Ten adaptive strategies for family and work balance: advice from successful families.

Despite negative media images and social dynamics insensitive to the lives of many dual-career couples, research shows that these families are largely healthy and thriving. In this study, we investigated the adaptive strategies of middle-class, dual-earner couples (N = 47) with children that are successfully managing family and work. Guided by grounded-theory methodology, analysis of interview data revealed that these successful couples structured their lives around 10 major strategies: Valuing family, striving for partnership, deriving meaning from work, maintaining work boundaries, focusing and producing at work, taking pride in dual earning, prioritizing family fun, living simply, making decisions proactively, and valuing time. Each adaptive strategy is defined and illustrated through the participants' own words. Clinical applications for therapists working with dual-earner couples are offered.

AAMFT Master Series tapes: an analysis of the inclusion of feminist principles into family therapy practice.

Content analysis of 23 American Association for Marriage and Family Therapy Master Series tapes was used to determine how well feminist behaviors have been incorporated into "ideal" family therapy practice. Feminist behaviors were infrequent, being evident in fewer than 3% of time blocks in event sampling and 10 of 39 feminist behaviors of the Feminist Family Therapist Behavior Checklist. These eminent therapists most often dealt with empowerment of male clients and management of power differentials in the therapeutic relationship in a relatively feminist manner, but they tended to hold women responsible for family issues, endorsed traditional rather than egalitarian relationships, and overlooked how the social context affects families. Several of the therapists were blatantly sexist in their treatment of female clients, communicating disrespect of and pathologizing them. The few tapes portraying effective incorporation of feminist principles in family therapy indicate that a handful of behaviors are key to this approach.

A feminist analysis of self-help bestsellers for improving relationships: a decade review.

Self-help literature is pervasive and influential in the United States. A critical analysis of self-help books would help therapists to determine their utility for the therapeutic process and assist them in making reading recommendations to clients. In this study, a content analysis was conducted of the top 11 relationship self-help books on the New York Times Bestseller List over a period of 10 years (1988-1998) to determine the degree to which these books support a feminist approach to therapy. This study yielded three major findings. First, the number of feminist books, the number of nonfeminist books, and those falling in the middle across four components of feminist family therapy are about equal. However, the second major finding was that the top-selling books are more likely to be nonfeminist than feminist. The third finding is that most best-selling self-help books appear to have become less compatible with a feminist approach to relationships over time. This analysis encourages therapists to think critically about these best-selling books; it will also allow therapists to consider this methodology as a model for critically analyzing other books that they recommend to clients or use in their own professional development.

Mars and Venus: unequal planets.

Self-help books, a pervasive and influential aspect of society, can have a beneficial or detrimental effect on the therapeutic process. This article describes a thematic analysis and feminist critique of the best-selling self-help book, Men are from Mars, Women are from Venus. This analysis revealed that the author's materials are inconsistent with significant family therapy research findings and key principles of feminist theories. His descriptions of each gender and his recommendations for improving relationships serve to endorse and encourage power differentials between women and men.

The Power Equity Guide: attending to gender in family therapy.

In the past two decades, feminist scholars have challenged the field of family therapy to incorporate the organizing principle of gender in its theory, practice, and training. In this paper, we introduce a training, research, and therapeutic tool that provides guidance for addressing or observing gender and power differentials in the practice of family therapy. As a training tool, the Power Equity Guide helps trainees to translate their theoretical understanding of feminist principles into specific behaviors in therapy. Researchers and supervisors can use the Power Equity Guide to evaluate the practice of gender-informed family therapy. We also provide specific suggestions for its use by trainers, supervisors, therapists, and researchers.

Marriage and family consultation with ranch and farm families: an empirical family case study.

There is a paucity of marriage and family therapy literature addressing therapeutic consultation with farm and ranch families. This article describes a case study in which several Marital and Family Therapy approaches were used to consult with a ranch family. It also provides empirical data showing in which of five treatment phases changes occurred. Two generations, including four couples from an extended family, participated in family consultation over 42 months and completed assessments six times. Statistical results and clinical impressions confirm that the five-phase consultative process resulted in significant improvements in family satisfaction with adaptability and family strains levels and positive movement in seven other areas.

Are goals and topics influenced by gender and modality in the initial marriage and family therapy session?

Establishment of a goal is crucial to therapy, but identification of therapeutic goals may be difficult in conjoint therapy because each participant may identify a different problem. We examined the influence of gender on ability to successfully introduce therapeutic topics in marital and family therapy by conducting two studies. The first study evaluates the ability of therapists to identify therapeutic goals that matched goals prioritized by both women and men clients on pretherapy questionnaires. The second study examines the process of initial therapy sessions to see whether gender influences a client's ability to introduce a therapeutic topic. Results suggest that therapeutic topic is influenced by the interaction of gender and treatment modality. Specifically, therapists were better able to match women's pretherapy stated goals in marital therapy than family therapy, men were more successful at introducing topics in family therapy, and women were more successful at introducing topics in marital therapy.

