Explaining Male Sex Offender Recidivism: Accounting for Differences in Correctional Supervision.

PURPOSE: Contrary to public opinion, empirical studies have consistently shown that persons convicted of a sexual offense (PCSO) are less likely to recidivate with a general offense. While researchers often point toward the surreptitiousness of sexual offending to explain low rates of recidivism, this paper tests a novel explanation: SOs recidivate at lower rates than persons convicted of a non-sexual offense (PCNSO) because they are more often revoked to prison before they are able to commit a new crime, perhaps owing to more restrictive post-release supervision guidelines. METHODS: Using a sample of 196,468 unique male releases, the difference in general and sexual recidivism between PCSO (n = 29,420) and PCNSO was assessed through survival analyses (Cox regression models). RESULTS: Results demonstrated that PCSO were significantly less likely to be reconvicted for a general crime, but more likely for a sex offense. They were also more likely to be reincarcerated due to a revocation without a new sentence. Accounting for revocations, the difference in reconviction risk lessens between the groups but does not disappear. CONCLUSIONS: This analysis provides evidence that differences in community supervision are contributing to the difference in recidivism rates between PCSO and PCNSO. Implications and future research are discussed.

Vitamin D binding protein sequesters monomeric actin in the circulation of the rat.

Plasma vitamin D binding protein (DBP) may scavenge actin released during cell lysis. We examined the plasma disappearance and tissue appearance of 125I-DBP, 125I-G-actin, and the DBP-G-actin complex after their intravenous administration to rats. The plasma disappearance of DBP and DBP-actin were indistinguishable, with rapid initial (t1/2 = 2.6 h) and slower second (t1/2 = 7 h) slopes. After 125I-G-actin (nanomole) injection, plasma disappearance paralleled that of DBP and DBP-actin. All injected actin was associated with DBP, without evidence of free actin, actin-gelsolin complexes or actin oligomers. Tissue appearances of 125I-apo-DBP (apo) or holo-DBP were similar, with highest accumulations in perfused liver, kidney, and skeletal muscle. Although more complex phenomena (plasma entry of F-actin and intracellular actin binding proteins) would occur in vivo after cell lysis, our results suggest a role for DBP in the sequestration and disposition of actin monomers in the circulation.

Characterization of a monoclonal antibody to human serum vitamin D binding protein (Gc globulin): recognition of an epitope hidden in membranes of circulating monocytes.

We have developed a murine hybridoma cell line that secretes a monoclonal antibody directed to the serum human vitamin D binding protein (hDBP), a 58,000-dalton alpha-globulin with a high avidity for 25-hydroxycholecalciferol and globular actin. This immunoglobulin G1 kappa-light chain antibody was produced by the fusion of the spleen cells from BALB/c mice, immunized with purified hDBP, with SP2/0-AG4 myeloma cells. The antibody was easily removed from the supernatant of hybridoma cultures or mouse ascites fluid by Protein A affinity chromatography. Apparent serum monospecificity was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing gels transblotted to nylon membranes and overlayed with purified MAK 89 antibody and radioiodinated Protein A. The affinity of the antibody is high [dissociation constant (Kd) = 2.6 X 10(-11) M]. Parallel displacement of tracer by hDBP and human serum was observed. The sera from various species displaced the hDBP tracer in the following potency: monkey more than cat more than dog more than guinea pig. RIAs for DBP from several species are feasible with this antibody. This antibody does not, in contrast to polyclonal anti-hDBP antiserum, bind to viable monocytes. However, the MAK 89 antibody does bind to the membranes of well washed, fixed, and permeant circulating monocytes. Surface membrane radioiodination of monocytes and immunoprecipitation of the detergent lysates with the antibody demonstrates a protein with molecular weight equivalent to hDBP. The epitope recognized, therefore, appears to be hidden in the viable cells, suggesting an intimate and intricate association of the hDBP and monocyte plasma membrane.

