmas with A2 domain specificity and in five with both A2 and C2 domain specificities, Kogenate gave titers similar to or lower than those with Haemate P. The inhibitory effect of IgG of each inhibitor plasma was then compared with recombinant fVIII and its complex with vWf. When compared to the other 10 inhibitor IgGs, IgG concentration, which inhibited 50% of fVIII activity (IC50), was remarkably higher for the fVIII/vWf complex than for fVIII in all the inhibitor IgGs that had C2 domain reactivity. Competition of inhibitor IgG and vWf for fVIII binding was observed in an ELISA system. In 10 inhibitors that had C2 domain reactivity, the dose dependent inhibition of fVIII-vWf complex formation was observed, while, in the group of inhibitors with A2 domain specificity, there was no inhibition of the complex formation except one case. We conclude that a subset of fVIII inhibitors, those that bind to C2 domain determinants, are less inhibitory to fVIII when it is complexed with vWf that binds to overlapping region in the C2 domain.

Macrophages have been shown to be the major population of infiltrated immunocytes at the early stage of insulitis in diabetes-prone BB rats. This study was undertaken to investigate the role of macrophages in the development of insulitis in nonobese diabetic (NOD) mice. Administration of cyclophosphamide to NOD mice resulted in a significant increase in the incidence of overt diabetes and severity of insulitis compared with that in untreated NOD mice. Intraperitoneal injections of silica completely prevented the development of diabetes and insulitis in both cyclophosphamide-treated and untreated animals. Because silica is selectively toxic to macrophages, the results suggest that macrophages play an important role in the initiation of insulitis in NOD mice. Diabetes 37:989-91, 1988 E vidence indicates that many patients with insulindependent diabetes mellitus (IDDM) may result from an autoimmune process directed against pancreatic p-cells (1). Animal models for IDDM, such as BB rats and nonobese diabetic (NOD) mice, support the autoimmune hypothesis. However, the mechanism underlying the autoimmunity remains unknown (1). Various effector systems, e.g., T-lymphocytes, natural killer (NK) cells, macrophages, and/or humoral mediators, have been implicated as the possible effectors of immune responses.Recent studies from our laboratory and others revealed that most infiltrated immunocytes at the early stage of insulitis in BB rats are macrophages (2,3). These findings suggested that macrophages may be involved in the initiation of insulitis. We investigated whether macrophages have an initial permissive role in the immune response against pancreatic pcells in NOD mice. MATERIALS AND METHODSOur NOD mouse colony was produced from a breeding stock obtained from Clea Japan (Tokyo). These animals were maintained on regular rat chow and tap water ad libitum at the University of Calgary. Beginning at ~8 wk of age, their urinary glucose and ketone levels were determined twice weekly with Diastix and Ketostix reagent slips (Miles, Ontario, Canada). Individual mice were classified as diabetic on the basis of positive glycosuria. The overall cumulative incidence of diabetes among the colony was -1 5 % in males and 50% in females at 24 wk of age.A total of 32 male animals from 10 litters, divided into four groups (n = 8/group), were used for this study. We injected silica (Steinkohlen-Bergbau-Verein, Essen, FRG), at a dose of 200 mg • kg~1 body wt • wk~1 i.p., into one group of animals from 4 to 10 wk of age. The second group of animals received silica, as described above, and subsequently cyclophosphamide (Homer, Montreal, Canada), at a dose of 150 mg/kg body wt twice per 3-day interval, at age 10 wk. The third group received only cyclophosphamide, administered at a dose identical to the second group. The fourth group of animals received no chemicals and were used as controls.Two weeks after the second injection of cyclophosphamide, the mice were killed by suffocation with carbon dioxide, and their pancreases were fixed in 6% ...