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PubMed2003

Relationship of personality to dissociation and childhood trauma in borderline personality disorder.

BACKGROUND: Dissociation is a prominent feature in some individuals with borderline personality disorder (BPD), yet our understanding of the meanings and implications of prominent dissociation in BPD remains limited. The purpose of this study was to investigate the relationship between dissociation and childhood trauma in BPD and to explore the relationships of dissociation and trauma to various personality features of BPD. METHODS: Twenty BPD subjects and 24 healthy comparison subjects of similar age and gender were administered the Dissociative Experiences Scale, the Childhood Trauma Questionnaire-short form, the Tridimensional Personality Questionnaire, the Defense Style Questionnaire, the Relationship Style Questionnaire, and the Schema Questionnaire. RESULTS: The BPD group exhibited greater dissociation and childhood trauma, as well as greater pathology in most personality variables, compared with the healthy group. Dissociation in BPD was not significantly related to total childhood trauma, but only to emotional neglect, which accounted for 23% of the variance in dissociation scores. CONCLUSION: Within the BPD group, dissociation was associated with fearful attachment and immature defenses, while total childhood trauma and emotional neglect were associated with overconnection and disconnection schemata. This is a preliminary study with a small sample size, yet the correlates of dissociation in BPD merit further investigation.

Adult↗
PubMed2006

Association between childhood trauma and dissociation among patients with borderline personality disorder.

OBJECTIVE: To examine the relationship between childhood trauma and dissociative experience in adulthood in patients with borderline personality disorder. METHOD: Dissociative experiences scale scores and subscale scores for the Childhood Trauma Questionnaire were correlated in 139 patients. Patients were dichotomized into high or low dissociators using the Median Dissociative Experiences Scale score as the cut-off. RESULTS: Childhood Trauma Questionnaire Subscale scores for emotional and physical abuse and emotional neglect but not sexual abuse correlated significantly with Dissociative Experiences Scale scores. High dissociators reported significantly greater levels of emotional abuse, physical abuse, emotional neglect and physical neglect but not sexual abuse than low dissociators. CONCLUSION: Patients with borderline personality disorder therefore demonstrated levels of dissociation that increased with levels of childhood trauma, supporting the hypothesis that traumatic childhood experiences engender dissociative symptoms later in life. Emotional abuse and neglect may be at least as important as physical and sexual abuse in the development of dissociative symptoms.

Adolescent↗
PubMed2002

Peritraumatic dissociation and physiological response to trauma-relevant stimuli in Vietnam combat veterans with posttraumatic stress disorder.

A recent study found that female rape victims with acute posttraumatic stress disorder (PTSD) who received a high score on the Peritraumatic Dissociative Experiences Questionnaire exhibited suppression of physiological responses during exposure to trauma-related stimuli. The goal of our present study was to test whether the same relationship holds true for male Vietnam combat veterans with chronic PTSD, using secondary analyses applied to data derived from a Veteran's Affairs Cooperative Study. Vietnam combat veterans (N = 1238) completed measures to establish combat-related PTSD diagnostic status, extent of PTSD-related symptomatic distress, and presence of dissociative symptoms during their most stressful combat-related experiences. Extreme subgroups of veterans with current PTSD were classified as either low dissociators (N = 118) or high dissociators (N = 256) based on an abbreviated version of the Peritraumatic Dissociative Experiences Questionnaire. Dependent variables reflected subjective distress along with heart rate, skin conductance, electromyographic, and blood pressure data when responding to neutral and trauma-related audiovisual and imagery presentations. Veterans in the current PTSD group had significantly higher dissociation scores than did veterans in the lifetime and never PTSD groups. Among veterans with current PTSD, high dissociators reported greater PTSD-related symptomatic distress than did low dissociators, but the groups did not differ with respect to physiological reactivity to the trauma-related laboratory presentations. Our results replicate the previously reported relationship between peritraumatic dissociation and PTSD status in Vietnam combat veterans. However, we found no association between peritraumatic dissociation and the extent of physiological responding to trauma-relevant cues in male veterans with chronic combat-related PTSD.

