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In a series of electron microscopic studies of human urinary stones, a stone composed of sodium orthophosphate hydrate was identified. The stone was recovered from a patient who succumbed to advanced renal failure. A massive failure of the sodium pump, which cotransports phosphate across the brush border membrane of the proximal tubules is thought to be responsible for such an exceptional stone. This appears to be the first description of sodium phosphate crystal in a human urinary stone. Electron microscopy is a useful tool for stone analysis.

Using a monoclonal anti-human IgE receptor (Fc epsilon R) antibody, the percentage of Fc epsilon R(+) cells among peripheral blood lymphocytes in children with or without allergic disorders was determined. The percentage of Fc epsilon R(+) cells in 63 nonallergic children was 4.3 +/- 1.5%, which did not vary with age and was equal to that of adults (4.2 +/- 1.2%). Allergic younger children (0-2 yr) showed a significantly higher percentage of Fc epsilon R(+) cells (7.7 +/- 3.0%) than nonallergic younger children (0-2 yr) (4.0 +/- 1.3%, p less than 0.001). Similarly, in allergic younger children, serum IgE levels (geometric mean = 58.9 IU/ml) were also significantly higher than those of nonallergic younger children (geometric mean = 2.0 IU/ml) (p less than 0.01). A positive correlation between the percentages of Fc epsilon R(+) cells and serum IgE levels was observed (Spearman rank = 0.88, p less than 0.01] in eight allergic younger children (0-2 yr) with serum IgE levels higher than 100 IU/ml. The increase in the percentage of Fc epsilon R(+) cells in allergic younger children (0-2 yr) was not a secondary phenomenon caused by serum IgE because serum IgE levels in these children were much lower than the concentration at which IgE enhance Fc epsilon R expression on lymphocytes. In conclusion, Fc epsilon R(+) lymphocytes may play a regulatory role in IgE synthesis in allergic younger children (0-2 yr).

A common acute lymphoblastic leukemia (ALL) cell line, designated LC4-1, was established from peripheral blood mononuclear cells of a patient with acute non-T-cell ALL. LC4-1 cells were characteristically positive for Ia, B4, and common ALL antigens (CALLA), but negative for B2, Tac, T3, T4, T8, T11, and M1 antigens and E-rosette formation. Approximately 30% of LC4-1 cells expressed detectable amounts of B1 antigens. LC4-1 cells expressed neither Epstein-Barr-virus-associated nuclear antigen (EBNA), cytoplasmic immunoglobulins (cIg) nor surface immunoglobulins (sIg). Gene rearrangements had already occurred in LC4-1 in the D-J region of immunoglobulin heavy chain genes, but not in T-cell receptor (beta-chain) genes, suggesting that LC4-1 is a progenitor cell line of B-cell lineage earlier than pre-B-cells. The expression of cell surface antigens of LC4-1 was changed by treatment with 4-phorbol 12-myristate 13-acetate (PMA) (0.1 ng/ml) for 2 days. Before treatment with PMA, about 98% of LC4-1 cells were positive for B4, CALLA, and Ia. However, following treatment they lost CALLA expression without any change in expression of Ia and B4. There was no change in B1-positive population. The change in surface antigens on LC4-1 cells seems to be due to differentiation induced in the cells by PMA. These results support the hypothesis that CALLA is a differentiation antigen and suggest one possible differentiation pathway for pre-B-cells.

Calcium oxalate stones are very common and increasing. Crystal growth is no less important than the crystal nucleation in the pathogenesis of stone formation. The crystal growth was studied in human calcium oxalate stones by a combined electron microscopy and x-ray diffraction. The main mode of weddellite growth was interpenetration twinning of tetrahedral bipyramids. Bipyramids may form as initial crystal seeds, develop from anhedral crystals (crystals which lack flat symmetric faces) of spherular or mulberry shape, develop on the surface of preformed bipyramids by spiral dislocation mechanisms, or develop on whewellite crystal by heterogeneous nucleation and epitaxy. Heterogeneous nucleations of whewellite on weddellite, and calcium apatite on whewellite were also observed. Whewellite grew mainly by parallel twinning. Interpenetration twinning was exceptional. Transformation of anhedral to euhedral (completely bounded by flat faces that are set ar fixed angles to one another) whewellite occurred by parallel fissurations followed by brick wall like stacking of the crystals, while euhedral transformation of weddellite occurred by protrusion of bipyramids frm anhedral crystal surface. Occasionally, an evidence of crystal dissolution was noted. Although an aggregation of crystals is believed to play a pivotal role in stone nidus formation, growth in size of the formed crystals, and twinning and epitactic crystal intergrowth apparently play a significant role in the obstructive urinary stone formation.

