Continuous measurement of fluid mobilization from ICF space following acute dehydration by dialyzation in dogs

The changes of the distribution of body fluid following acute isotonic dialyzation were studied from the results of continuous monitoring of extracellular fluid volume and physiological parameters. An indicator of extracellular space, 51Cr-EDTA, was injected into splenonephrectomized dogs. After the equilibrium of tracer dilution was attained, 10 ml/kg of plasma water was isotonically withdrawn by means of a dialyzer of hollow fiber type. The volumes of extracellular fluid (ECF) and plasma (PV) were continuously monitored for 80 min and plasma osmolality was measured at 10 min intervals. At the 50-60th min after the fluid modification, the reduction of PV was only 3.8 ml/kg and that of ECF was 4.2 ml/kg. The continuous profile of ECF change showed a significant mobilization of water from intracellular fluid (ICF) soon after the dialyzation. It is concluded that, in the state of hypovolemia, plasma fluid is replenished with the transvascular fluid absorption from interstitial space and that, concomitantly, the reduction of ISF is restituted with the fluid mobilization from ICF into extracellular space within the early stage of 1 hr. Good linear correlation was found between the amount of mobilized water from ICF and the increment of plasma osmolality. An increase in osmotic force was considered the mechanism which caused the fluid shift. These findings suggest that the change in plasma osmolality is a good predictor of mobilized volume from ICF in hypovolemia. The effects of inverse fluid modification, i.e., isotonic infusion, were also compared.     

Granulocytic sarcoma presenting with lymph node infarction at disease onset

A completely infarcted lymph node is an unusual event. However, lymph node infarction should alert the pathologist to the considerable likelihood of malignant lymphoma. We report two unusual cases of acute myeloid leukemia presenting with granulocytic sarcoma at disease onset with a lymph node lesion exhibiting extensive lymph node infarction. The infarcted tissue contained numerous eosinophilic cell ghosts. There were some islands of degenerated, pyknotic medium-sized nuclei resembling lymphoblasts present in the necrotic area. By immunohistochemistry, these medium sized cells were CD3-, CD20-, CD34+, CD43+, CD45RO-, CD68-, CD79a- and myeloperoxidase+ in both cases. Differentiation of granulocytic sarcoma from malignant lymphomas is important for adequate therapy. The present cases indicate that granulocytic sarcoma should be added to the list of differential diagnoses for lymph node infarction.     

Phenotyping of proliferating lymphocytes in angioimmunoblastic lymphadenopathy and related lesions by the double immunoenzymatic staining technique.

Biopsy specimens of lymph nodes with the histologic characteristics of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) were obtained from 9 cases (4 cases of AILD and 5 cases of AILD-like T lymphoma [AILD-T]) and histologically analyzed by the use of a double immunoenzymatic staining technique with the combination of a monoclonal antibody against lymphocyte membrane antigen and that against human DNA polymerase alpha (pol alpha), which is detectable in the nucleus of the cells in G1, S, and G2 phases. In all 9 cases, the pol alpha + proliferating cells had a peripheral T-cell phenotype with T11 and Leu-4 antigens, whereas proliferating B cells with B1 antigen were rarely observed. As for T-cell subset antigens, the proliferating T cells had T4+ helper/inducer phenotype in 7 cases, while T8+ suppressor/killer T cells proliferated in 2 cases, although a significant number of T4+ proliferating cells were also recognized. The study on malignant lymphomas that evolved in the 2 cases showed that the T-subset antigens on major proliferating tumor cells were the same as those found in the preceding AILD lesions, suggesting that lymphoma T cells originate from the AILD lesion. The results suggested that AILD without histologic manifestations of malignancy and AILD-T may be a neoplastic disease derived from either subset of peripheral T cells.     

The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis

PTEN is an important tumor suppressor gene. Hereditary mutation of PTEN causes tumor-susceptibility diseases such as Cowden disease. We used the Cre-loxP system to generate an endothelial cell-specific mutation of Pten (Tie2CrePten) in mice. Tie2CrePten(flox/+) mice displayed enhanced tumorigenesis due to an increase in angiogenesis driven by vascular growth factors. This effect was partially dependent on the PI3K subunits p85alpha and p110gamma. In vitro, Tie2CrePten(flox/+) endothelial cells showed enhanced proliferation/migration. Tie2CrePten(flox/flox) mice died before embryonic day 11.5 (E11.5) due to bleeding and cardiac failure caused by impaired recruitment of pericytes and vascular smooth muscle cells to blood vessels, and of cardiomyocytes to the endocardium. These phenotypes depend strongly on p110gamma rather than on p85alpha and were associated with decreased expression of Ang-1, VCAM-1, connexin 40, and ephrinB2 but increased expression of Ang-2, VEGF-A, VEGFR1, and VEGFR2. Pten is thus indispensable for normal cardiovascular morphogenesis and post-natal angiogenesis, including tumor angiogenesis.     

