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Biomedical subjects

P Fishman

Publications and source records attributed to P Fishman.

At least 19 recordsLinked to original sources

The association of cervical spondylosis and multiple sclerosis.

The diagnostic and therapeutic considerations produced by the coexistence of cervical spondylosis and multiple sclerosis are complex. We have encountered six patients, affected by both multiple sclerosis and cervical spondylosis, in whom neurosurgical procedures were performed. The diagnosis of multiple sclerosis was confirmed by a combination of clinical, neuroimmunologic, electrophysiologic, and neuroradiologic findings. The diagnosis of spondylosis with spinal cord compromise was confirmed by myelography and computed tomographic scan in all cases, and by magnetic resonance imaging in four. Surgery was followed by lasting clinical improvement in two patients, transient improvement in one, and no change in the other three. Our experience confirms that multiple sclerosis and cervical spondylosis can coexist and suggests that this coexistence may result in an interaction that compounds the deleterious effect on the nervous system. Diagnostic evaluations of patients, particularly young patients, with symptoms of cervical spondylosis should include consideration of the possible coexistence of multiple sclerosis. The evaluation of a patient with known multiple sclerosis who develops new signs of cervical spinal cord dysfunction should always include spinal neuroimaging studies. When progression of symptoms coincides with documented progression of anatomic compression, surgical intervention can yield good results.

Adult

Interleukin-3-like activity levels in pregnant women: possible modulation by progesterone.

Human interleukin-3-like activity (IL-3-LA), a factor possessing similar characteristics to interleukin-3 and having clony stimulating factor (CSF) activity, has recently been defined. In the present study, IL-3-LA levels in the sera of women before and after delivery were examined. The results indicate a significant increase in IL-3-LA levels in women before delivery as compared to IL-3-LA levels after delivery or to non-pregnant healthy women. The ability of mononuclear cells from women before and after delivery to produce IL-3-LA was similar to that of mononuclear cells from cord blood. In addition, the effect of progesterone on in vitro IL-3-LA production was examined and a stimulatory dose-dependent effect was observed. These observations point to the hypothesis that during pregnancy IL-3-LA levels are modulated by progesterone. With placental loss, the IL-3-LA in the sera decreases, although the mononuclear cells previously affected by the hormone continue to produce cytokines.

Female

Cultured human cord blood cells spontaneously produce a factor with basophil-promoting activity.

Cord blood is a source for pluripotential stem cells capable of differentiating into various hemopoietic cell lines in the presence of suitable specific growth factors. Without additional growth factors, cultured cord blood cells give rise to large numbers of basophils. We have recently defined a human basophil growth promoting factor, designated as interleukin-3-like activity (IL-3-LA), produced spontaneously by human monocytes and lymphocytes. In order to explain the phenomenon of spontaneous basophil development in cord blood cultures, we studied the relationship between basophil production and IL-3-LA release in these cultures. IL-3-LA produced by cord blood mononuclear cells increased from day 3 to day 14 and then decreased gradually by day 35. Basophil development was observed from day 14 on (33% +/- 6.4) and peaked on day 21 (51% +/- 7.4). Histamine release followed the same pattern i.e., 10 +/- 3.4 ng/ml on day 14, and 23 +/- 6.5 ng/ml on day 21. It is suggested that IL-3-LA spontaneously released by cord blood mononuclear cells induces basophil development in these cultures.

Basophils

The putative role of cytokines in the induction of primary anti-phospholipid syndrome in mice.

Antiphospholipid syndrome (APLS) is characterized by thrombocytopenia, thromboembolic phenomena and recurrent fetal loss, associated with anti-cardiolipin antibodies (ACA) and/or lupus anticoagulant. The syndrome may be primary or may be associated with other conditions such as systemic lupus erythematosus (SLE). In this study we induced primary APLS following immunization of BALB/c mice with a human monoclonal ACA (H-3). Analysis of the cytokine profile of the mice with experimental APLS indicated low production of IL-2, IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by concanavalin A (Con A)-stimulated splenocytes of H-3 immunized mice. It seems that the low levels of IL-3 and GM-CSF have a potential role in the fetal loss of the APLS. Whatever the mechanism of IL-3 and GM-CSF in preventing fetal loss, these results may have therapeutic bearing on the reproductive outcome in women and other species with APLS.

