Characteristics of private-sector managed care for mental health and substance abuse treatment.

Objective: This study examined diversity during the late 1980s in managed care programs for mental health, alcohol abuse, and drug abuse to identify ways in which research can generate more meaningful data on the effectiveness of utilization review programs.

Methods: Telephone interviews were conducted with representatives of utilization review programs for employee health insurance plans in 31 firms that employed 2.1 million people in 1990.

Studies on antigen binding by intact and hinge-deleted chimeric antibodies.

A matched set of chimeric IgG1 and IgG4 antibodies were used to investigate the role of the IgG hinge in binding to Ag with differing space between the epitopes. Antibodies bearing identical V regions and either IgG1 or IgG4 C regions were engineered with and without hinges. We measured the binding of these antibodies to the peptide CYYYEEEEY and to CYYYEEEEY-BSA conjugates with decreasing numbers of peptides per BSA molecule.

Effect of H chain V region on complement activation by immobilized immune complexes.

Activation of C by immune complexes (IC) in tissues and the inflammatory consequences are major determinants in the pathogenesis of many autoimmune disorders. To assess the factors involved in C activation by such IC, we examined the binding of C components by chimeric IgG1 antibodies bound to immobilized Ag. We previously reported that alterations in the H chain V regions can affect the binding of first component of C (C1q) and a major breakdown product of the third C component (C3b) when otherwise identical antibodies were bound to immobilized (Tyr, Glu)-Ala-Lys.

Variable region differences affect antibody binding to immobilized but not soluble antigen.

We have examined the antigen binding characteristics of two chimeric IgG1 antibodies that differ only in the heavy chain variable region. Antibodies 10B and B11 were expressed from two different anti-(Tyr,Glu)-Ala-Lys murine VH genes joined to human IgG1 constant region genes in a murine anti-(Tyr,Glu)-Ala-Lys heavy chain loss variant hybridoma. The binding characteristics of the antibodies to (Tyr,Glu)-Ala-Lys and to a peptide conjugate, CYYYEEEEY:BSA, were measured in solution and solid phase assays.

Alteration in H chain V region affects complement activation by chimeric antibodies.

Chimeric antibodies to the synthetic polypeptide (Tyr, Glu)-Ala-Lys ((T,G)-A-L) were used to examine C activation by human IgG1. Two IgG1 antibodies, which contained mouse L chains and H chains with mouse V domains and human C domains, differed only in their VH domain. Ag binding and C activation by these antibodies were analyzed by ELISA.

Binding of double-stranded DNA to glomeruli of rats in vivo.

In vivo binding of double-stranded DNA (dsDNA) to renal glomeruli of rats was examined. 125I-dsDNA (600 basepairs) was perfused with 131I-IgG as a blood marker into the right renal artery of normal rats, and blood flow was restored. After 10 minutes, isolated glomeruli showed a specific uptake of DNA, which increased in a saturable fashion with increasing doses of administered DNA.

Inpatient and outpatient psychiatric services: substitutes or complements?

Patients at risk for psychiatric hospitalization make only limited use of outpatient services, although clinical research has demonstrated that outpatient treatments and home care can be as effective as inpatient psychiatric treatment in treating certain mental health problems. The substitution of ambulatory services for inpatient care has in part been limited because insurers have restricted outpatient mental health benefits to control utilization. The authors critically review evidence from the economic and clinical literatures to determine the extent to which outpatient psychiatric treatment substitutes or complements inpatient treatment.

Complement fixation by small, DNase-resistant DNA-anti-DNA immune complexes.

125I-ds DNA-anti-DNA immune complexes (IC) formed at antibody excess and containing DNA of 300-350 base pairs (bp) fixed complement, incorporated C3b and bound to the C3b receptors (CR1) on human red blood cells (RBC). When the IC were treated with DNase to generate small, DNase-resistant IC, some of the IC incorporated C3b, but did not bind to RBC. In order to examine C3b incorporation and RBC binding by IC of specific sizes, the DNase treated IC were fractionated by sucrose density gradient (SDG) ultracentrifugation.

The reporting of stigmatizing health conditions: a comparison of proxy and self-reporting.

Previous studies have found that self-respondents tend to report a greater number of health problems than do household proxies. It has not been clear, however, if such results indicate reporting bias or reflect underlying health differences in the self-respondent and household proxy populations. Verification data from a survey of medical providers were examined in conjunction with the results of a national household survey.

The demand for ambulatory mental health services from specialty providers.

A two-part model is used to examine the demand for ambulatory mental health services in the specialty sector. In the first equation, the probability of having a mental health visit is estimated. In the second part of the model, variations in levels of use expressed in terms of visits and expenditures are examined in turn, with each of these equations conditional on positive utilization of mental health services.

In vivo studies with the novel anticancer agent mitozolomide (NSC 353451) on Lewis lung carcinoma.

Mitozolomide is one of the most effective drugs against Lewis lung carcinoma in the mouse. Two IP doses of 40 mg/kg (days 6 and 15 after IM transplantation of 3LL) or four doses of 20 mg/kg given at various intervals (starting from day 6) increased survival time by 100%. A single IP dose of 80 mg/kg was toxic, and 10 mg/kg was ineffective even when this dose was given on eight occasions.

Specialty and general ambulatory mental health services. Comparison of utilization and expenditures.

