Abstract. Two intracellular calcium-release channel proteins, the inositol trisphosphate (InsP3), and ryanodine receptors, have been identified in mammalian and avian cerebellar Purkinje neurons. In the present study, biochemical and immunological techniques were used to demonstrate that these proteins coexist in the same avian Purkinje neurons, where they have different intracellular distributions.Western analyses demonstrate that antibodies produced against the InsP3 and the ryanodine receptors do not cross-react.Based on their relative rates of sedimentation in continuous sucrose gradients and SDS-PAGE, the avian cerebellar InsP3 receptor has apparent native and subunit molecular weights of '~,1,000 and 260 kD, while those of the ryanodine receptors are ,~2,000 and 500 kD.Specific Both receptors appear to be more abundant at main branch points of the dendritic arbor. In Purkinje neuron cell bodies, both the InsP3 and ryanodine receptors are present in smooth and rough ER, subsurface membrane cisternae and to a lesser extent in the nuclear envelope. In some cases the receptors coexist in the same membranes. Neither protein is observed at the plasma membrane, Golgi complex or mitochondrial membranes.Both the InsP3 and ryanodine receptors are associated with intracellular membrane systems in axonal processes, although they are less abundant there than in dendrites.These data demonstrate that InsP3 and ryanodine receptors exist as unique proteins in the same Purkinje neuron. These calcium-release channels appear to coexist in ER membranes in most regions of the Purkinje neurons, but importantly they are differentially distributed in dendritic processes, with the dendritic spines containing only InsP3 receptors.

We studied 16 218 pregnant women from two income groups to determine the incidence of primary cytomegalovirus (CMV) infection and its consequences for the offspring. In the high-income group, 64.5% of the women were seronegative for CMV and 1.6% had primary CMV infection. In the low-income group, only 23.4% of the women were seronegative for CMV, but 3.7% experienced a primary infection. The rate of transmission in utero was similar in the two groups (39% and 31%). Congenital infections were more frequent in the low-income group; however, primary CMV accounted for 25% of the congenital infections in this group, in contrast to 63% of the high-income cases. Infections acquired early and late in gestation had similar rates of transmission in utero, but three infants (8%) with symptomatic congenital infection and five infants (13.5%) who have developed significant handicaps were exposed in the first half of pregnancy. Primary CMV infection during pregnancy poses a 30% to 40% risk of intrauterine transmission and adverse outcome is more likely when infection occurs within the first half of gestation.

No abstract

We studied the incidence of primary and recurrent cytomegalovirus infection in 3712 pregnant women--2698 of middle to high income and 1014 of low income--to determine whether there were differences in the effects on the fetus. In the higher-income group, 1203 women (45 per cent) did not have antibodies to cytomegalovirus and were therefore susceptible to primary infection, as compared with 179 women (18 per cent) of low income. Congenital infection occurred more often (1.6 vs. 0.6 per cent) in infants in the low-income group. In this group it was associated with recurrent maternal infection more often (in 82 per cent) than with primary maternal infection, whereas in the upper-income group, it was associated with primary maternal infection in half the cases. Altogether, there were 32 cases of congenital cytomegalovirus infection - 16 in each group. Whereas primary maternal infection resulted in fetal infection in only half the cases, it was more likely to ge associated with clinically apparent disease than was recurrent infection. When these cases were combined with 28 cases of congenital infection retrospectively identified at other prenatal clinics, five of 33 infected infants born after primary maternal infection had clinically apparent disease, as compared with none of 27 born after recurrent maternal infection. We conclude that congenital cytomegalovirus infection resulting from primary maternal infection is more likely to be serious than that resulting from recurrent infection, and is more likely to occur in upper socioeconomic groups.

19788 -19794). The current studies were undertaken to further examine the interactions between vitronectin and fibrin(ogen). Comparison of vitronectin levels in plasma with those in serum indicates that ϳ20% of plasma vitronectin is incorporated into the clot. When the time course of biotinylated-vitronectin incorporation into clots formed from 125 I-fibrinogen is monitored, vitronectin incorporation into the clot parallels that of fibrinogen in the absence or presence of activated factor XIII. Vitronectin binds specifically to fibrin matrices with an estimated K d of ϳ0.6 M. Additional vitronectin subunits are assembled on fibrin-bound vitronectin multimers through self-association. Confocal microscopy of fibrin clots reveals the globular vitronectin aggregates anchored at intervals along the fibrin fibrils. This periodicity raised the possibility that vitronectin interacts with the ␥A/␥ variant of fibrin(ogen) that represents about 10% of total fibrinogen. In support of this concept, the vitronectin which contaminates fibrinogen preparations co-purifies with the ␥A/␥ fibrinogen fraction, and clots formed from ␥A/␥ fibrinogen preferentially bind vitronectin. These studies reveal that vitronectin associates with fibrin during coagulation, and may thereby modulate hemostasis and inflammation.Vitronectin is a multifunctional plasma glycoprotein that participates in the regulation of coagulation, fibrinolysis, and the complement cascade (reviewed in Refs. 1 and 2). Vitronectin also regulates cell adhesion and pericellular proteolysis on surfaces of cells and extracellular matrices (1-5). Like fibrinogen, vitronectin is found in plasma at micromolar concentrations (6), and is stored in megakaryocyte and platelet ␣-granules (7-9). In plasma, vitronectin circulates as a native, monomeric form that is a mixture of 72-kDa single-chain and two-chain disulfide-linked species (10 -12). Under normal conditions, less than 3% of plasma vitronectin is comprised of more reactive oligomeric forms that display enhanced affinity for heparin or heparin-like molecules, and for the conformationsensitive monoclonal antibody 8E6 (10 -12).During acute phase response, plasma vitronectin levels increase (6), with a relative increase in the percentage of oligomeric vitronectin (13). Levels of the oligomeric forms of vitronectin in serum relative to plasma also increase; indicating the process of coagulation alters vitronectin structure and function (10 -12, 14). The altered, oligomeric form of vitronectin is generated, at least in part, by interactions with other plasma proteins such as thrombin-antithrombin complexes (11, 12, 14, 15, and complement C5b-9 complexes (11, 12, 16).A portion of vitronectin in plasma (17,18), and in platelets is complexed with type 1 plasminogen activator inhibitor (PAI-1) 1 (8,9,19), an interaction that induces the formation of higher order complexes (4,5,20,21) and influences the structure and function of both PAI-1 and vitronectin. Thus, when bound to vitronectin, PAI-1 is stabilized in its active conforma...