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Biomedical subjects

F W Putnam

Publications and source records attributed to F W Putnam.

At least 19 recordsLinked to original sources

Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants.

Plasma samples exhibiting alloalbuminemia on electrophoresis at pH 8.6 were requested from clinical laboratories throughout Sweden. Nine variants, each representing a different single point mutation, were found in 100 apparently unrelated Swedes. The overall prevalence of alloalbuminemia was estimated at 1:1700. Mutations were identified by protein-structural analysis followed by allele-specific DNA hybridization to verify the most common types. Slightly retarded (+1) mobility was seen in 80 cases. Of these, 71 had the Arg(-2)----Cys proalbumin variant previously called Malmö I proalbumin. Thirteen examples of the second most frequent type, the substitution Lys313----Asn and a mobility change of -1 charge unit, were found, as well as six cases of Glu570----Lys (albumin B) and a single case of Arg-1----Gln (proalbumin Christchurch). Five previously unreported types of alloalbuminemia were identified: four instances of Glu376----Gln, which is the second known mutation at this site; two examples of Asp550----Ala, the second mutation reported at this site; and one example each of Asp63----Asn, Gln268----Arg, and Asn318----Lys. Other mutations were identified among eight subjects of foreign descent. The high frequency and relatively uniform geographic distribution of the Arg-2----Cys mutation suggest that it may have occurred in a founder individual many generation ago in Sweden.

Amino Acid Sequence

Effect of incest on self and social functioning: a developmental psychopathology perspective.

The effects of child sexual abuse have become a leading concern of mental health service providers. Despite an explosion of studies, one major difficulty in this research is the lack of a developmentally sensitive model for conceptualizing short- and long-term effects and continuity and discontinuity of effects over time. This article proposes a model based in the perspective of developmental psychopathology. It is argued that incest has its unique negative effects in the domains of self and social functioning, specifically in jeopardizing self-definition and integration, self-regulatory processes, and a sense of security and trust in relationships. Studies with clinical samples indicate that diagnostic conditions associated uniquely with a history of incest reflect serious self- and social impairments. A review of the developmental literature on self and social development summarizes each major developmental transition from infancy to middle adulthood, and the implications for the negative effects of incest on development are discussed. Finally, implications for developmentally sensitive research are discussed.

Adolescent

Clinical phenomenology of child and adolescent dissociative disorders.

A comparison of two separately diagnosed samples of children and adolescents with dissociative disorders demonstrates good construct validity for these diagnoses in childhood. Descriptive analyses of the total sample reveal a clinical profile characterized by a plethora of affective, anxiety, conduct, posttraumatic, and dissociative symptoms. Children with multiple personality disorder (MPD) differ from those with dissociative disorder not otherwise specified (DDNOS) in having more amnesias, identity disturbances, and hallucinations. Adolescents were more symptomatic than children age 11 or younger and more likely to receive a diagnosis of multiple personality disorder.

Adolescent

Using hypnosis for therapeutic abreactions.

Abreaction, the dramatic reliving of traumatic events under hypnosis, is a powerful therapeutic intervention useful in the treatment of victims of trauma. First systematically applied in World War I, abreaction coupled with psychotherapeutic processing of the recovered material is increasingly being used with victims of child abuse and chronic PTSD. Abreactions are helpful in recovering dissociated or repressed traumatic material, reconnecting missing affect with recalled material and for transforming traumatic memories. Although abreactions can be induced with medications, hypnosis is the method of choice except in acute situations where it is not possible to establish rapport. A variety of hypnotic techniques for the induction and management of abreaction are discussed, together with the indications and contraindications for their use.

Abreaction

Purification and structural study of two albumin variants in an Irish population.

