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Biomedical subjects

F W Putnam

Publications and source records attributed to F W Putnam.

At least 37 records · Page 2Linked to original sources
PubMed1995

Hypnotizability and dissociativity in sexually abused girls.

Research on the relation between hypnotizability and clinical dissociation has led to contradictory findings. Measures of hypnotizability and dissociation are only weakly correlated in general population samples, but studies of posttraumatic stress and dissociative disorders patients have found elevated levels of clinical dissociation and hypnotizability respectively. This study assesses the relationships among hypnotizability, clinical dissociation and traumatic antecedents in 54 sexually abused girls, ages 6-15 years, and 51 matched controls. Hypnotizability was assessed on initial evaluation and again in matched subsamples at one year using the Stanford Hypnotic Clinical Scale for Children. Clinical dissociation was assessed using the Child Dissociative Checklist. Abuse variables were extracted from Child Protective Services reports. There were no significant differences in hypnotizability between abuse and control subjects. There were significant differences in clinical dissociation initially and on 1-year retest. Hypnotizability and clinical dissociation were only weakly correlated (r(105) = .118, p = NS). However, in the abuse group, highly hypnotizable subjects were significantly more dissociative. Higher levels of clinical dissociation were associated with abuse by multiple perpetrators and co-presence of physical abuse independent of the sexual abuse. A small subgroup of "double dissociative" subjects, high in both hypnotizability and dissociativity, was identified. Double dissociation was associated with multiple perpetrators and earlier onset of sexual abuse.

Adolescent↗
PubMed1994

Analbuminemia: three cases resulting from different point mutations in the albumin gene.

Analbuminemia is a very rare recessive disorder in which subjects have little or no circulating albumin, although albumin is normally the most abundant plasma protein and has many functions. Analbuminemia is caused by a variety of mutations in the albumin gene and is exhibited only by subjects homozygous for the defect. Previously the mutation had been identified at the molecular level in only two human cases; in one case it resulted from an exon-splicing defect, and in the other case it was caused by a nucleotide insertion that caused a frameshift and premature stop codon. In this investigation we identified the mutations in three unrelated subjects from different countries. In each instance a single-nucleotide mutation produced a stop codon, but the mutations occurred at three different sites: (i) in an Italian male a C-->T transition at nt 2368 in the genomic sequence of albumin, (ii) a C-->T transition at nt 4446 for an American female, and (iii) a G-->A transition at nt 7708 in a Canadian male. The size of the albumin fragment that might have been produced for the three cases varied from 31- to 213-amino acid residues, but no evidence for a circulating albumin fragment was obtained. The paradox is that analbuminemia is extremely rare (frequency < 1 x 10(6)); yet the virtual absence of albumin is tolerable despite its multiple functions.

Adult↗
PubMed1994

Genetic variants of human serum albumin in Italy: point mutants and a carboxyl-terminal variant.

Of the > 50 different genetic variants of human serum albumin (alloalbumins) that have been characterized by amino acid or DNA sequence analysis, almost half have been identified in Italy through a long-term electrophoretic survey of serum. Previously we have reported structural studies of 11 Italian alloalbumins with point mutations, 2 different carboxyl-terminal variants, and 1 case of analbuminemia in an Italian family. This article describes confirmation by DNA sequencing of mutations previously inferred from protein sequencing of 4 of the above alloalbumins; it also reports the mutations identified by protein and DNA sequence analysis of 4 other Italian alloalbumins not previously recorded: albumin Larino, His3-->Tyr; Tradate-2 (protein sequencing only), Lys225-->Gln; Caserta, Lys276-->Asn; and Bazzano, a carboxyl-terminal variant. The first 3 have point mutations that produce a single amino acid substitution, but a nucleotide deletion causes a frameshift and an altered and truncated carboxyl-terminal sequence in albumin Bazzano. In these 4 instances the expression of the alloalbumin is variable, ranging from 10% to 70% of the total albumiN, in contrast to the usual 50% each for the normal and mutant albumin. The distribution of point mutations in the albumin gene is nonrandom; most of the 47 reported point substitutions involve charged amino acid residues on the surface of the molecule that are not concerned with ligand-binding sites.

Amino Acid Sequence↗
PubMed1994

A nucleotide insertion and frameshift cause analbuminemia in an Italian family.

In analbuminemia, a very rare inherited syndrome, subjects produce little or no albumin (1/100th to 1/1000th normal), presumably because of a mutation in the albumin gene; yet, they have only moderate edema and few related symptoms owing to a compensatory increase in other plasma proteins. Because of the virtual absence of albumin the defect must be identified at the DNA level. In this study the mutation causing analbuminemia in an Italian family was investigated by analysis of DNA from a mother and her daughter. The mother was homozygous for the trait and had a serum albumin value of < 0.01 g/dl (about 1/500th normal); the daughter was heterozygous for the trait and had a nearly normal albumin value. Molecular cloning and sequence analysis of DNA from both mother and daughter showed that the mutation is caused by a nucleotide insertion in exon 8; this produces a frameshift leading to a premature stop, seven codons downstream. The methods of heteroduplex hybridization and single-strand conformation polymorphism were used to compare the DNA of the mother and daughter to the DNA of two unrelated analbuminemic individuals (one Italian and one American). This showed that all three analbuminemic individuals had different mutations; these also differed from the mutation in the only human case previously studied at the DNA level, which was a splicing defect affecting the ligation of the exon 6-exon 7 sequences. Thus, analbuminemia may result from a variety of mutations and is genetically heterogeneous.