Animals

Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3).

Antiphospholipid syndrome (APLS) is characterized by thrombocytopenia, thromboembolic phenomena, and recurrent fetal loss, associated with anticardiolipin antibodies (ACA) and/or lupus anticoagulant. The syndrome may be primary or may be associated with other conditions such as systemic lupus erythematosus. We have previously shown the ability to induce APLS in naive mice following passive transfer of serum and monoclonal ACAs. Similarly we generated the secondary APLS in BALB/c mice following immunization with a pathogenic anti-DNA antibody. In the current study we report on the induction of primary APLS following immunization of BALB/c mice with a human monoclonal ACA (H-3). The mice developed high persistent titers of ACA. The APLS was characterized by prolonged activated partial thromboplastin time, low fecundity rate (21% vs. 48% of control immunized mice), high resorption index of fetuses (25% vs. 3%), and low weights of embryos and placentae. Our study points to the ability of inducing primary APLS in naive mice. The induction of various presentations of APLS by different ACA may explain the diversity of clinical manifestations seen in patients with APLS.

Animals

Estimating county percentages of people without health insurance.

County data on the percentage of people without health insurance are seldom available, although state program planning requires such information. As part of an evaluation of Washington's Basic Health Plan (BHP), we conducted a telephone survey in nine Washington counties to estimate the percentage of people under the age of 65 who were uninsured. We used regression analysis to estimate the percentage uninsured in a county as a function of the percentage unemployed. Two validation approaches yielded very good results, suggesting that the equation could be used to estimate the percentage uninsured in unsurveyed counties. The variation ranged from 15% to 23% uninsured in the 9 surveyed counties, and was estimated to range from 9% to 35% among the state's 39 counties. With proper caution, estimates based on this equation can probably be used in other states if better data are unavailable.

Data Collection

Spontaneous release of a factor with interleukin-3-like activity by human lymphocytes and monocytes.

The production of a factor with interleukin-3-like activity (IL-3-LA) by cultured human peripheral-blood mononuclear cells has been studied. Culture supernatants spontaneously derived from lymphocytes or monocytes stimulated the proliferative activity of 3 IL-3-dependent cell lines. Purification of this factor by gel filtration-high-pressure liquid chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing demonstrated the presence of a glycoprotein with a molecular weight of 25-30 kilodaltons and an isoelectric point of 7.6. The biochemical characteristics of the IL-3-LA derived from human monocytes and lymphocytes were very similar. The biological activity of the semipurified factor was tested on mononuclear cells from fetal cord blood. It was found that after 21 days 40% of the cells in the culture were mature basophils which released 15-18 ng histamine/10(6) cells.

Basophils

SEM observations on the mechanism of platelet release from megakaryocytes.

Normal human bone marrow megakaryocytes were examined with the scanning electron microscope (SEM) to clarify the mechanism of platelet release. Several types of megakaryocytes were dtected according to their surface appearance, i.e. with wrinkles, ridges, villous formations, round blebs and cells with platelets still attached to the cell membrane. These observations are consistent with the concept that bleb formation is at least one of the mechanisms for platelet liberation.

Blood Platelets

pH-induced platelet ultrastructural alterations. A possible mechanism for impaired platelet aggregation.

After the observation that lavages with alkaline solutions exert a beneficial effect on the bleeding tendency and increase platelet aggregation in patients with intragastric hemorrhage, studies were undertaken to find a relationship between changes of pH and platelet morphology. Transmission and scanning electron microscopy showed that at a pH lower than 7.4, normal human platelets change their internal structure as well as their shape, becoming spheres deprived of pseudopodia. On the other hand, a pH higher than 7.4 induces transformation of platelet internal organelles similar to that caused by thrombin. At an alkaline pH, the platelets develop multiple pseudopodia that facilitate their attachment to each other. These findings may explain the increased platelet aggregation in alkaline medium demonstrated in one of our previous works.