Adult↗
PubMed2005

Alexithymia and dissociative tendencies in an adolescent sample from Eastern Turkey.

Alexithymia and dissociative reactions are two strategies that have been put forward as coping mechanisms to alleviate painful emotions. Adult studies reveal an association between alexithymia and dissociation. In line with the coping hypothesis, it was predicted that the relationship between alexithymia and dissociative tendencies would be partly mediated by current levels of stress and past traumatic experiences. Dissociation may also be related to enhanced fantasizing, although alexithymia has traditionally been associated with an incapacity to fantasize. This relationship has not been studied well in adolescents. In the present study, 173 randomly selected high school students from Eastern Turkey were assessed with the Adolescent Dissociative Experiences Scale, the Beck Depression and Anxiety inventories, the Rosenberg Self-esteem Scale and the Toronto Alexithymia Scale. Correlation analyses followed by stepwise regression analyses were performed. "Difficulty identifying feelings" subscale of Toronto Alexithymia Scale, anxiety level and the history of physical abuse emerged as predictors of dissociative tendencies. It seems that in this group, dissociation is associated with anxiety and with difficulty in identifying feelings. Physical abuse also contributes to dissociation. The adolescent who is alexithymic may be more prone to dissociation when compared to their non-alexithymic peers. Helping alexithymic adolescents describe their body experiences may decrease their tendency to dissociation by increasing their ability to verbally identify their stressors.

Adolescent↗
PubMedDate not supplied

Dissociative symptoms in schizophrenic patients with positive and negative symptoms.

Given the close historical relationship between schizophrenia and dissociative disorders, namely multiple personality disorder, we assessed 27 ICD-10 diagnosed schizophrenic inpatients for dissociative symptoms using the German version of the Dissociative Experience Scale and compared them to a nonclinical control group matched for gender and age. Other self-report instruments covering general psychopathology, and an expert rating on the predominance of positive or negative schizophrenic symptoms, were also administered. Schizophrenic patients have significantly more dissociative symptoms than controls. Moreover, patients with a plus type of schizophrenia show significantly higher levels of dissociation than patients mainly exhibiting less productive symptoms. However, dissociative phenomena are only significantly correlated with delusions and hallucinatory behavior, and do not show any correlation with other positive symptoms of schizophrenia. Severe dissociative psychopathology is also associated with impairment in other psychopathological dimensions. The implications of these findings are discussed with regard to the theory of dissociation, the differential diagnosis between schizophrenia and dissociative disorders and a possible contribution of dissociative phenomenology to the clinical heterogeneity of schizophrenia.

Adult↗
PubMed1995

Relationship of dissociation to self-mutilation and childhood abuse in borderline personality disorder.

OBJECTIVE: This study sought to document the prevalence of dissociative experiences in adult female inpatients with borderline personality disorder and to explore the relationship between dissociation, self-mutilation, and childhood abuse history. METHOD: A treatment history interview, the Dissociative Experiences Scale, the Sexual Experiences Questionnaire, and the Hamilton Depression Rating Scale were administered to 60 consecutively admitted female inpatients with borderline personality disorder as diagnosed by the Structured Clinical Interview for DSM-III-R Personality Disorders. RESULTS: Fifty percent of the subjects had a score of 15 or more on the Dissociative Experiences Scale, indicating pathological levels of dissociation. Fifty-two percent reported a history of self-mutilation, and 60% reported a history of childhood physical and/or sexual abuse. The subjects who dissociated were more likely than those who did not to self-mutilate and to report childhood abuse. They also had higher levels of current depressive symptoms and psychiatric treatment. Multiple regression analysis demonstrated that each of these variables predicted dissociation when each of the others was controlled for, and that self-mutilation was the most powerful predictor of dissociation. CONCLUSIONS: Female inpatients with borderline personality disorder who dissociate may represent a sizable subgroup of patients with the disorder who are at especially high risk for self-mutilation, childhood abuse, depression, and utilization of psychiatric treatment. The strong correlation between dissociation and self-mutilation independent of childhood abuse history should alert clinicians to address these symptoms first while exercising caution in attributing them to a history of abuse.