A substantial amount of ambulatory mental health services are received outside of the specialty mental health sector; however, precise estimates are lacking. To determine national estimates of utilization and expenditures for total ambulatory mental health services, as well as separate estimates for the specialty mental health and general medical sectors, patterns of use were examined by standard demographic characteristics. Almost 5% of the US population in 1977 had at least one ambulatory visit in conjunction with a mental problem.

Antitumour imidazotetrazines--VIII. Uptake and decomposition of a novel antitumour agent mitozolomide (CCRG 81010; M and B 39565; NSC 353451) in TLX5 mouse lymphoma in vitro.

The uptake and incorporation of 8-carbamoyl-3-(2-chloroethyl)(6-14C-imidazo)[5,1-d]-1,2,3,5-tetrazin+ ++-4-(3H)- one (Mitozolomide) into TLX5 mouse lymphoma cells has been studied in vitro. Uptake was rapid, reaching a cell/medium distribution of approximately unity in 1 min at 37 degrees and 10 min at 4 degrees, directly proportional to drug concentration and was unaffected by metabolic inhibitors. These results are consistent with a simple diffusion mechanism.

Dynamics of interaction between complement-fixing antibody/dsDNA immune complexes and erythrocytes. In vitro studies and potential general applications to clinical immune complex testing.

Soluble antibody/3H-double-stranded PM2 DNA (dsDNA) immune complexes were briefly opsonized with complement and then allowed to bind to human erythrocytes (via complement receptors). The cells were washed and subsequently a volume of autologous blood in a variety of media was added, and the release of the bound immune complexes from the erythrocytes was studied as a function of temperature and time. After 1-2 h, the majority of the bound immune complexes were not released into the serum during blood clotting at either 37 degrees C or room temperature, but there was a considerably greater release of the immune complexes into the plasma of blood that was anticoagulated with EDTA.

Complement-component-C3-opsonized immunoglobulin G anti-DNA antibodies do not bind effectively to red blood cells unless aggregated on a high-Mr DNA matrix.

Large, soluble ds (double-stranded) DNA-IgG (immunoglobulin G) anti-dsDNA immune complexes (greater than or equal to 200 S) that were previously opsonized with complement were digested with DNAase. The small complement-component-C3-fragment-labelled IgG (11-14 S) that was then isolated did not bind effectively to complement receptor type 1 on human red blood cells. However, when this IgG was immune-complexed with 3H-labelled PM2 (bacteriophage directed against a marine Pseudomonas) dsDNA (Mr approximately 6 X 10(6), substantial binding of both the DNA antigen and IgG to the erythrocytes was demonstrable.

Suramin inhibits the binding of complement-fixing antibody/double-stranded DNA immune complexes to CR1.

The effects of varying concentrations of heparin and suramin on the complement-mediated binding of antibody/double-stranded DNA immune complexes to red blood cells (RBCs) and Raji cells have been investigated. If the immune complexes are briefly opsonized with complement, suramin can block binding to both cell types, and heparin can block binding to RBCs. In addition, if these complexes are first allowed to bind to RBCs or Raji cells, relatively brief incubations in suramin are sufficient to cause release of the complexes from the cells' C3b receptors.

Quantitative determination of anti-dsDNA antibodies and antibody/dsDNA stoichiometries in prepared, soluble complement-fixing antibody/dsDNA immune complexes.

We have investigated quantitatively the complement-mediated binding of prepared, soluble 125I-7S IgG antibody/3H-dsDNA immune complexes to human red blood cells (RBCs). We have performed these studies by using a detailed modification of the RBC-CF assay [Pedersen et al., J.

The kinetics of [3H]-dsDNA/anti-DNA immune complex formation, binding by red blood cells, and release into serum: effect of DNA molecular weight and conditions of antibody excess.

[3H]dsDNA/anti-DNA immune complexes (IC) formed, fixed complement, and bound rapidly to red blood cells (RBC) in whole blood (less than 5 min), but were released from the cells more slowly. The rate of release was dependent on both the antibody:DNA ratio and the m.w.

Quantitative analyses of complement fixation in three immune complex systems.

The quantitative interaction of three different immune complex systems with complement has been investigated. dsDNA/anti-DNA, heat-aggregated IgG subfractions, and human IgG/rabbit anti-human IgG complexes were tested for their ability to consume complement (immune haemolysis assay) and to bind to red blood cells in a complement-mediated reaction (the RBC-CF assay). Our results indicate that some physical and immunological properties of the dsDNA/anti-DNA immune complex systems are significantly different from those of immune complexes that involve more common globular protein antigens.

Antitumour imidazotetrazines--IV. An investigation into the mechanism of antitumour activity of a novel and potent antitumour agent, mitozolomide (CCRG 81010, M & B 39565; NSC 353451).

8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4-(3H )-one- mitozolomide (CCRG 81010, M & B 39565, NSC 353451) is a potent inhibitor of the growth of a number of experimental tumours and can potentially decompose to give either an isocyanate or the monochloroethyltriazene (MCTIC). In vitro CCRG 81010 is not cross-resistant with the bifunctional alkylating agents against the Walker carcinoma. To investigate the mechanism of the antitumour activity of CCRG 81010 a comparison has been made with BCNU and MCTIC on precursor incorporation into macromolecules in TLX5 mouse lymphoma cells.