Three Kinds of Foamy Cells in the Spleen: Comparative Histochemical and Ultrastructural Studies

By light and electron microscopy, we observed foamy cells in the spleens from a patient with hemolytic anemia due to red cell adenosine deaminase (ADA) overproduction, a patient with rheumatoid arthritis (RA) treated with gold, and patients with idiopathic thrombocytopenic purpura (ITP)

The foamy cells associated with red cell ADA overproduction were essentially similar to Gaucher-like cells described in patients with thalassemia, and it was suggested that the accelerated destruction of red cells was one of the factors responsible for the development of foamy cells. Foamy cells in ITP and RA were closely associated with an increased destruction of platelets in the spleen. Morphologic transitions between phagocytosed platelets and myelinlike materials were traced in these disorders. In RA, however, foamy cells were heterogeneous from an ultrastructural standpoint, with different cytoplasmic inclusions. In addition to myelinlike materials, dense bodies, vacuoles with flocculent materials, and gold were noted in most of foamy cells. As gold compounds are known to inhibit lysosomal enzymes, we surmise that an acquired disturbance in lysosomal digestion is partially responsible for the accumulation of intermediate metabolites.

In the pathogenesis of foamy cells associated with blood cell dyscrasia, the accelerated destruction of blood cells and/or acquired disorders in catabolic pathways within the macrophages are suggested to be the underlying mechanism of an intralysosomal accumulation of incompletely degraded cellular debris.     

Malignant Cystosarcoma Phyllodes Of Prostate

A case of malignant cystosarcoma phyllodes of the prostate is reported in a 45-year-old male. This tumor was composed of benign columnar or squamous cystic folds and sarcomatous stroma including rhabdomyomatous elements. The prostatic origin of the tumor was clearly proved by the unlabeled immunoperoxidase method. ACTA PATHOL. JPN. 34: 663–668, 1984.     

Anxiety Treatment and Targeted Sleep Enhancement to Address Sleep Disturbance in Pre/Early Adolescents with Anxiety

Sleep disturbance is prevalent in anxious youth and prospectively predicts poor emotional adjustment in adolescence. Study 1 examined whether anxiety treatment improves subjective and objective sleep disturbance in anxious youth. Study 2 examined whether a sleep intervention called Sleeping TIGERS can further improve sleep following anxiety treatment. Study 1 examined 133 youth (ages 9–14; 56% female; 11% ethnic/racial minority) with generalized, social, or separation anxiety over the course of anxiety treatment (cognitive behavioral treatment or client-centered treatment). Sleep-related problems (parent-, child-report) and subjective (diary) and objective (actigraphy) sleep patterns were assessed across treatment in an open trial design. Study 2 included 50 youth (ages 9–14; 68% female; 10% ethnic/racial minority) who continued to report sleep-related problems after anxiety treatment and enrolled in an open trial of Sleeping TIGERS. Pre- and postassessments duplicated Study 1 and included the Focal Interview of Sleep to assess sleep disturbance. Study 1 demonstrated small reductions in sleep problems and improvements in subjective sleep patterns (diary) across anxiety treatment, but outcomes were not deemed clinically significant, and 75% of youth stayed above clinical cutoff. Study 2 showed clinically significant, large reductions in sleep problems and small changes in some subjective sleep patterns (diary). Anxiety treatment improves, but does not resolve, sleep disturbance in peri-pubertal youth, which may portend risk for poor emotional adjustment and mental health. The open trial provides preliminary support that Sleeping TIGERS can improve sleep in anxious youth to a clinically significant degree.     

Chitosan hydrogel as a drug delivery carrier to control angiogenesis

An aqueous solution of photocrosslinkable chitosan containing azide groups and lactose moieties (Az-CH-LA) incorporating paclitaxel formed an insoluble hydrogel within 30 s of ultraviolet light (UV) irradiation. The chitosan hydrogel showed strong potential for use as a new tissue adhesive in surgical applications and wound dressing. The fibroblast growth factor (FGF)-2 molecules retained in the chitosan hydrogel and in an injectable chitosan/IO₄-heparin hydrogel remain biologically active, and were gradually released from the hydrogels as they biodegraded in vivo. The controlled release of biologically active FGF-2 molecules from the hydrogels caused induction of angiogenesis and collateral circulation occurred in healing-impaired diabetic (db/db) mice and in the ischemic limbs of rats. Paclitaxel, which is an antitumor reagent, was also retained in the chitosan hydrogel and remained biologically active as it was released on degradation of the hydrogel in vivo. The chitosan hydrogels incorporating paclitaxel effectively inhibited tumor growth and angiogenesis in mice. The purpose of this review is to describe the effectiveness of chitosan hydrogel as a local drug delivery carrier for agents (e.g., FGF-2 and paclitaxel) to control angiogenesis. It is thus proposed that chitosan hydrogel may be a promising new local carrier for drugs such as FGF-2 and paclitaxel to control vascularization.     