Adult↗
PubMed1997

Objective assessment of peritraumatic dissociation: psychophysiological indicators.

OBJECTIVE: The aims of this study were to investigate psychophysiological changes associated with peritraumatic dissociation in female victims of recent rape and to assess the relation between these changes and symptoms of posttraumatic stress disorder (PTSD). METHOD: Eighty-five rape victims were examined in a laboratory setting within 2 weeks after the rape, and measures of heart rate, skin conductance, and nonspecific movement were collected. Self-report indexes of reactions to the trauma and interviews to assess PTSD symptoms and peritraumatic dissociation were also completed. On the basis of their scores on the Peritraumatic Dissociation Index, the subjects were classified as having low or high levels of dissociation. RESULTS: Items from the index exhibited good internal consistency, and scores were approximately normally distributed. Individuals in the high peritraumatic dissociation group showed a significantly different pattern of physiological responses from those of the low dissociation group. In general, there was a suppression of autonomic physiological responses in the high dissociation group. This group also contained a larger proportion of subjects (94%) identified as meeting PTSD symptom criteria. Also, among the high dissociation subjects there was a discrepancy between self-reports of distress and objective physiological indicators of distress in the laboratory setting. CONCLUSIONS: The results provide preliminary support for the idea that there is a dissociative subtype of persons with PTSD symptoms who exhibit diminished physiological reactivity. The results also underscore the importance of assessing dissociative symptoms in trauma survivors.

Adolescent↗
PubMed1995

Comorbidity of dissociative disorders among patients with substance use disorders.

OBJECTIVES: The study replicated methods used in an earlier study to determine the prevalence of dissociative disorders among patients with substance use disorders and to examine demographic characteristics and history of childhood abuse among patients with and without dissociative comorbidity. METHODS: A total of 100 inpatients who were completing a substance abuse treatment program at a VA medical center were interviewed using the Dissociative Disorders Interview Schedule, which diagnoses dissociative disorders. Two additional screening measures of dissociative symptoms were used, as well as an instrument to measure IQ. RESULTS: Fifteen percent of the sample were diagnosed as having a dissociative disorder. Compared with patients without a dissociative disorder, the patients with a dissociative disorder had significantly higher median scores on the two screening measures, indicating more dissociative experiences and the presence of five distinct symptom clusters. The two groups did not differ in history of childhood abuse or IQ. CONCLUSIONS: The results support earlier findings suggesting that patients with substance abuse disorder should be routinely screened for dissociative symptoms and disorders.

Adult↗
PubMed1998

Dissociative symptomatology in children and adolescents as displayed on psychological testing.

The purpose of this study was to investigate psychological testing features of children and adolescents with dissociative disorder diagnoses to provide diagnostic information that might facilitate early intervention. The psychological testing protocols of 30 children diagnosed with dissociative disorders were compared with the testing protocols of 30 consecutive admissions to the Sheppard Pratt Hospital who did not receive a dissociative identity disorder (DID; formerly termed multiple personality disorder) or dissociative disorder not otherwise specified (DDNOS) diagnosis. A rater, blind to the diagnosis, scored these protocols for the presence or absence of behavioral and testing response variables hypothesized to discriminate between the dissociative patients and the mixed group of other diagnoses. Behavioral features significantly more common in the dissociative group included forgetting, staring, unusual motor behaviors, dramatic fluctuations, fearful and angry reactions to stimuli, physical complaints during testing, and expressions of internal conflict. Significant indications of dissociation in the test responses included images of multiplicity, malevolent religiosity, dissociative coping, depersonalized imagery, emotional confusion, extreme dichotomization, images of mutilation and torture, and magical transformation. A combination of these behavioral and response variables was able to select 93% of the dissociative sample. These results add support to the discriminant validity of DID and DDNOS as diagnostic categories in childhood and provide clinical information that may be useful for early diagnosis of traumatized children with dissociative pathology.