Two types of variant albumins were detected during routine electrophoresis on cellulose acetate on 34,000 sera from patients in a relatively stable Irish population. The fast type (IRE1) (relative mobility 1.05) had a heterozygote frequency of 1/3,780, and the slow type (IRE2) (relative mobility of 0.94) had a heterozygote frequency of 1/8,500. A method for purification of the two types of variants is described. Structural study of the fast variant established a single amino acid substitution 313 lysine----asparagine (313 Lys----Asn); this variant has been reported in several European populations and also in New Guinea indigenes. However, the slow variant has a new substitution, 479 glutamic acid----lysine (479 Glu----Lys). Because it appears to be uniquely Irish, the slow variant (formerly called IRE2) has been renamed albumin Dublin. Three other albumin variants most often reported in European populations (cumulative frequency only about 1/3,500) were not detected in this study. Because of the significance of albumin genetic variants for the study of protein evolution and as an aid in identification of drug-binding sites, clinical chemists are asked to be on the alert for cases of bisalbuminemia.

Adult

Genetic variants of serum albumin in Americans and Japanese.

A collaborative search for albumin genetic variants (alloalbumins) was undertaken by cellulose acetate and agarose electrophoresis at pH 8.6 of the sera of patients at two major medical centers in the United States and of nearly 20,000 blood donors in Japan. Seventeen instances of alloalbuminemia were ascertained, and seven different alloalbumin types were characterized by structural study. Two previously unreported alloalbumin types were identified. In one type, which was present in a Caucasian family and designated Iowa City-1, aspartic acid at position 365 was replaced by valine (365 Asp----Val); this is the second reported mutation at this position. The other type present in a Japanese blood donor had the mutation 128 His----Arg. An unexpected finding was the presence in a single Japanese of a Naskapi-type alloalbumin (372 Lys----Glu), a variant that had previously been described only for certain Amerindian tribes in whom it occurs with a polymorphic frequency (greater than 1%) and in Eti Turks. An arginyl-albumin (-1 Arg, 1 Asp----Val) occurred in an American family. The other alloalbumin types identified were proalbumins Lille and Christchurch and albumin B that have a cumulative frequency of about 1:3500 in Caucasians probably because of the hypermutability of CpG dinucleotides at the mutated sites. All of the variants characterized in this study are point mutants, and the sites are spread throughout the albumin gene. However, about one-fourth of all known albumin mutations are clustered in the sequence segment from position 354 through 382.

Amino Acid Sequence

A donor splice mutation and a single-base deletion produce two carboxyl-terminal variants of human serum albumin.

At least 35 allelic variants of human serum albumin have been sequenced at the protein level. All except two COOH-terminal variants, Catania and Venezia, are readily explainable as single-point substitutions. The two chain-termination variants are clustered in certain locations in Italy and are found in numerous unrelated individuals. In order to correlate the protein change in these variants with the corresponding DNA mutation, the two variant albumin genes have been cloned, sequenced, and compared to normal albumin genomic DNA. In the Catania variant, a single base deletion and subsequent frameshift leads to a shortened and altered COOH terminus. Albumin Venezia is caused by a mutation that alters the first consensus nucleotide of the 5' donor splice junction of intron 14 and the 3' end of exon 14, which is shortened from 68 to 43 base pairs. This change leads to an exon skipping event resulting in direct splicing of exon 13 to exon 15. The predicted Venezia albumin product has a truncated amino acid sequence (580 residues instead of 585), and the COOH-terminal sequence is altered after Glu-571. The variant COOH terminus ends with the dibasic sequence Arg-Lys that is apparently removed through stepwise cleavage by serum carboxypeptidase B to yield several forms of circulating albumin.

Amino Acid Sequence

Recent research on multiple personality disorder.