Computational simulations of mitral regurgitation quantification using the flow convergence method: Comparison of hemispheric and hemielliptic formulae

Mitral regurgitation results from the incomplete closure of the mitral valve, and the noninvasive diagnosis of this disease remains an important clinical goal. In this study, steady flow computer simulations were used to evaluate flow convergence method for flow rate estimation. The hemispheric and hemielliptic formulae were compared for accuracy in the presence of complicating factors such, as ventricular confinement, orifice shape, and aortic outflow. Results showed that in the absence of aortic outflow and ventricular confinement, there was a plateau zone where the hemispheric formula approximated the true flow rate, independent of orifice shape. However, in the presence of complicating factors such as aortic outflow and ventricular confinement, there was no clear zone where the hemispheric formula could be applied. The hemielliptic formula, however, worked in, all cases, regardless of chamber size or magnitude of aortic outflow. Therefore, application of the hemielliptic formula shold be considered in future clinical studies.     

Platelet-activating factor in Japanese cedar pollinosis

Japanese cedar pollinosis is a typical allergic disease and has recently become a big social problem. Many population are suffering from this disease every year from the end of February to the beginning of April. In this study, we planned to examine the role of platelet-activating factor (PAF) in this disease, because PAF has been known to be one of the potent chemical mediators in allergic and inflammatory reactions and many evidences indicate that PAF is deeply involved in the pathogenesis of bronchial asthma, a typical allergic disease. We measured the concentrations of the PAF derivative (lyso-PAF) in serum from patients with cedar pollinosis during the pollen season. The level of lyso-PAF in serum from untreated patients with cedar pollinosis (87.8 +/- 8.7 unit.) was significantly higher than that in healthy control (54.9 +/- 7.7 unit.). We also tested the effect of an anti-allergic drug on the level of serum lyso-PAF of cedar pollinosis. Eighteen pairs of serum samples from patients with cedar pollinosis were employed in this study. Lyso-PAF levels after two weeks' therapy with ketotifen (2 mg/day), an anti-allergic drug, decreased the levels significantly (from 82.6 unit to 41.3 unit). These results suggest that PAF could play some important role in cedar pollinosis and that the clinical effect of anti-allergic drug could be partially due to the anti-PAF action.     

Different susceptibilities of long-term potentiations in CA3 and CA1 regions of guinea pig hippocampal slices to nootropic drugs

Effects of the nootropic drugs, piracetam and bifemelane, on long-term potentiation (LTP) of population spikes in the CA3 and CA1 regions of guinea pig hippocampal slices were investigated. Piracetam (10(-6) to 10(-4) M) and bifemelane (10(-8) to 10(-6) M) significantly augmented the LTP in the CA3 region. The effects of these drugs were inhibited by scopolamine (10(-6) M). However, the LTP in the CA1 region was not affected by piracetam and bifemelane even at highly effective concentrations (10(-5) and 10(-6) M, respectively). Thus, the LTP in the CA3 is more susceptible to nootropic drugs than in the CA1.     

Foamy cells in itp spleens and in granulomas induced by murine platelets, commercialized phospholipids, and erythrocyte membrane. Histological and ultrastructural studies

A large number of foamy cells were noted in the spleens from fourteen ITP patients, and two patients who received a large amount of platelet rich plasma. Using the unlabelled immunoperoxidase method, these foamy cells were shown to contain platelet antigen. Platelets in varying stages of intracellular digestion, from intact-appearing forms to myelin-like materials, were disclosed in foamy cells. Foamy cells were experimentally induced in granulomas by subcutaneous injection of platelets with or without accompanied administration of steroid, the platelets reacted with anti-murine platelet antibody, commercialized phospholipids (PE, PC, SM, PS, and the mixture of them), and the red blood cell membrane. The foamy cells induced by the subcutaneous injection of platelets are similar to those in the spleens of ITP patients. The lipid in foamy cells is chiefly derived from the membrane phospholipid of injected platelets. Concentric myelin-like materials were also noted in the foamy cells after injection of erythrocyte membrane. The myelin-like materials in these foamy cells are similar to those appearing in macrophages following injection of PC and SM. This suggests that these phospholipids derived from cell membrane are more resistant to intracellular digestion by lysosomal enzymes. We conclude that the foamy appearance of the cordal macrophage in ITP spleens results from incomplete intracellular degradation of platelet membrane.