Cord blood mononuclear cells produced lower burst-promoting activity (BPA) than adult peripheral blood mononuclear cells when stimulated with phytohemagglutinin (PHA). In order to examine the cellular basis of the low production of BPA by PHA-stimulated cord blood mononuclear cells in the context of the functional immaturity of T cells or monocytes, we studied BPA production by T cells or monocytes from cord blood and adult peripheral blood. Cord T cells produced as much BPA as adult T cells. Monocytes themselves did not produce significant BPA at the concentration used in this experiment (1 x 10(5)/ml). BPA production by adult T cells was significantly enhanced by the presence of autologous monocytes. BPA production by cord T cells was also enhanced by the presence of adult monocytes but not by that of cord monocytes. Cord monocytes did not enhance BPA production by adult T cells either. These results indicate that cord monocytes are primarily responsible for the low BPA production by PHA-stimulated cord mononuclear cells.

Calcification is common in human placentas and is widely recognized as a normal part of maturation and aging of this organ. Eleven human placentas were studied by light and electron microscopy to elucidate the mechanism of placental calcification. Earliest mineral deposits were seen along the trophoblastic basement membrane of the chorionic villi undergoing fibrinoid degeneration. Transmission electron microscopic examination revealed crystalline deposits within small membrane-bound vesicles; the latter appear to be derived from degenerating cells and were particularly numerous within the basement membrane. X-ray microanalysis of these deposits revealed calcium and phosphorus peaks and the pattern of calcium hydroxyapatite was noted by electron diffraction. This pattern of calcification, i.e., precipitation of calcium hydroxyapatite in association with extracellular membrane bound vesicles, is similar to that seen in physiologic and pathologic calcifications of other tissues.

An entirely satisfactory and physiologic solution to adduct paralyzed vocal cord during phonation, coughing, and swallowing has not yet been achieved. The authors noticed that velopharyngeal closure takes place simultaneously with adduction of vocal cords in order to perform phonation, coughing, and swallowing. We devised a new laryngeal pacing system to adduct the paralyzed vocal cord, utilizing velopharyngeal closure under magnetic control. Two mongrel dogs were anesthetized and the interior of the larynx was exposed using a Lynch suspension laryngoscope. A small magnet wrapped by thin Silastic was inserted into the nasal side of the soft palate via a small incision. After making a vertical midline neck incision, the pharynx was dissected and the Gaussmeter probe was inserted into the retropharyngeal space. The Gaussmeter probe was connected to the Gaussmeter and finally to the pacemaker. Electrodes were inserted into the paralyzed adductor laryngeal intrinsic muscles via punctures of the cricothyroid membrane. When the pacing system operated, arbitrarily elevated soft palate to the posterior pharyngeal wall brought about an abrupt increase in magnetic force and thus obvious adduction of the paralyzed vocal cords could be seen.

Deposition of calcium-containing apatite mineral occurs widely in association with cardiovascular and noncardiovascular medical devices and biomaterials, is the leading cause of failure of contemporary bioprosthetic heart valves, and limits the functional lifetime of experimental (and potentially clinical) mechanical blood pumps and polymeric heart valves. Calcification of bioprosthetic tissue is primarily intrinsic, related to cuspal connective tissue cells and fragments, and collagen. In contrast, the predominant site of calcific crystals on flexing polymeric surfaces in blood pumps or valve prostheses is extrinsic, associated with adherent cells, thrombus, or pseudointima. Pathologic calcification shares key features with physiologic skeletal mineralization, including crystal initiation through the mediation of cell membranes, usually in the form of extracellular vesicles. This suggests a unified hypothesis for normal and abnormal mineralization. Several approaches are being studied experimentally for the inhibition of bioprosthetic heart valve calcification. Controlled-release diphosphonate therapy, perhaps in conjunction with an anticalcification cuspal pretreatment, appears most effective. Research objectives in biomaterial-associated calcification include (1) development of animal models, (2) determination of initial crystal nucleation events and sites, (3) elucidation of the relative roles of host, implant, and mechanical determinants, and (4) development of approaches for the inhibition of mineralization.

Fc epsilon receptor (Fc epsilon R) expression on several human cell lines (U937, RPMI 8866, HL 60, THP-1, and Molt 4) and its regulation were examined by immunofluorescent analysis using a monoclonal anti-human Fc epsilon R antibody, H107. Phorbol ester (PMA), recombinant gamma interferon (IFN-gamma) and H107 itself enhanced Fc epsilon R expression on a FC epsilon R positive cell line U937, whereas these reagents did not induce FC epsilon R expression on the Fc epsilon R negative cell lines, Molt 4, HL 60 and THP-1. Dexamethasone not only suppressed by 50% the spontaneous Fc epsilon R expression on U937 cells but also completely inhibited the enhancement of their Fc epsilon R expression on U937 cells induced by PMA, IFN-gamma or H107. Dexamethasone caused a little suppression of Fc epsilon R expression by RPMI 8866 cells. The results showed that Fc epsilon R expression on a human monoblast cell line U937 was up- or down-regulated by a variety of physiological or pharmacological agents. These experimental systems provide a good model for the investigation of the regulatory mechanisms of Fc epsilon R expression.