Adolescent↗
PubMed1989

Cell dissociation techniques in human breast cancer--variations in tumor cell viability and DNA ploidy.

Approximately 70% of breast cancers contain cell populations with hyperdiploid (greater than G0/G1) DNA content; however, cells cultured from breast cancers have only diploid DNA contents and karyotypes. Mechanically dissociated cells rarely, if ever, grow in culture, while enzymatically dissociated cells do grow in most cases. To determine if cell dissociation techniques used to prepare cells for culture and other laboratory procedures select for cells with specific features, and if tumor cells are killed in the process, breast cancer cells obtained by mechanical dissociation and by enzymatic dissociation were examined for DNA content and cell viability (measured by dye exclusion). Mechanical dissociation yielded more dead cells and cells with hyperdiploid (greater than G0/G1) DNA than did enzymatic dissociation. Hyperdiploid cells were also found in the dye-excluding population with each dissociation technique, suggesting that the hyperdiploid cells were not always dead. We conclude that, in vivo, tumors contain cellular subpopulations with low viability and hyperdiploid (greater than G0/G1) DNA patterns. The extent to which these subpopulations are present in a sample depends on the dissociation technique employed. That only diploid cells are found in cultures of primary breast cancers may be because enzymatic dissociation, used to prepare cells for culture, yields predominantly diploid cells. These observations also have important implications for interpreting measurements made on dispersed cells, e.g., viability, DNA content, and other cytochemical markers.

Breast Neoplasms↗
PubMed2003

Gas-phase dissociation pathways of multiply charged peptide clusters.

Numerous studies of cluster formation and dissociation have been conducted to determine properties of matter in the transition from the condensed phase to the gas phase using materials as diverse as atomic nuclei, noble gases, metal clusters, and amino acids. Here, electrospray ionization is used to extend the study of cluster dissociation to peptides including leucine enkephalin with 7-19 monomer units and 2-5 protons, and somatostatin with 5 monomer units and 4 protons under conditions where its intramolecular disulfide bond is either oxidized or reduced. Evaporation of neutral monomers and charge separation by cluster fission are the competing dissociation pathways of both peptides. The dominant fission product for all leucine enkephalin clusters studied is a proton-bound dimer, presumably due to the high gas-phase stability of this species. The branching ratio of the fission and evaporation processes for leucine enkephalin clusters appears to be determined by the value of z2/n for the cluster where z is the charge and n the number of monomer units in the cluster. Clusters with low and high values of z2/n dissociate primarily by evaporation and cluster fission respectively, with a sharp transition between dissociation primarily by evaporation and primarily by fission measured at a z2/n value of approximately 0.5. The dependence of the dissociation pathway of a cluster on z2/n is similar to the dissociation of atomic nuclei and multiply charged metal clusters indicating that leucine enkephalin peptide clusters exist in a state that is more disordered, and possibly fluid, rather than highly structured in the dissociative transition state. The branching ratio, but not the dissociation pathway of [somatostatin5 + 4H]4+ is altered by the reduction of its internal disulfide bond indicating that monomer conformational flexibility plays a role in peptide cluster dissociation.

Disulfides↗
PubMed2005

Affective dysregulation and dissociative experience in female patients with borderline personality disorder: a startle response study.

Affective dysregulation and dissociation are currently discussed as core features of borderline personality disorder (BPD). Affective dysregulation is hypothesized to be correlated with increased amygdala functioning and dissociation is linked to inhibited processing on the amygdala and dampened autonomic output, according to the corticolimbic disconnection model of dissociation from Sierra and Berrios [Biological Psychiatry 44 (1998) 898]. We assessed startle response, which is mainly mediated by the amygdala, to investigate the relationship between affective dysregulation and dissociation. We hypothesized that patients with BPD would reveal enhanced responses to startling tones, but that these would be lessened by the presence of state dissociative experiences. 21 unmedicated female patients with BPD and 21 healthy female controls listened to 15 startling tones (95-dB, 500-ms, 1000-Hz) while heart rate, skin conductance and orbicularis oculi electromyogram responses were measured. Covariance analysis showed that the BPD group had a significantly higher startle response in the electromyogram as compared to controls. Furthermore, present-state dissociative experiences significantly influenced the startle response. Patients with low dissociative experiences revealed enhanced startle responses whereas patients with high dissociative experiences showed reduced responses. Our data support affective dysregulation in BPD as well as the corticolimbic disconnection model of dissociation, at least for EMG. Furthermore, it highlights the importance of assessing present-state dissociation in basic research as well as psychotherapy.