Amino Acid Sequence↗
PubMed1994

Hypothalamic-pituitary-adrenal axis dysregulation in sexually abused girls.

Childhood sexual abuse is associated with an increased incidence of age-concurrent and adult psychopathology. Little is known, however, about the biological manifestations and sequelae of childhood sexual abuse. In this study, we characterized the hypothalamic-pituitary-adrenal axis of a self-selected sample of sexually abused and control girls recruited from a prospective longitudinal study. Plasma ACTH and total and free cortisol responses to ovine CRH (oCRH) stimulation were measured in 13 sexually abused and 13 control girls, aged 7-15 yr. Psychiatric profiles and 24-h urinary free cortisol (UFC) measures were also obtained. Sexually abused girls had a greater incidence of suicidal ideation (chi 2 = 4.51; df = 1; P < 0.05), suicide attempts (chi 2 = 4.51; df = 1; P < 0.05), and dysthymia (chi 2 = 8.85; df = 1; P < 0.01) than control girls. Sexually abused girls showed significantly lower basal (t = 2.1; df = 24; P < 0.05), and net oCRH stimulated (t = 2.2; df = 24; P < 0.05) ACTH levels and significantly reduced total ACTH responses (t = 2.5; df = 24; P < 0.05) compared with control subjects. Their total and free basal and oCRH-stimulated plasma cortisol levels and 24-h UFC measures, however, were similar to those in controls. The attenuated plasma ACTH with corresponding robust plasma cortisol responses to oCRH stimulation and normal 24-h UFC measures in sexually abused girls suggest a dysregulatory disorder of the HPA axis in these individuals. This may reflect pituitary hyporesponsiveness to oCRH. The ability of sexually abused subjects to correct for the proposed pituitary hyporesponsiveness to CRH may be related to their young age and the presence of intact glucocorticoid feedback regulatory mechanisms.

Adolescent↗
PubMed1993

Protein and DNA sequence analysis of a 'private' genetic variant: albumin Ortonovo (Glu-505-->Lys).

Albumin Ortonovo is a slow moving variant of human serum albumin which has been found only in people coming from the small villages of Ortonovo and Nicola (Liguria, Italy) and reaches polymorphic frequency (> or = 1%) in the poorly admixed population group living in that area. This is the first report of a 'private' variant detected in a Caucasian population. It probably originated as a mutation in a founder individual many generations ago. Isoelectric focusing analysis of CNBr fragments from the purified variant localized the mutation in fragment CNBr VI (residues 447-548). This fragment was isolated on a preparative scale by reversed-phase HPLC and subjected to V8 proteinase digestion. Sequence analysis of the abnormal V8 peptide revealed that the variant arises from a previously unreported substitution at position 505 where glutamic acid has been replaced by lysine. The protein data were confirmed by DNA sequence analysis which indicated a single nucleotide change of GAA-->AAA in the corresponding codon of the structural gene. Since the amino acid substitution found in albumin Ortonovo accords with its electrophoretic mobility on cellulose acetate, residue 505 is probably exposed to the solvent. The clustering of the mutations in the intersubdomain connection linking subdomains IIIA and IIIB (residues 492-511) accords with the fact that this region lies on the molecular surface and is accessible to solvent.

Amino Acid Sequence↗
PubMed1993

cDNA and protein sequence of polymorphic macaque albumins that differ in bilirubin binding.

The rhesus monkey, Macaca mulatta, exhibits a geographically restricted polymorphism of serum albumins Mac A and Mac B that is recognized by electrophoresis and is associated with a difference in bilirubin-binding parameters. To identify the basis of the polymorphism, the cDNA and protein sequences of serum albumin from M. mulatta were determined. Screening of a lambda gt11 rhesus liver cDNA library yielded a 1988-bp cDNA sequence that encodes the complete amino acid sequence of mature albumin, the entire propeptide, and part of the prepropeptide. Isoelectric focusing and amino-terminal protein sequencing of CNBr fragments of albumin from A/A and B/B homozygotes were performed, and the structural difference was localized to a CNBr fragment (MCB3) spanning residues 124-264. Sequence analysis of lysyl endopeptidase peptides of MCB3 established that Mac A albumin has a glutamine residue at position 188 while the Mac B albumin has a glutamic residue at the same position. PCR amplification, subcloning, and DNA sequence analysis of clones from A/A and B/B homozygotes confirmed the protein sequence data and the codon difference of CAA versus GAA, respectively. Comparison of macaque and human serum albumin shows a 93.5% identity at the amino acid level. In human serum albumin, Glu188 is located close to the IIA binding pocket for ligands, probably including bilirubin. Derivatives of coumarin compete more efficiently with bilirubin for binding sites on the Mac A albumin than on the Mac B albumin. In regions where coumarin-containing plants are important food resources, Mac B albumin may confer a selective advantage because bilirubin is less readily displaced from it.