Detection of vitamin D binding protein on the surface of cytotrophoblasts isolated from human placentae.

Vitamin D binding protein (DBP), a Mr 56,000-58,000 alpha 2-glycoprotein, is the major serum protein involved in the transport of vitamin D sterols. Recently it has been suggested that DBP may also be involved in immunoglobulin G binding to cells. Because the trophoblast is involved in the transport of molecules such as vitamin D and immunoglobulin G to the fetus, we asked whether DBP could be detected on the surface of human placental trophoblast cells. Cytotrophoblasts purified from human term placentae were fixed and made permeant with Triton X-100 and examined by indirect immunofluorescence after incubation with a monoclonal antibody to DBP. Greater than 90% of these cells stained positively, whereas no staining was observed with nonimmune antiserum. The presence of DBP on/in the surface of cytotrophoblasts could also be demonstrated by fluorescent cytometry. When cell surface-associated proteins of cytotrophoblasts were radioiodinated, a Mr 57,000 radiolabeled protein could be immunoisolated from the cell lysate with a purified monospecific polyclonal antibody to DBP. Immunoisolation of this radiolabeled protein was prevented by the addition of excess unlabeled human DBP to the cell lysate before incubation with antibody. This Mr 57,000 radiolabeled protein could also be isolated by affinity chromatography selecting for proteins that bind to globular actin. When cytotrophoblasts were incubated with [35S]methionine for 3 or 18 h, active synthesis of DBP could not be demonstrated by immunoisolation techniques. These studies demonstrate the presence of DBP on the surface of well washed, human cytotrophoblasts. This DBP may be maternally derived, since active synthesis of DBP could not be demonstrated.

Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein.

We measured the free fraction of 25-hydroxyvitamin D (25OHD) in human serum and determined that 25OHD bound to a component with an affinity constant of 7 X 10(8) M-1 and a concentration of 4.5 X 10(-6) M. This concentration was equal to that of the vitamin D-binding protein (DBP) in the same serum sample. We removed DBP from the serum using actin affinity columns and found that the affinity for 25OHD of the remaining serum components was equivalent to that of human serum albumin (6 X 10(5) M-1). We then measured the free fractions of 25OHD, DBP, and albumin in normal and cirrhotic subjects. We calculated that 88 +/- 3% (+/- SD) and 83 +/- 8% of the 25OHD were bound to DBP in the serum of normal and cirrhotic subjects, respectively. We compared previously reported data for the free fraction and the free concentration of 1,25-dihydroxyvitamin D in these subjects with the current data for the free fraction and free concentration of 25OHD. The total concentrations and free fractions of both metabolites correlated to each other and to the DBP and albumin concentrations in these subjects, but the free concentrations of these metabolites did not. We conclude that 25OHD, like 1,25-dihydroxyvitamin D, is transported in blood bound primarily to DBP and albumin. Changes in the concentrations of DBP and albumin affected the total and free fractions of 25OHD in serum, but the actual free concentration of 25OHD was independent of such changes.

Pathogenesis of hypercalcemia in lymphosarcoma cell leukemia. Role of an osteoclast activating factor-like substance and a mechanism of action for glucocorticoid therapy.

The pathogenesis of hypercalcemia and mode of action of glucocorticoid therapy was examined in a patient with lymphosarcoma cell leukemia. Circulating neoplastic cells were cultured in vitro and secreted a bone-resorbing factor. The bone-resorbing factor was partially purified with the use of a bioassay for bone resorption, and was found to be chromatographically and pharmacologically similar to osteoclast activiating factor (OAF), which is produced by normal mitogen-activated peripheral blood lymphocytes. Other factors which stimulate bone resorption, such as parathyroid hormone, prostaglandins and the vitamin D metabolites, were excluded by criteria which included dose-response curves, radioimmunoassays, extraction in organic solvents and failure of glucocorticoids to inhibit bone-resorbing activity. The patient's hypercalcemia responded rapidly to prednisone therapy. The effects of the bone-resorbing factor secreted by the neoplastic cells on bone cultures to which cortisol was added were examined. Cortisol inhibited bone resorption directly at low doses (10(-8) M), which suggests that prednisone may have lowered the serum calcium in this patient by direct inhibition of bone resorption.

