Hemopoietic growth factors regulate the survival of human basophils in vitro.

Human basophils were purified from normal peripheral blood, using density gradient followed by negative panning selection. We tested the effects of hemopoietic growth factors on the survival of these basophils in vitro. In the absence of exogenous factors, basophils (purity greater than 90%) decreased in number rapidly. At day 7 only 11% of the cells remained alive in cultures; less than 1% of cells survived at day 14. Interleukin (IL)-3 maintained numbers of viable cells; cell viability was 67% at day 7 and 45% at day 14. Granulocyte-macrophage (GM)-colony-stimulating factor (CSF) exhibited slight effect on the survival; 33% of cells remained at day 7. Other growth factors including granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no significant effect on the survival of basophils at all. Morphological and functional characterization of cells maintained by IL-3 revealed that they belonged to the basophil lineage. These observations indicate that normal basophils possess functional receptors for IL-3 and GM-CSF and that both factors modulate immediate- and delayed-type hypersensitivity reactions by prolonging the life span of basophils.     

LYMPHOMATOID GRANULOMATOSIS: Light Microscopic, Electron Microscopic and Immunohistochemical Study

A case of lymphomatoid granulomatosis (LYG) involving the lungs, skin, stomach, and possibly the left kidney in a 60-year-old man is presented. The infiltrates in the lungs, stomach, and skin showed a polymorphic appearance, and consisted predominantly of lymphocytes of mature and blastic form and of a few neutrophils, plasma cells, and histiocytes. Most lymphoid cells showed irregularly shaped nuclei and clustered dense bodies, characteristics indicative of T lymphocytes. An immunohistochemical study confirmed the T cell origin of the lymphocytes; i.e. they were positive for Leu-1, Leu-3a and la-like antigens but negative for Leu-2a antigen and the antibodies against light chains. The homogeniety of the major population of infiltrates in LYG indicates that at least some forms of LYG may be neoplastic or pre-neoplastic lymphocytic disorders which may ultimately progress to malignant lymphoma. ACTA PATHOL. JPN. 35 : 711–721, 1985.     

Infiltrating eosinophils and eotaxin: their association with idiopathic eosinophilic esophagitis.

BACKGROUND: Idiopathic eosinophilic esophagitis (IEE) is a very rare disease characterized by thickening and eosinophil infiltration of the esophagus. The most potent chemotactic factor for eosinophils is eotaxin, and its pathophysiologic significance in IEE needs to be elucidated. OBJECTIVE: To study the association between eotaxin and IEE. METHODS: We examined eotaxin expression in the esophagus of an IEE patient in comparison to controls by immunohistochemistry using a monoclonal antibody for human eotaxin. We also measured the free eotaxin level and the total (free and bound-form) eotaxin level in blood by enzyme-linked immunosorbent assay before and after the initiation of steroid therapy. RESULTS: Most of the infiltrating eosinophils in the affected esophageal tissue showed immunohistochemical staining with anti-eotaxin antibody. In blood samples, the free eotaxin level was slightly elevated before treatment, whereas the total eotaxin level was within the normal range. Unexpectedly, the total eotaxin level increased dramatically after the initiation of steroid therapy, whereas the increase of free eotaxin was modest. CONCLUSION: Infiltrating eosinophils that express eotaxin and the changes of blood eotaxin levels during steroid therapy suggest that eotaxin may be associated with IEE.     

The levels of cerebrospinal fluid Abeta40 and Abeta42(43) are regulated age-dependently

Decreased levels of cerebrospinal fluid (CSF) Abeta42 is a diagnostic marker of Alzheimer's disease. To clarify the biological basis of this marker, the physiological alterations of CSF Abeta40 and Abeta42 by aging were studied. CSF samples from 92 normal subjects between 8 and 89 years old were measured using a specific ELISA for Abeta40 and Abeta42(43). High concentrations of Abeta40 and Abeta42(43) in the young group, under 29 years old, changed to be at low concentrations in the adult group between 30 and 59 years old. Subsequently, the levels increased again with age. Third order regression analysis showed a significant correlation between the levels of Abeta40 and age (Y = - 169 X(3) + 3.1X(2)- 0.02X + 4135; P < 0.034) and between the levels of Abeta42(43) and age (Y = - 46 X(3) + 0.9 X(2)- 0.005X + 992; P < 0.005). The levels of CSF Abeta40 and Abeta42(43) were physiologically regulated to show a U-shaped natural course in normal aging. These findings suggested that the physiological increase of Abeta42(43) over 59 years of age is selectively inhibited in Alzheimer's disease.     