Effect of increased task procedures on correlation dimensions of the electroencephalogram

Changes in correlation dimensions of the electroencephalogram (EEG) were examined in three different tasks. These three tasks differed from each other with respect to the number of procedures. In the present experiment, left-hand movement and mental arithmetic were controlled, respectively, during an auditory linguistic task. Subjects were 13 healthy right-handed males. EEG signals from eight electrode sites were analyzed and the correlation dimensions were obtained. In addition, the relative power was obtained for the alpha band. An increase in the number of procedures yielded high dimensionality on the occipital EEG. In contrast, left-hand movement had no significant effect on EEG dimensions over the motor area. The relative power of the alpha band was seen to decrease in all channels as the number of procedures increased. The fact that changes in EEG dimensions did not necessarily exhibit a simple correspondence to changes in alpha wave activity was also discussed.     

Melanocyte lysis by cytotoxic T lymphocytes recognizing the MART-1 melanoma antigen in HLA-A2 patients with Vogt Koyanagi Harada disease

The MART-1/Melan-A melanoma antigen recognized by the majorityof HLA-A2-restricted tumorinfiltrating lymphocytes is a selfantigen expressed on melanocytes and the retina. We have investigatedwhether Vogt–Koyanagi–Harada (VKH) disease and sympatheticophthalmia (SO), systemic inflammatory disorders affecting variousorgans containing melanocytes, are autoimmune diseases directedtoward the MART-1 antigen. In two of three patients with VKHdisease and one patient with SO, CD8⁺ T cell clones (TCC) fromintraocular fluid of HLA-A2⁺ patients lysed T2 cells when pulsedwith a HLA-A2-binding MART-1 peptide, but not a HLA-A2-bindingpMel-17 or tyrosinase peptide, in a HLA-A2-restricted manner.These CD8⁺ TCC lysed both melanocytes and melanoma cells ina HLA-A2-restricted manner. In addition, CD8⁺ TCC recognizinga HLA-A2-binding MART-1 peptide were also established from peripheralblood mononuclear cells of a patient with VKH disease. In contrast,either CD4⁺ TCC from these patients or CD8⁺ TCC from the intraocularfluid of HLA-A2⁺ patients with uveitis associated with Behcet'sdisease or HTLV-I uveitis did not show this cytotoxicity. Theresults demonstrate that the MART-1 peptide-specific cytotoxicT lymphocytes lyse melanocytes in the eye of patients with VKHdisease or SO, suggesting that these diseases are autoimmunediseases directed toward the MART-1 antigen in HLA-A2⁺ patients.     

Analysis of three compartments of extracellular fluid in dog

The distribution kinetics of an extracellular volume tracer 51Cr-EDTA was analysed from the results of continuous monitoring of plasma radioactivity. 51Cr-EDTA was injected intravenously into spleno-nephrectomized dogs by a single injection, and the radioactivity of circulating blood and physiological parameters were continuously monitored for 150 min. The dilution curve of radioactivity was resolved into 4 components, and expressed as c(t) = Ae-alpha t + Be-beta t + Ce-gamma t + D. The half-times of each term were 0.51, 2.41, and 19.26 min, respectively. Based on this result, 51Cr-EDTA space was divided into 3 compartments--plasma volume (V0), rapidly diffusing interstitial fluid (V1), and slowly diffusing interstitial fluid (V2). To explain the distribution of the tracer among these fluid spaces, two possible models were proposed. In the "tandem model" the volume of each compartment was calculated as 59.2, 121.7, and 101.7 ml/kg of body weight, respectively, and the mobility index of the tracer from V0 to V1 was 5.1 times as great as that from V1 to V2. In the "parallel model" the volumes were 59.2, 72.3, and 151.1 ml/kg of body weight and the mobility index of the tracer from V0 to V1 was 3.3 times as great as that from V0 to V2. The characteristics of each model were discussed in relation to the properties of the interstitial space.