Adult↗
PubMed1984

The effect of exposure to charcoal and ion-exchange chromatography on the dissociation rate of estrogen from the nuclear estrogen receptor of hen oviduct.

The method of initiating dissociation of 3H-estradiol from the nuclear estrogen receptor of hen oviduct was found to have a profound effect on the dissociation rate. Likewise, prior exposure to charcoal or partial purification by ion-exchange chromatography had an effect on the dissociation rate. When the reaction was initiated by isotopic dilution with the addition of 1 microM unlabeled estradiol, dissociation of the complexes was rapid (t 1/2 approximately 3 min). When the reaction was initiated by the addition of charcoal to adsorb free steroid, the dissociation of the complexes proceeded slowly (t 1/2 approximately 30 min). Partial purification of the receptors by DEAE-Sephacel chromatography or 15 min exposure to charcoal at 0 degree C prior to initiation of the dissociation reaction by isotopic dilution produced a form of the receptor that exhibited an intermediate dissociation rate (t 1/2 approximately 10 min). The partially purified receptor that exhibited an intermediate dissociation rate was reconverted to the rapidly dissociating form in a reconstitution experiment. These data raise the possibility of a nuclear substance that regulates the rates of estrogen dissociation.

Animals↗
PubMed1991

The two calcium ions initially bound to nonphosphorylated sarcoplasmic reticulum Ca(2+)-ATPase can no longer be kinetically distinguished when they dissociate from phosphorylated ATPase toward the lumen.

Using rapid filtration, we investigated the kinetics of release toward the lumen of sarcoplasmic reticulum vesicles of the two Ca2+ ions transported by the Ca(2+)-dependent ATPase of these vesicles. Release rates at 20 degrees C were measured by three methods, with vesicles previously made leaky with an ionophore. First, we measured the rate at which 45Ca2+ bound to ATPase approached its steady-state level after addition of ATP to the 45Ca(2+)-equilibrated ATPase. At pH 6 in the absence of potassium, the observed kinetics did not reveal any very fast phase of 45Ca2+ dissociation from phosphorylated ATPase. Second, we measured the kinetics of 45Ca2+ dissociation from phosphorylated ATPase in a "chase" experiment, by isotopic dilution of calcium under turnover conditions in the presence of potassium. We found that these kinetics were essentially monophasic. Moreover, when they were measured in the presence of a high concentration of calcium, designed to saturate the low-affinity calcium transport sites on the lumenal side of the ATPase, they only departed slightly from monophasic behavior, irrespective of the experimental pH (pH 6, 7, or 9). This small perturbation by high calcium concentrations of the observed dissociation kinetics was attributed to ADP-facilitated rapid exchange of 40Ca2+ for Mg2+ at the catalytic site of phosphorylated ATPase. The third method was based on the fact that phosphorylation-induced 45Ca2+ occlusion occurred faster than 45Ca2+ dissociation from nonphosphorylated ATPase: here, we measured the rate of 45Ca2+ internalization on addition to 45Ca(2+)-saturated ATPase of an unlabeled ATP-containing medium. This method allowed separate observation of the dissociation kinetics of each of the two 45Ca2+ ions bound to phosphorylated ATPase, after either one or the other had been labeled by a preliminary partial isotopic exchange in the non-phosphorylated state of the ATPase. We found that after ATP-induced phosphorylation, the two 45Ca2+ ions dissociated toward the lumenal medium with virtually identical rate constants; this was observed under different ionic and pH conditions and also in the presence of a high Ca2+ concentration. As a control, the same partial isotopic exchange procedure allowed us to confirm that, in contrast, when ATP was absent from the final dissociation medium, the two 45Ca2+ ions dissociated from nonphosphorylated ATPase toward the cytoplasmic medium at different rates, the one bound more deeply only dissociating after a lag period corresponding to dissociation of the superficial one.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1994