Identification of a subset of group B donors reactive with monoclonal anti-A reagent.

Two red blood cell (RBC) units labeled group B were returned to the source blood center after they had been retyped as AB by a transfusion service. The discrepancy could be reproduced, but only with the use of the transfusion service's reagent, Ortho Diagnostic's anti-A Bioclone (a licensed, blended, murine monoclonal anti-A reagent). RBCs from 35 of 3,458 random group B donors (1%) reacted with the monoclonal anti-A after immediate centrifugation. Reactivity was associated with high serum levels of B-gene-specified transferase and was caused by the MH04 component, a potent anti-A capable of detecting some examples of Ax RBCs. It is probable that the potency of MH04 permitted detection of low levels of A determinants synthesized by the donors' unusually strong B-gene-specified transferase. Transfer of N-acetylgalactosamine by B-gene-specified transferases, reported in vitro, has not been detected previously in vivo. Use of highly sensitive monoclonal reagents may result in clinically ambiguous blood grouping results.

Endoscopic brush cytology and biopsy in the diagnosis of cancer of the upper gastrointestinal tract.

Brush cytology and biopsy under direct vision was performed on 250 patients. Of the 44 proven cases with cancers of the upper gastrointestinal tract, brush cytology yielded positive results in 88.6%, and multiple mucosal biopsies yielded positive results in 93.2%. With the combined technique the results increased to 95.4%. False-negative results were due to large tumors with necrotic surfaces or to infiltrative tumors at the cardioesophageal junction. There was one false positive with brush cytology and none with biopsy. Four cases of early gastric cancer were diagnosed with the combined technique.

Characterization of the human plasma binding protein for vitamin D and its metabolites synthesized by the human hepatoma-derived cell line, Hep 3B.

Screening of three human hepatoma-derived cell lines revealed the presence of an immunologically similar plasma binding protein for vitamin D and its metabolites in media from Hep 3B cells. Approximately 3% of protein synthesized and secreted by these cells was immunoprecipitated by specific antiserum to the D-binding protein. Medium content of the protein increased over 11 days following cell seeding, and negligible amounts of 125I-labeled binding protein added to cultures were degraded over 48 h. The hepatoma-derived binding protein was indistinguishable from plasma binding protein or reference pure protein in gel filtration, sucrose gradient ultracentrifugation, and polyacrylamide gel electrophoresis systems. The Hep 3B cell product was found to bind mole/mol with monomeric actin, and bind vitamin D sterols with an affinity and specificity characteristic of the human plasma binding protein. The findings argue strongly for the identity of the Hep 3B cell product and the human plasma protein. The continuous availability of the Hep 3B cell line provides a reasonable model for investigations of biosynthesis and release of this important plasma protein.

Actin affinity chromatography in the purification of human, avian and other mammalian plasma proteins binding vitamin D and its metabolites (Gc globulins).