Synthetic peptides inhibit the interaction of von Willebrand factor-platelet membrane glycoproteins.

We synthesized peptides of the general formula Argn, Lysn, and (Lys-Arg)n. These agents inhibited the ristocetin-mediated binding of vWF to GPIb and the binding of asialo-vWF to platelets. This inhibitory activity was proportional to the number of lysine and/or arginine residues/molecules present. Peptides to which the sequence of Arg-Gly-Asp-Val (RGDV) had been added at the carboxy-terminus of (Lys-Arg)n, Lysn, or Argn also inhibited vWF binding. Peptides with an RGDV sequence were found to block the binding of 125I-fibrinogen to ADP-stimulated platelets. These findings indicate that the general formulae (Lys-Arg)n, Lysn, and Argn with an RGDV sequence inhibit the binding of fibrinogen to activated platelets as well as the binding of vWF to GPIb. Thus, these peptides may behave as bifunctional antiplatelet agents.

[Further evaluation of GPIb binding domain of vWf by synthetic peptides].

We have already demonstrated that the GPIb binding domain of vWf resided at the regions corresponding to residues 474-488(G10) and 694-708(D5). Moreover, conformational change of vWf was suggested to be important for binding to GPIb. The effect of newly synthetized peptide combining G10 and D5 with lysin(G10-D5) on vWf binding to GPIb and platelet aggregation was studied. All synthetic peptides inhibited both vWf binding to GPIb, ristocetin-induced platelet aggregation and asialo vWf-induced platelet aggregation. G10-D5 possessed the most potent inhibitory activity in the interaction of vWf with GPIb. Only G10-D5 reacted with NMC-4 which recognized the epitope in appropriate conformation of vWf. These results indicate that G10-D5 retains some conformational structure and might be a good tool for anti-thrombotic agent.

Proteolysis of von Willebrand factor after thrombolytic therapy in patients with acute myocardial infarction.

In 20 patients with acute myocardial infarction (AMI) treated with streptokinase (SK, n = 7), recombinant single-chain tissue plasminogen activator (rt-PA, n = 7) or urokinase (UK, n = 6), the behavior of plasma von Willebrand factor (vWF) was studied before and 1.5, 3, 24, 48, and 72 hours after beginning thrombolytic therapy. vWF antigen (vWF:Ag) was high in plasma, especially after SK. The ristocetin cofactor (RiCof) activity of vWF, high before therapy, tended to decrease soon after therapy. This pattern of vWF changes was paralleled by the early loss of higher molecular weight multimers. By immunoblotting of immunopurified and reduced vWF and monoclonal antibody epitope mapping, we found that vWF was degraded after thrombolysis, especially after SK, as indicated by the higher values of two plasmin-generated fragments of 176 and 145 Kd. There were more plasmin-generated fragments in the five patients who had bleeding complications than in the remaining 15 who did not. In conclusion, quantitative and qualitative changes of vWF compatible with proteolytic degradation of the protein occur during thrombolytic therapy. Such degradation, roughly proportional to the degree of the general lytic state induced by each agent, might be a cofactor of the bleeding complications occurring in treated patients.

Fine mapping of monoclonal antibody epitopes on human von Willebrand factor using a recombinant peptide library.

A recombinant human von Willebrand factor (vWF) cDNA fragment library was constructed in lambda gt11 for the localization of anti-vWF monoclonal antibody epitopes. Twelve of 21 monoclonal antibodies screened identified epitopes expressed in lambda gt11 as beta-galactosidase fusion proteins. By sequence analysis, these antigenic determinants were localized to segments ranging from 17 to 105 amino acids in length. Four epitopes apparently shared by more than one antibody were identified, suggesting the presence of immuno-dominant epitopes within vWF. Monoclonal antibody C3, which blocks factor VIII (FVIII) binding to vWF, bound to the same epitope previously identified by a second monoclonal antibody which also blocks this function, suggesting that this region may be at or near the vWF/FVIII binding domain. Three antibodies recognize the same region within the vWF A2 repeat. Mutations near this region appear to be responsible for Type IIA von Willebrand's disease. The co-localization of these antibodies suggests that this domain might be exposed on the surface of vWF, consistent with its apparent increased sensitivity to plasma proteases.

A synthetic factor VIII peptide of eight amino acid residues (1677-1684) contains the binding region of an anti-factor VIII antibody which inhibits the binding of factor VIII to von Willebrand factor.