Intermediate states of assembly in the dissociation of gastropod hemocyanin by hydrostatic pressure.

Under physiological conditions, the oxygen-transport protein from the gastropod Megalobulimulus ovatus, an extracellular hemocyanin, is composed of 20 identical subunits organized into a cylindrical structure (M(r) 9 x 10(6); 100 S). It dissociates in the pressure range of 0.4-2.5 kbar, as observed by spectroscopic methods (light scattering and intrinsic fluorescence) and gel filtration. In contrast to what is seen with smaller proteins, especially dimers, the pressure-dissociation curves for hemocyanin show little dependence on concentration, suggesting that native hemocyanin exists as a population of molecules with different free energies of association. The pressure-induced dissociation results from an equilibrium in which each aggregate responds to pressure independently of the others and, at any given pressure, is in one of two states, whole or dissociated, which persists for long times when compared with the duration of the experiment. The subunit-subunit affinity of dissociated hemocyanin is much lower than that of associated subunits, suggesting that a conformational drift of monomers occurs. When hemocyanin undergoes dissociation in the absence of calcium and at high pH (> 7.2), a large fraction of the dissociated products changes to a conformation that generates stable intermediate states of assembly, lacking the ability to fully reassemble into decamers and didecamers. These intermediates consist primarily of dimers (M(r) 900,000), and they bind oxygen reversibly with a higher affinity than the native hemocyanin. The binding of calcium or protons changes the conformation back to the "associable" state, which finally generates the assembled structure. The dissociation process is highly reversible at low pH (6.8-6.0) or in the presence of millimolar concentrations of calcium. At pH 5.7, dissociation is negligible at pressures up to 2.5 kbar. A decrease in pH from 7.6 to 6.6 increases the half-dissociation pressure (p 1/2) by 1.3 kbar, corresponding to a stabilization of 1.35 kcal per mole of subunit. The effects of Ca2+ and H+ may mean that, in vivo, special ionic conditions or other factors are required to be present at the assembly sites of oligomeric proteins such as hemocyanin.

Animals↗
PubMed1994

Deterministic pressure-induced dissociation of vicilin, the 7S storage globulin from pea seeds: effects of pH and cosolvents on oligomer stability.

A thermodynamic characterization of subunit association of vicilin, a storage protein from pea seeds, was performed using a combination of hydrostatic pressure and fluorescence spectroscopy. Application of pressure up to 2.4 kbar caused dissociation of vicilin subunits, as revealed by (1) size-exclusion PPLC of pressurized samples, (2) fluorescence anisotropy measurements of a dansyl-vicilin conjugate under pressure, and (3) quenching of the intrinsic fluorescence of vicilin. Pressure dissociation data were well described by a model for dissociation of a trimer. This enabled calculation of the standard molar volume change of association (delta Vo) and the equilibrium dissociation constant at atmospheric pressure (Ko); at pH 10 these were found to be delta Vo = 146 mL/mol and Ko = 2.2 x 10(-15) M2, respectively, corresponding to C1/2 (the concentration of protein at 50% dissociation at atmospheric pressure) = 18 nM and a stabilization free energy of -19.6 kcal/mol for the oligomer. Vicilin exhibited an anomalously low dependence on protein concentration for pressure dissociation. This appeared related to conformational changes in the dissociated subunits, which caused a loss of ca. 5 kcal/mol in the free energy of association and to structural/energetic heterogeneity in the population of oligomers. Pressure dissociation was markedly pH-dependent, with a stabilization free energy loss of 3.4 kcal/mol upon raising pH from 9 to 10. Circular dichroism and intrinsic fluorescence lifetime measurements at atmospheric pressure showed that the structure of vicilin was largely unaffected by pH in the range investigated. These results suggest that the effect of pH may involve deprotonation of lysine residues participating in salt bridges between vicilin subunits. Pressure dissociation of vicilin was significantly inhibited by addition of salts (NaCl, KCl, LiCl) or glycerol. Dissociation curves obtained in the presence of salts enabled calculation of the free energies of stabilization (ranging from ca. -1.2 to -2.4 kcal/mol) of the vicilin oligomers by these cosolvents. The similar effects of salts or glycerol suggest a common mechanism of stabilization of the oligomer involving exclusion of the cosolvents from the protein interface and preferential hydration of the protein.