Blood Platelets

The surface ultrastructure of Gaucher cells.

The Gaucher cells of seven patients with Gaucher's disease were examined by both transmission and scanning electron microscopy. The ultrastructure of the cells, as seen by transmission electron microscopy, did not differ from that reported in the literature. The surface structure varied not only in the different patients but also in the same individual. The cells were oval or round, most of them with a rough surface due to presence of microvilli, ruffles, ridges, and blebs of various numbers and shapes. In two patients the Gaucher cells showed phagocytosis. The appearance of the surface ultrastructure of the Gaucher cells supports the accepted view that they are related to the cells of the reticuloendothelial system.

Adolescent

Satellitism of platelets to monocytes in a patient with hypogammaglobulinaemia.

The first case of platelet satellitism to monocytes in a patient with hypogamma-globulinaemia is described. Platelet adherence was observed with heparinized blood and was dependent on the patient's plasma. The ultrastructural findings observed with the transmission (TEM) and scanning electron microscope (SEM) are reported.

Agammaglobulinemia

Ultrastructure of the cells in the peripheral blood of human embryos at early gestational stages.

The presence of the different blood series in the peripheral blood of 10- to 18-week-old human embryos was followed by electron microscopy. It has been demonstrated that the earlier the stage of embryonic development, the more immature cells are found in the peripheral blood. This phenomenon may suggest migration of blood cell progenitors from earlier to more definitive sites of embryonic erythropoiesis.

Blood Cells

SEM observations on Sendai virus-induced fusion of embryonic mouse erythroblasts.

The events of fusion of 11- and 16-day embryonic mouse liver erythroblasts induced by Sendai virus (SV) were followed with the scanning electron microscope (SEM). Erythroid precursors incubated with the virus showed numerous 'pores' on the cell membrane. The cell fusion began with the appearance of a fine 'meshwork' structure between the adjacent cells, followed by a gradual formation of a common cell membrane and terminated with the appearance of polykaryons, in which the nuclei were easily recognized when located in the vicinity of the polykaryon membrane. There was no difference in the process of fusion between erythroblasts at identical and those at different stages of maturation.

Animals

Correlation between movement of concanavalin A membrane receptors and cytolysis. A scanning electron microscopy study.

The present study was undertaken to test whether cytolysis induced by Concanavalin A (Con A) requires lateral mobility of membranal lectin receptor sites into caps. Treatment of interphase murine mastocytoma cells with 10(-4) M colchicine promoted cap formation by Con A in about 30% of the cells, followed by cytolysis. Pretreatment of the cells with NaN3, low temperature, or glutaraldehyde decreased the degree of capping and, to the same extent, the degree of cytolysis. The addition of antibodies to cells bound with Con A increased the appearance of capping and cytolysis. A linear relationship with a high correlation coefficient exists between the degree of capping and cytolysis, suggesting that lateral mobility of membrane Con A receptors is required for cytolysis by the lectin. The process of cap formation by Con A up to the stage of cytolysis was followed by scanning electron microscopy.

Animals

Acid-base balance and plasma composition in the aestivating lungfish (Protopterus).

Upon entering into aestivation, Protopterus aethiopicus develops a respiratory acidosis. A slow compensatory increase in plasma bicarbonate suffices only to partially restore arterial pH toward normal. The cessation of water intake from the start of aestivation results in hemoconcentration and marked oliguria. The concentrations of most plasma constituents continue to increase progressively, and the electrolyte ratios change. The increase in urea concentration is disproportionately high for the degree of dehydration and constitutes an increasing fraction of total plasma osmolality. Acid-base and electrolyte balance do not reach a new equilibrium within 1 yr in the cocoon.

Acclimatization