Calcification of human aortic valve and aortic media occurs regularly, increases with age, and is distinctively associated with a zone of lipid accumulation. Ultrastructurally, the accumulated lipids are seen as cellular degradation products derived from senescent and degenerate fibrocytes and smooth muscle cells. The products when deposited in the matrix are morphologically similar to the matrix vesicles described in other calcifying tissues, and serve as the initial site of calcification rather than collagen or elastic fibers. Scattered among the smaller and more typical matrix vesicles, there are seen frequently giant vesicle-like structures measuring several microns in diameter. Many of these large calcified bodies contain needle-shaped, radially arranged apatite crystal deposits. Some of the large calcifying bodies are bounded by folded structures suggesting a membrane component, at times obscured by a more dense floccular osmiophilic deposition. Alcianophilic apparent proteoglycan particles are also adherent to these large calcified bodies. The substance forming the large calcified bodies might be a complex of phospholipids derived from cell membrane and proteoglycan derived from ground substance, this combination possible serving as a nidus for calcification.

Spheroidal, granular, and fibrillar particles were observed in human aortic valve calcifications. Spheroids were similar to amorphous calcium phosphate shown previously in syn thetic preparations and in bone. The frequent coexistence of needle shaped hydroxyapatite crystals with granular and fibrillar particles suggests that the latter are also amorphous calcium phosphate and may be precursors of hydroxyapatite. All three types of particles had a tendency to form laminated and spherular secondary and failed to give a crystalline pattern by electron diffraction.

Two-stage cell culture assays were used to determine burst-promoting activity (BPA) levels in the plasma of untransfused premature infants during the early anaemic period. The plasma BPA levels decreased during the early phase of the postnatal fall in haemoglobin and the mean plasma BPA levels at 2 and 4 weeks of age were significantly lower (24 +/- 9% and 20 +/- 14%) than those of normal adults (53 +/- 17%). After 8 weeks of age, plasma BPA levels increased markedly in correlation with the recovery of erythropoiesis. Inhibitors of erythroid colony growth were not significantly elevated in the plasma of premature infants. These results suggest that BPA may act as a regulator of erythropoiesis in preterm infants along with erythropoietin.

We investigated the positive and negative effects of IFN-gamma, PMA, dibutyryl cAMP (Bt2cAMP), dexamethasone and transforming growth factor-beta (TGF-beta) on Fc gamma R subtype expression and phagocytosis of a human monoblast cell line, U937. IFN-gamma increased and Bt2cAMP decreased Fc gamma RI expression determined by a mAb 32.2, whereas PMA and Bt2cAMP increased Fc gamma RII expression determined by a mAb IV-3. Phagocytosis was measured microscopically by counting ingested aggregated human IgG- or BSA-treated ox E (Eo'-IgG or Eo'-BSA). IFN-gamma increased the phagocytosis of Eo'-IgG but not that of Eo'-BSA, and PMA increased the phagocytosis of both Eo'-IgG and Eo'-BSA. Bt2cAMP decreased both basal and IFN-gamma- and PMA-augmented phagocytosis of U937 cells. Dexamethasone also inhibited both basal and IFN-gamma-augmented Fc gamma RI expression and PMA-augmented Fc gamma RII expression and phagocytosis, but did not affect IFN-gamma-augmented phagocytosis of Eo'-IgG. The augmentation of phagocytosis of Eo'-IgG by IFN-gamma thus seems to be due mainly to the increased internalizing process rather than to increased Fc gamma RI expression. TGF-beta slightly decreased Fc gamma R expression. In a study of the participation of protein kinase C (PK-C), it was found that H-7, a PK-C inhibitor, did not inhibit either IFN-gamma- or PMA-enhanced Fc gamma RI and Fc gamma RII expression, respectively, and 1-oleoyl-2-acetylglycerol and N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide, both PK-C activators, did not show any apparent increase in Fc gamma R expression and phagocytosis. These results show that Fc gamma RI and Fc gamma RII expression on U937 cells is regulated by different mechanisms and that IFN-gamma and PMA play their roles in Fc gamma R expression and phagocytosis by different pathways. It is possible that cAMP but not PK-C plays an important role in the regulation of Fc gamma R expression and phagocytosis.