The human plasma protein binding vitamin D and its metabolites (Gc globulin; group-specific component) has been isolated from human plasma by column affinity chromatography on gels to which monomeric actin was covalently attached. Rabbit skeletal-muscle G-actin was covalently coupled to amino-agarose gels before the application of human plasma. At actin/protein molar ratios of 4-8:1, excellent recovery (approximately 58%) of purified binding protein was achieved. After 0.75 M-NaCl washes, the binding protein was eluted from the columns in 3 M-guanidinium chloride, dialysed and analysed. These eluates contained the binding protein as 34-100% of the total protein, reflecting a 130-fold average purification in this single step. In the presence of Ca2+, gelsolin (another plasma protein that binds actin) was apparently retained by the affinity column, but this was prevented by chelation of plasma Ca2+. The actin affinity step also was effective in the isolation of the binding protein from rat, rabbit and chicken plasma, as indicated by autoradiographs of purified fractions analysed by gel electrophoresis after incubation with 25-hydroxy[26,27-3H]cholecalciferol. Further isolation by hydroxyapatite chromatography yielded a purified binding protein which displayed characteristic binding activity toward vitamin D metabolites and G-actin, and retained its physicochemical features. This brief purification sequence is relatively simple and efficient, and should prove to be useful to investigators studying this interesting plasma protein.

Effects of glucocorticoids on osteoclast-activating factor.

Glucocorticoids lower the serum calcium in patients with hypercalcemia due to myeloma and related lymphoproliferative disorders. OAF is a potent bone-resorbing lymphokine which is probably responsible for the bone lesions and hypercalcemia which occur in patients with these hematological neoplasms. In this study, we have examined the effects of cortisol on the production of OAF and its biological activity in order to clarify the mechanism of action of glucocorticoids in lowering the serum calcium in these disorders. The effects of OAF-containing media on bone resorption were inhibited by cortisol at concentrations from 10-5M to 10-9M. In contrast, OAF production was not inhibited by cortisol at concentrations less than 10-5M. These data support the hypothesis that glucocorticoids inhibit the effects of OAF in vivo primarily by a direct effect on bone resorption.

Selective, rapid removal of the vitamin D-binding protein and its sterol ligands from human and bovine plasma.

Rapid and selective removal of plasma vitamin D-binding protein was effected by the serial passage of plasma over four columns of agarose containing covalently linked skeletal muscle G-actin. By maintaining an actin-to-binding protein molar ratio of at least 4 to 1 throughout, greater than 99% of the binding protein was removed from the fourth column's eluate. In contrast, 87% of the total plasma or serum protein applied was recovered, and electrophoretic analyses of human and bovine sera that had undergone these affinity chromatography steps revealed no major alterations in protein distribution. The procedure also removes vitamin D sterols selectively, with preference for 25-hydroxycalciferol (90% removal) over 1,25-dihydroxycalciferol (65-70% removal) and calciferol (70% removal), in accordance with the known affinity displayed by the binding protein for these sterol ligands. Recovery of other serum constituents (cortisol, proteins, peptide hormones, calcium and alkaline phosphatase) was excellent, further confirming the selectivity of the technique. Utilizing vitamin D-deficient serum, serum depleted of the vitamin D-binding protein was not distinguishable from control serum in supporting the growth of human fibroblasts in vitro. In comparison with other methods to remove serum-binding protein or sterols, the present technique is more selective and can be used for mammalian and avian sera. Material so prepared could prove useful for studies of the cellular access, metabolism, and effects of vitamin D sterols in vitro.

Ontogenesis of the rabbit intestinal receptor for 1,25-dihydroxyvitamin D3--evidence for increased receptor content during late suckling and lactating periods.

The 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) intestinal receptor was not detected in term fetal rabbits. This receptor was present at 2 weeks postpartum and its concentration reached a maximum at 4 weeks of age, and declined to adult levels by 10 weeks postpartum. The 1,25(OH)2D3 intestinal receptor concentration was elevated at 2 weeks postpartum in lactating rabbits, but returned to normal adult concentrations by 4 weeks postpartum. In rabbits of various ages, only minor changes in the equilibrium dissociation constant of this receptor were observed. These data indicate that increasing the small intestine 1,25(OH)2D3 receptor concentration is one mechanism by which the rabbit adapts to periods of increased calcium demand.

Vitamin D3 binding protein required for in vitro activation of macrophages after alkylglycerol treatment of mouse peritoneal cells.