The monoclonal anti-factor VIII (FVIII) antibody C4 has previously been reported to inhibit the binding of purified FVIII to immobilized von Willebrand factor (vWF). The binding area of C4 was identified to be within fifteen amino acid residues (1670-1684) based on the ability of a synthetic FVIII peptide consisting of amino acid residues 1670-1684 to completely inhibit the binding of C4 to FVIII. We now report the further localization of the binding region of C4 to within eight amino acid residues (1677-1684) of FVIII light chain. Nine new overlapping FVIII peptides were synthesized based on the amino acid sequence of the acidic region of FVIII light chain and tested, along with seven previously tested peptides, for the ability to inhibit C4 binding to FVIII in an ELISA assay. Three synthetic FVIII peptides 1670-1684, 1675-1690, and 1677-1684 demonstrated dose dependent inhibition of C4 binding to FVIII. The three reactive peptides contain residues 1677-1684 in common. Since C4 can completely inhibit the binding of FVIII to vWF, this report further localizes an eight amino acid residue region of FVIII which may be important in the mediation of vWF binding.

Synthetic factor VIII peptides with amino acid sequences contained within the C2 domain of factor VIII inhibit factor VIII binding to phosphatidylserine.

The effective activation of factor X by factor IXa requires the co-factor activity of activated factor VIII (FVIII). Factor Xa formation is also dependent on the presence of negatively charged phospholipid. A phospholipid binding domain of FVIII has been reported to be present on the FVIII light chain. Recent observations on a subset of human FVIII inhibitors have implicated the carboxyl-terminal C2 domain of FVIII as containing a possible phospholipid binding site. The purpose of this study was to investigate directly the role of the C2 domain in phospholipid binding. Twenty-six overlapping peptides, which span the entire C2 domain of FVIII, were synthesized. The ability of these peptides to inhibit the binding of purified human FVIII to immobilized phosphatidylserine was evaluated in an enzyme-linked immunosorbent assay. Three overlapping synthetic FVIII peptides, 2303-2317, 2305-2332, and 2308-2322, inhibited FVIII binding to phosphatidylserine by greater than 90% when tested at a concentration of 100 mumols/L. A fourth partially overlapping peptide, 2318-2332, inhibited FVIII binding by 65%. These results suggest that the area described by these peptides, residues 2303 to 2332, may play an important role in the mediation of FVIII binding to phospholipid.

Luminographic detection of von Willebrand factor multimers in agarose gels and on nitrocellulose membranes.

Two methods for visualization of vWf multimers were compared with respect to sensitivity and detection of normal vWf and vWd variants IIA, IIB, IIC, IID, IIE, and IIF. Autoradiography and luminography after electrotransfer of vWf multimers onto nitrocellulose showed comparable sensitivity with vWf:Ag detectable after 1:500 dilution of normal plasma. The least sensitive method was luminography in agarose gels with vWf:Ag detectable after 1:300 dilution of normal plasma. No difference existed in the banding patterns of plasmas from patients with variant vWd.

Enhanced botrocetin-induced type IIB von Willebrand factor binding to platelet glycoprotein Ib initiates hyperagglutination of normal platelets.

Botrocetin, a protein isolated from the venom of the snake Bothrops jararaca, induces platelet aggregation/agglutination by von Willebrand factor (vWF) binding to the membrane glycoprotein (GP) Ib, an action resembling that of ristocetin. However, some differences in the interaction between vWF and platelet GPIb induced by these two substances have been reported. We have recently shown that the GPIb binding domain on the vWF molecule, in both instances, resides in the tryptic 52/48 kDa fragment extending from amino acid residue 449 to 728 of the constituent subunit. In the present report, we demonstrate that botrocetin does not induce agglutination of formalin-fixed platelets from a patient with Bernard-Soulier syndrome congenitally lacking GPIb and GPIX as well as GPV, a finding similar to that shown with ristocetin. A monoclonal antibody against GPIb (AP-1) inhibits either ristocetin- or botrocetin-dependent vWF binding to formalin-fixed platelets from normal individuals. Therefore, botrocetin-induced vWF binding to formalin-fixed platelets may reflect the interaction between vWF and platelet GPIb. To strengthen this concept, we have now found that heightened botrocetin-induced type IIB vWF binding to platelet GPIb causes hyperagglutination of normal platelets.

A murine monoclonal anti-factor VIII inhibitory antibody and two human factor VIII inhibitors bind to different areas within a twenty amino acid segment of the acidic region of factor VIII heavy chain.