The last decade has seen the emergence of solid research on MPD and the dissociative disorders, particularly in the area of diagnosis and clinical phenomenology. A number of other areas have been opened up or advanced considerably. The most notable of these include child and adolescent dissociative disorders; investigation of dissociative memory disturbances; studies of differential alter personality psychophysiology and switching; cross-cultural comparisons of MPD, possession, and dissociative states; and the contribution of pathologic dissociation to the symptomatology of other psychiatric disorders. Yet to be attempted, however, are prospective clinical trials and treatment outcome studies. In addition to clinical and theoretical insights, recent research provides strong evidence for the validity of the diagnosis of MPD. The repeated replication of a core clinical phenomenology demonstrates a construct validity equal to or superior to that demonstrated for most DSM-III/IIIR disorders. The ability of several independently developed instruments to blindly discriminate MPD patients from nondissociative disorder patients with high rates of accuracy supports both the construct and discriminant validity of the diagnosis; and as the astute clinical observations of the last century continue to be confirmed, MPD manifests an historical validity absent in most modern era diagnoses. In the future, arguments about the "reality" of MPD cannot confine themselves merely to attacking one aspect of the disorder but rather must confront the broad range of evidence supporting the validity and reliability of the diagnosis. The future belongs to multicenter studies, although intensive single-case and personal-case series will continue to make important contributions in some areas. The essential elements necessary to begin prospective multicenter studies are rapidly coming together. Already one multicenter structured interview study of clinical phenomenology has been completed and other studies are underway or near publication. As these collaborative research networks mature, even more ambitious studies will be attempted. Adequate funding remains the principal obstacle and must be creatively addressed in this era of budgetary shortfalls, particularly as several research networks cross international boundaries. Exceptionally gratifying is the burgeoning interest of large numbers of psychiatric residents and psychology graduate students in the dissociative disorders. Thanks to a decade of hard work, the next generation of clinicians and researchers will know a great deal more about these patients than the last.

Dissociative Disorders

Dissociative disorders in children and adolescents. A developmental perspective.

Childhood and adolescent dissociative disorders are being diagnosed increasingly by mental health professionals who work with traumatized children. The identification of these conditions is hampered by the high background level of normal dissociative behavior observed in children and adolescents. An awareness of the underlying developmental processes and issues can aid in the identification of pathologic dissociation.

Adolescent

Effect of the carbohydrate moiety on the secondary structure of beta 2-glycoprotein. I. Implications for the biosynthesis and folding of glycoproteins.

By use of six highly purified exoglycosidases with well-defined specificity, the oligosaccharide units of human plasma beta 2-glycoprotein I (beta 2I) were modified by sequential enzymatic degradation. The released monosaccharides (NeuAc, Gal, GlcNAc, and Man) were quantified, and the carbohydrate compositions of the resulting glycoprotein (gp) derivatives were determined. The gp was found to be both partially sialylated and galactosylated. These findings which are in agreement with earlier reports suggest that the carbohydrate moiety of beta 2I possesses more bi- than tri-antennas, probably three of the former and two of the latter carbohydrate units. Circular dichroic (CD) spectra of native beta 2I and its derivatives were measured in aqueous buffer and 2-chloroethanol (2-CE). Analysis of these spectra for elements of secondary structure showed beta 2I and most of the derivatives to contain predominantly beta-sheet and beta-turn structures. The lack of alpha-helical structures in aqueous buffer was noted. Removal of a large portion of the carbohydrate moiety did not alter the CD spectra or secondary structure of beta 2I in either aqueous buffer or in 2-CE. However, after enzymatic removal of approximately 96% of the carbohydrate moiety, large significant changes in the spectra and secondary structures were observed. In aqueous buffer a shift in the wavelength minimum occurred, accompanied by an increase in the magnitude of the molar ellipticity and the amount of beta-turn, with a reduction in random coil. One-third of the amino acids which were originally in random coil conformation assumed beta-turns after removal of 96% of the carbohydrate moiety.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Sequence

Differential autonomic nervous system activity in multiple personality disorder.

The cardinal feature of multiple personality disorder (MPD) is the existence of two or more alter personality states that exchange control over the behaviour of an individual. Numerous clinical reports suggest that these alter personality states exhibit distinct physiological differences. We investigated differential autonomic nervous system (ANS) activity across nine subjects with MPD and five controls, who produced "alter" personality states by simulation and by hypnosis or deep relaxation. Eight of the nine MPD subjects consistently manifested physiologically distinct alter personality states. Three of the five controls were also produced physiologically distinct states, but these differed from those of the MPD subjects. A habituation paradigm demonstrated carryover effects at the ANS levels from one state to the next for both groups.

Adult

Point substitutions in albumin genetic variants from Asia.