In vitro treatment of peritoneal cells with dodecylglycerol (DDG) in 10% foetal calf serum (FCS) supplemented medium RPMI-1640 results in a greatly enhanced Fc receptor-mediated phagocytic activity of macrophages. This macrophage activation process requires a serum factor in the alpha 2-globulin fraction. When mouse peritoneal cells were treated with 50 ng DDG/ml in a serum-free 0.1% egg albumin-supplemented medium RPMI-1640 (EA medium) for 30 min and cultured in EA medium containing electrophoretically fractionated alpha 2-globulin for 3 hr, a markedly enhanced activation of macrophages was observed. To improve fractionation of alpha 2-globulin, FCS was first precipitated with 50% saturated ammonium sulphate and then the supernatant electrophoretically fractionated. The resultant alpha 2-globulin fraction was unable to support activation of macrophages. Vitamin D3 binding protein (DBP) of the alpha 2-globulin fraction is known to be precipitable by 50% saturated ammonium sulphate. When human alpha 2-globulin was treated with antiserum against human DBP and used in a medium for cultivation of DDG-treated peritoneal cells, no significant activation of macrophages was observed. Cultivation of DDG-treated peritoneal cells in a medium containing a low concentration of purified human DBP (group specific component, Gc) produced a greatly enhanced ingestion activity of macrophages. Purified human Gc protein, when used in an EA medium for step-wise cultivation of DDG-treated B and untreated T cells, was efficiently converted to a macrophage-activating factor.

Interactions among serum vitamin D binding protein, monomeric actin, profilin, and profilactin.

Human serum vitamin D binding protein (hDBP), a 58-kDa inter-alpha-globulin, is known to bind, monomeric actin (G-actin) in equimolar quantities. Using monoclonal and polyclonal anti-hDBP antibodies, hDBP, and radioiodinated actin, we developed a reliable saturation assay for actin bound to hDBP. By utilizing this assay, kinetic analysis, and ultracentrifugal sedimentation in sucrose gradients, these proteins' binding affinities (Kd = 10(-9) M) were demonstrated to be 10- to 100-fold greater than earlier estimates. At 4 degrees C, hDBP has an association rate constant of 2.2 x 10(4) M-1 s-1 and a rate of dissociation displaying a t1/2 of 22 h. This high affinity binding was largely unaffected by conditions favoring actin filament formation (1 mM MgCl2 and/or 50 mM KCl), by the range of pH from 6.8 to 8.6 or by temperatures from 4 to 37 degrees C. Compared with ATP-alpha-actin, a 2-fold decrease of binding affinity was observed for the nonmuscle isoactins (beta,gamma), ADP-G-alpha-actin, and N'-ethylmaleimide-modified G-alpha-actin. The 25-hydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3 holo-sterol forms of hDBP bound actin in a manner indistinguishable from the apo-sterol hDBP. The common polymorphisms of hDBP (DBP1 slow, DBP1 fast, and DBP2) were shown to have an equal avidity for G-actin binding. Human platelet profilin competed with hDBP for binding to G-actin, but was 1000-fold less potent (Ki = 1.9 microM). When platelet profilactin was incubated with hDBP, profilin was liberated and hDBP-actin complexes formed. DNase I, which forms a triprotein complex with hDBP-G actin, did not alter the affinity of binding of actin by hDBP. The very high affinity binding observed, which was largely unaffected by the state of G-actin, pH, and ionic conditions, appears to support a constitutive role for plasma DBP in the sequestration of actin monomers, as well as actin from actin-profilin complexes, that are liberated during cell injury.

Identification of the sterol- and actin-binding domains of plasma vitamin D binding protein (Gc-globulin).