Amino Acid Sequence↗
PubMed1993

Relation of dissociative phenomena to levels of cerebrospinal fluid monoamine metabolites and beta-endorphin in patients with eating disorders: a pilot study.

Dissociation is made manifest by a failure to integrate thoughts, feelings, memories, and actions into a unified sense of consciousness. Although dissociation is presumed to be a special state of consciousness manifested by state-dependent memory and physiology, the psychobiology of dissociation is poorly understood. In this study, we examined cerebrospinal fluid levels of the major monoamine metabolites and beta-endorphin in patients with eating disorders (11 with anorexia nervosa, 16 with bulimia nervosa), while they were acutely ill. Dissociative capacity was measured using the Dissociative Experiences Scale (DES). We provide evidence that neurochemical changes in dopaminergic, serotonergic, and opioid systems may be associated with the clinical expression of dissociation in patients with eating disorders during the acute phase of their illness. These preliminary results are compatible with previous studies of neurochemical disturbances in the eating disorders and suggest that future work in dissociation should specifically include examination of these neurobiologic systems.

Adolescent↗
PubMed1993

Child sexual abuse: a model of chronic trauma.

Although there is a general consensus among concerned professionals that exposure to community violence is likely to be stressful and may contribute significantly to immediate and long-term mental health problems, there is virtually no empirical research on either its acute or enduring effects. In the absence of data, investigators planning research in this area must look to other studies of the impact of chronic environmental trauma on children, including the effects of war and child maltreatment. Research on child abuse provides an important source of information on the effects of trauma on children because it draws on both prospective and retrospective studies crossing a variety of theoretical perspectives and disciplines. The existence of data on both the acute impact of abuse on children and its chronic effects and outcomes in adults informs the generation of developmentally based psychological and biological hypotheses. This paper utilizes data from research on the acute and chronic effects of sexual abuse to discuss three broad hypotheses that may be relevant to the study of the effects of community violence on children.

Child↗
PubMed1993

Validity of the Dissociative Experiences Scale in screening for multiple personality disorder: a multicenter study.

OBJECTIVE: The Dissociative Experiences Scale has proved a reliable and valid instrument to measure dissociation in many groups, but its capacity to distinguish patients with multiple personality disorder from patients with other psychiatric disorders has not yet been conclusively tested. METHOD: A discriminant analysis was performed to classify 1,051 subjects as having or not having multiple personality disorder. Another discriminant analysis was performed on a subgroup of 883 subjects more closely representing patients in a typical psychiatric facility in terms of base rates of dissociative disorders. A cutoff score of 30 was also used to classify subjects, and Bayes's theorem, which allows for the calculation of the positive predictive value and the negative predictive value of a screening test, was applied. RESULTS: According to discriminant analysis of the total study group, the scale's sensitivity was 76% and its specificity was also 76%; according to discriminant analysis of the more representative subgroup, the scale's sensitivity was 76% and its specificity was 85%. Use of the cutoff score of 30 produced similar results. Results of the application of Bayes's theorem showed that 17% of the subjects scoring 30 or higher would actually have multiple personality disorder and 99% of those scoring less than 30 would not have multiple personality disorder. CONCLUSIONS: These results indicate that the Dissociative Experiences Scale performs quite well as a screening instrument to identify subjects with multiple personality disorder. In addition, the consistency of responses to scale items across centers indicates that the symptoms reported by patients with multiple personality disorder are highly similar across diverse geographic centers. This consistency supports the reliability and validity of the diagnosis of multiple personality disorder across centers.

Adult↗
PubMed1993

Treatment of multiple personality disorder: a survey of current practices.

OBJECTIVE: Reported cases of multiple personality disorder have increased dramatically in the last decade. Few data are available on the treatment of multiple personality disorder. Current recommendations are based on the experience of individual clinicians rather than on systematic research. METHOD: A questionnaire study of 305 clinicians representing a spectrum of mental health professionals was conducted to survey the types and relative efficacy of treatment modalities currently used with cases of multiple personality disorder. RESULTS: Individual psychotherapy facilitated by hypnosis was uniformly endorsed as the primary treatment by all practitioner groups. The average patient was in twice-weekly psychotherapy facilitated by hypnosis for 3.8 years. Antidepressant and anxiolytic medications were reported to be moderately useful adjunctive treatments. CONCLUSIONS: These findings support current impressionistic treatment recommendations for multiple personality disorder regarding the primacy of psychotherapy and the moderate benefits of psychopharmacology with antidepressant and antianxiety agents.

Adult↗