Despite their rarity and physiologically neutral character, more inherited structural variants of serum albumin (alloalbumins) are known than for any other human protein except hemoglobin. Including three previously unreported examples described here, we have identified 13 different point substitutions in alloalbumins of Japanese origin. Of these only albumin B and two proalbumins have been reported in other ethnic groups, and these are the most common variants of European origin. Some alloalbumins of Asiatic origin, but not yet identified in Japanese, are present in diverse ethnic groups. An alloalbumin found in indigenes of New Guinea (lysine----asparagine at position 313) is also present in Caucasians of various European descents. Albumin Lambadi, occurring in a tribal group in south India, has a mutation (glutamic acid----lysine at position 501) also found as a rare variant in individuals of diverse ethnic origin resident on four continents. These results suggest that some alloalbumins with the same substitution may have originated by independent mutations in various populations. This, together with the apparent clustering of point substitutions in the protein structure, may reflect hypermutability of the albumin gene.

Amino Acid Sequence

Hypermutability of CpG dinucleotides in the propeptide-encoding sequence of the human albumin gene.

An electrophoretically slow albumin variant was detected with a phenotype frequency of about 1:1000 in Sweden and was also found in a family of Scottish descent from Kaikoura, New Zealand, and in five families in Tradate, Italy. Structural study established that the major variant component was arginyl-albumin, in which arginine at the -1 position of the propeptide is still attached to the processed albumin. A minor component with the amino-terminal sequence of proalbumin was also present as 3-6% of the total albumin. After amplification of the gene segment encoding the prepro sequence of albumin, specific hybridization of DNA to an oligonucleotide probe encoding cysteine at position -2 indicated the mutation of arginine at the -2 position to cysteine (-2 Arg----Cys). This produced the propeptide sequence Arg-Gly-Val-Phe-Cys-Arg. This was confirmed by sequence analysis after pyridylethylation of the cysteine. This mutation produces an alternate signal peptidase cleavage site in the variant proalbumin precursor of arginyl-albumin giving rise to two possible products, arginyl-albumin and the variant proalbumin. Another plasma from Bremen had an alloalbumin with a previously described substitution (1 Asp----Val), which also affects propeptide cleavage. Hypermutability of two CpG dinucleotides in the codons for the diarginyl sequence may account for the frequency of mutations in the propeptide. Mutation at these two sites results in a series of recurrent proalbumin variants that have arisen independently in diverse populations.

Amino Acid Sequence

Mutations in genetic variants of human serum albumin found in Italy.

A long-term electrophoretic survey of genetic variants of serum albumin has identified an alloalbumin in 589 unrelated individuals in Italy. The alloalbumins were classified electrophoretically into 17 types. The number of unrelated carriers for each type varied from 1 for several variants reported here to 103 for albumin B. The structural change in 8 of these types has previously been determined, and the amino acid substitutions in 3 additional types are reported here. Albumin Varese has a substitution, -2 arginine to histidine (-2 Arg----His), the same as that reported for proalbumin Lille; albumin Torino has the substitution 60 Glu----Lys; and albumin Vibo Valentia has the substitution 82 Glu----Lys. The ability to distinguish so many alloalbumin types by electrophoresis at several pH values indicates that similar substitutions at different sites produce variants with different electrophoretic mobilities. Except for chain terminations in two Italian variants, all the mutations thus far determined for alloalbumins are attributable to a single-base change in the structural gene, and there is a preponderance of transitions and purine mutations. Seven alloalbumins for which the structural change has been established have been ascertained only in Italy. Several of these are clustered in specific geographic regions of Italy, which suggests an origin through a founder individual. Other variants that occur worldwide are nonetheless clustered in geographic regions within Italy. In these cases an independent mutation probably occurred at a hypermutable site such as a CpG dinucleotide.

Amino Acid Sequence

Relation of clinical variables to dissociative phenomena in eating disorders.

In this study 30 female patients with eating disorders were compared with 30 age-matched normal female subjects. The patients demonstrated significantly higher levels of dissociative psychopathology than the comparison subjects. Furthermore, the presence of severe dissociative experience appeared to be specifically related to a propensity for self-mutilation and suicidal behavior. These findings are discussed in light of recent data which suggest that neurochemical systems shown to be abnormal in patients with eating disorders may be key pathophysiologic substrates for dissociative experience.

Adolescent