The mammalian plasma vitamin D binding protein (DBP), or Gc-globulin, is recognized to have at least two functional properties: sterol binding and G-actin sequestration. Affinity labeling of the sterol binding site with the radioactive electrophilic ligand, 3 beta-(bromoacetoxy)-25-hydroxycholecalciferol, followed by limited proteolysis, permitted the isolation and identification of three overlapping peptides in the amino terminus of the molecule. When G-actin affinity chromatography was applied to other proteolytic fragments, two fragments from the carboxy terminus of the molecule were isolated and identified. Another, large, tryptic fragment displayed both sterol- and actin-binding properties. The amino-terminal assignment of the sterol-binding domain was confirmed by demonstrating sterol-specific binding by an in vitro transcribed and translated product of a mutated rat DBP cDNA encoding a protein truncated in its carboxy terminus. The sterol-binding domain was localized to the region between the first-amino-terminal disulfide bond, and the actin-binding domain was found between residues 350 and 403. A high degree of sequence conservation in these regions was found among human, rat, and mouse DBP's. These functional domain assignments confirm the apparent independence of these two binding activities and help to explain the observed triprotein complex of DBP-actin-DNase I and the competition between DBP and profilin for G-actin binding. Our findings should facilitate more precise delineation of the binding domains by site-directed mutagenesis experiments.

Hemolytic transfusion reaction due to anti-Tc(a).

BACKGROUND: Anti-Tc(a) detects a high-incidence antigen in the Cromer blood group system. Cromer system antibodies have not usually been associated with hemolytic transfusion reactions or hemolytic disease of the newborn. CASE REPORT: Anti-Tc(a) (initially identified in the patient's serum in 1982) was not detected when she was admitted to the hospital with upper gastrointestinal. bleeding. Three units of red cells were administered. The patient was discharged, but was readmitted to the hospital after her hemoglobin fell to 7.1 g per dL. Antibody detection tests remained negative and three additional units were transfused. Over the next 7 days, her hemoglobin steadily fell to 5.5 g per dL. The level of lactate dehydrogenase rose to 1257, the plasma hemoglobin rose to >16 mg per dL, and the haptoglobin decreased to <6 mg per dL. Five days after transfusion, her direct antiglobulin test was weakly reactive with complement-specific antiglobulin reagents. Eluates were nonreactive. Anti-Tc(a) was detected in her serum; no other antibodies were detected. Differential typing failed to detect any circulating Tc(a+) red cells. The antibody was strongly reactive in a monocyte monolayer assay. CONCLUSION: Although Cromer system antibodies have generally not been proven to be clinically significant in transfusion therapy, the destruction of red cells from six units of transfused Tc(a+) red cells in this patient indicates that anti-Tc(a) may have destructive potential in some patients.

Disruption of microfilament organization in living nonmuscle cells by microinjection of plasma vitamin D-binding protein or DNase I.

Plasma vitamin D-binding protein (DBP), which binds to monomeric actin, causes the breakdown of stress fibers when it is microinjected into nonmuscle cells. Disruption of the stress fiber network is also accompanied by shape changes in the cell that resemble those seen after cytochalasin treatment. When DBP was coinjected with fluorescently labeled alpha-actinin, no fluorescent stress fibers or attachment plaques were visible 30 min after injection. Twelve hours later the cells regained their flattened shape and their stress fibers. Fluorescently labeled DBP causes the same reversible changes in cell shape as the unlabeled protein. Upon injection, the labeled DBP diffuses throughout the cytoplasm, becoming localized by 12 hr in a punctate pattern, presumably due to lysozomal sequestration. Similar injections of DBP into skeletal myotubes and cardiac myocytes did not lead to shape changes or breakdown of nascent and/or fully formed myofibrils, even though DBP has a 2-fold higher binding affinity for muscle actin over that of the nonmuscle isoactins. Similar differential effects in nonmuscle cells were also observed after the microinjection of DNase I, another protein capable of binding monomer actin. The effects of these microinjected monomer actin-binding proteins imply that an accessible pool of monomer actin is needed to maintain stress fiber integrity in nonmuscle cells but not the integrity of the nascent or fully formed myofibrils in muscle cells.