The factor VIII (FVIII) binding regions of the monoclonal anti-FVIII inhibitory antibody C5 and a human FVIII inhibitor antibody have previously been reported to be contained within amino acid residues 351-365 of FVIII. Localization of the binding regions of these two antibodies was based on their reactivity with four synthetic FVIII peptides. Nineteen synthetic FVIII peptides spanning the entire acidic region of the FVIII heavy chain have now been evaluated for the ability to inhibit the binding of C5 to FVIII in an ELISA assay. The smallest peptide tested that inhibited C5 binding to FVIII consisted of residues 351-361. Those peptides that were able to inhibit C5 binding in the ELISA assay were also able to neutralize the FVIII inhibitory activity of C5 in plasma. The FVIII inhibitory activity of two human FVIII inhibitor antibodies was also partially neutralized by peptides from this region. Evaluation of the pattern of peptides reactive with the three antibodies indicates that the binding regions of these antibodies are in very close proximity to each other, but are not identical. Their respective binding regions are contained within residues 351-361 (C5), 354-362 (inhibitor 1), and 342-354 (inhibitor 2). These results suggest that this 20 amino acid segment of the acidic region of the heavy chain of FVIII may be functionally important in the expression of FVIII procoagulant activity.

Type II H von Willebrand disease: new structural abnormality of plasma and platelet von Willebrand factor in a patient with prolonged bleeding time and borderline levels of ristocetin cofactor activity.

In this study a new variant of type II von Willebrand disease is identified by multimeric analyses of increasing resolving power. Prior to multimeric analysis, the patient was misdiagnosed as carrying an undefined abnormality in platelet function because of his normal von Willebrand factor antigen (vWF:Ag) and low borderline ristocetin cofactor (Ricof) levels. Absence of the largest multimers from the patient's plasma and platelets was shown in a low-resolution system, but all the multimers were present in his relatives. An abnormality in the complex multimeric structure was demonstrated in both plasma and platelets with high-resolution agarose gels. The plasma of the proband and of several family members shows a broader central band with a minor, faster moving satellite band differing from the typical "triplet pattern" observed with normal plasma. Platelets show a "doublet" that runs with a mobility different from the "doublet" in normals. Therefore the proband may be either a homozygote or double heterozygote for this new abnormality. Treatment with desmopressin (DDAVP) on several occasions corrected the prolonged bleeding time of the patient only transiently. Factor VIII increased significantly, but vWF:Ag and Ricof responded poorly. We conclude that this vWF abnormality is different from those observed in the other variants (II A-G) previously described. Therefore the proposed designation for this new variant is type II H.

Isolation of the von Willebrand factor domain interacting with platelet glycoprotein Ib, heparin, and collagen and characterization of its three distinct functional sites.

We have used purified proteolytic fragments of von Willebrand factor (vWF) to characterize three related functional sites of the molecule that support interaction with platelet glycoprotein Ib, collagen, and heparin. A fragment of 116 kDa was found to be dimeric and consisted of disulfide-linked subunits which, after reduction and alkylation, corresponded to the previously described 52/48-kDa fragment extending from residue 449 to 728. Fragment III-T2, also a dimer, was composed of two pairs of disulfide-linked subunits, two 35-kDa heavy chains (residues 273-511) and two 10-kDa light chains (residues 674-728). The 116-kDa fragment, but not the constituent 52/48-kDa subunit, supported ristocetin-induced platelet aggregation and retained 20% (on a molar basis) of the ristocetin cofactor activity of native vWF; fragment III-T2 retained less than 5% activity. All three fragments, however, inhibited vWF interaction with glycoprotein Ib. Both 116-kDa and 52/48-kDa fragments inhibited vWF binding to heparin with similar potency, while fragment III-T2 had no effect in this regard. Only the 116-kDa fragment inhibited vWF binding to collagen. These results indicate that dimeric fragments containing two glycoprotein Ib-binding sites possess the minimal valency sufficient to support ristocetin-induced aggregation. The sequence comprising residues 512-673, missing in fragment III-T2, is necessary for binding to heparin and collagen and may be crucial for anchoring vWF to the subendothelium. Immunochemical and functional data suggest that the same sequence, although not essential for interaction with glycoprotein Ib, may influence the activity of the glycoprotein Ib-binding site. Only binding to collagen has absolute requirement for intact disulfide bonds. Thus, the three functional sites contained in the 116-kDa domain of vWF are structurally distinct.

Factor VIII structure and function.

The relatively recent ability to obtain highly purified factor VIII (FVIII) preparations from plasma products, the cloning of the FVIII gene, and the expression of recombinant FVIII have provided the basis for significant advancements in the understanding of the structure-function relationships of FVIII. Evaluation of the molecular structure of FVIII has revealed the presence of domains of significant internal amino acid sequence homology as well as homology with similar structural domains of factor V. Specific proteolytic cleavage sites have been identified in the molecule and the use of site directed mutagenesis has identified those proteolytic cleavage sites required for the activation of FVIII. Deletion and substitution variants of FVIII as well as the precise epitope mapping of FVIII antibodies which inhibit the procoagulant function of the protein or its binding to von Willebrand factor have provided insight into the identification of regions of FVIII which are required for normal function.