Fabaceae↗
PubMed1986

Dissociation of the lactose repressor protein tetramer using high hydrostatic pressure.

Dissociation of lac repressor tetramer by high hydrostatic pressures was monitored with intrinsic tryptophan fluorescence. With the assumption of complete dissociation to monomer, tryptophan polarization data gave delta V a approximately 170 mL/mol and the concentration for 50% tetramer dissociation, C1/2, was 3.8 X 10(-8) M. Upon addition of inducer, the calculated delta V a increased to approximately 220 mL/mol and the C1/2 decreased to approximately 1 X 10(-8) M, a free energy difference of approximately 0.7 kcal. These results indicate a modest stabilization of the tetramer by the presence of inducer. Monitoring the average energy of tryptophan emission demonstrated that tetramer dissociation takes place over the same range of pressures as evidenced by the polarization data and IPTG dissociation can be more or less superimposed upon tetramer dissociation depending upon the ligand concentration used. Although the two transitions cannot be separated entirely, the delta V a for the region of the pressure dependence dominated by ligand dissociation was 69 mL/mol, an unexpectedly large value. For tetramer modified with methyl methanethiosulfonate, subunit dissociation was shifted to much higher pressures and IPTG dissociation did not occur. The delta V a for subunit association was calculated as approximately 160 mL/mol, and the C1/2 was 3.5 X 10(-9) M. Interactions at the subunit interface of the modified protein are apparently stronger than in the unmodified protein. The absence of inducer dissociation from the MMTS-modified tetramer by the application of high hydrostatic pressure suggests that the volume change for inducer binding to the modified protein is much smaller than that observed for the unmodified repressor.

Escherichia coli↗
PubMed1980

Characterization of the slowly dissociable human growth hormone binding component of isolated rat hepatocytes.

Human growth hormone (hGH) bound to specific sites on rat hepatocytes. The time course of hGH dissociation was comprised of more than one component. Dissociation was resolved into rapid (t1/2 = 10.5 min) and slow (t 1/2 = 6.4 h) fractions. The amount of slowly dissociable hormone increased for the first 75 min during which time cells and [125I]hGH associated. Subsequently, the amount of slowly dissociable hGH was constant. The time courses of hGH receptor binding and subsequent retention of slowly dissociable label were similar. The capacity of hepatocytes to accumulate slowly dissociable label was saturated by hGH over the same concentration range as the high-affinity binding site (KD approximately 2 nM). This suggested that a receptor-mediated process was responsible for the accumulation of slowly dissociable hGH. Rapidly dissociable label was intact [125I]hGH and fragments resulting from growth hormone degradation. Slowly dissociable hGH recovered from hepatocytes by acid extraction was intact and immunocompetent. There was a large increase in the extent of [125I]hGH degradation between 23 and 37 degrees C. Over this temperature range, the proportion of hGH not in rapid equilibrium with the medium decreased. High concentrations of hGH decreased the amount of slowly dissociable [125I]hGH retained by hepatocytes by competing for high-affinity sites. The interaction of [125I]hGH with low-affinity degradative systems was favored by the presence of hGH. The temperature and concentration dependencies of hGH retention and degradation distinguished these proceses.

Animals↗