Expression of CD56 antigen on acute nonlymphocytic leukemia]

CD56 antigen (detected by NKH-1) is distributed on NK cells, monocytes, and ectodermal neural cells. In this study, the blasts of 29.2% of 27 patients with acute nonlymphocytic leukemia (ANLL) expressed CD56 antigen, but not CD16, CD2, or CD3 antigen. Leukemic cells isolated from 3 patients with CD56-positive ANLL did not have NK activity. There were no significant differences between CD56-positive and CD56-negative ANLL in CD13-positive cases, CD33-positive cases, and HLA-DR-positive cases. These results suggest that CD56-positive ANLL could be so-called mixed-lineage leukemia (lymphoid-associated antigen in ANLL).     

Fundamental morphological changes in human olivary hypertrophy.

Morphological features of neurons in human inferior olivary nuclei were studied in 6 autopsied patients with dentato-olivary pathway lesions, who had survived for between 6 days and 15 months. Central chromatolysis-like neuronal enlargements were already present in the acute cases. Electron microscopy revealed round, homogeneous and electron-dense granules, varying in diameter from 0.15 micron to 2.5 microns, occurring frequently within the rough endoplasmic reticulum (ER) in the chromatolytic neurons of all 6 patients. No similar granules were observed in 6 controls. The vacuoles were due to dilatation of the rough ER, and often contained floccular materials. Neurofilamentous hyperplasia in the neurons was more frequently seen in the chronic cases. These findings suggest that the fundamental changes in the neurons in olivary hypertrophy occur within the rough ER.     

Alpha 1-antichymotrypsin has a trophic effect on hippocampal neurons in vitro

alpha 1-Antichymotrypsin (ACT) has been reported to be present in senile plaques, and ACT level is elevated in the sera of patients with Alzheimer's disease. We found that ACT has a neurotrophic activity in vitro, i.e., it enhanced neuronal survival under the culture conditions used. Hippocampal neurons were cultured in chemically defined medium containing ACT at various concentrations. In order to evaluate the number of surviving neurons semiquantitatively, enzyme immunoassay for microtubule-associated protein2 (MAP2) was carried out using anti-MAP2 antibody. Cells cultured in medium containing 4 micrograms/ml of ACT showed 1.8-fold more neurotrophic activity than those cultured without ACT.     

Second-order vestibular neuron morphology of the extra-MLF anterior canal pathway in the cat

Second-order vestibular neurons form the central links of the vestibulo-oculomotor three-neuron arcs that mediate compensatory eye movements. Most of the axons that provide for vertical vestibulo-ocular reflexes ascend in the medial longitudinal fasciculus (MLF) toward target neurons in the oculomotor and trochlear nuclei. We have now determined the morphology of individual excitatory second-order neurons of the anterior semicircular canal system that course outside the MLF to the oculomotor nucleus. The data were obtained by the intracellular horseradish peroxidase method. Cell somata of the extra-MLF anterior canal neurons were located in the superior vestibular nucleus. The main axon ascended through the deep reticular formation beneath the brachium conjunctivum to the rostral extent of the nucleus reticularis tegmenti pontis, where it crossed the midline. The main axon continued its trajectory to the caudal edge of the red nucleus from where it coursed back toward the oculomotor nucleus. Within the oculomotor nucleus, collaterals reached superior rectus and inferior oblique motoneurons. Some axon branches recrossed the midline within the oculomotor nucleus and reached the superior rectus motoneuron subdivision on that side. Since these neurons did not give off a collateral toward the spinal cord, they were classified as being of the vestibulo-oculomotor type and are thought to be involved exclusively in eye movement control. The signal content and spatial tuning characteristics of this anterior canal vestibulo-oculomotor neuron class remain to be determined.