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Biomedical subjects

J A Hoffman

Publications and source records attributed to J A Hoffman.

At least 19 recordsLinked to original sources

Drug dependence scale in the Millon Clinical Multiaxial inventory.

The Million Clinical Multiaxial Inventory (MCMI versions I, II, and III) includes a scale to assess drug use problems, Scale T-Drug Dependence. Detailed drug use data from a sample of 659 known drug users along with MCMI-II results were examined to determine the operating characteristics of the MCMI-II drug dependence scale. Operating characteristics, sensitivity, specificity, positive predictive power, negative predictive power, and overall diagnostic power were calculated for base rate cutoffs and for the number of prototypic items endorsed to determine the diagnostic efficiency of Scale T-Drug Dependence in identifying regular drug users. Prototypic item cutoffs provided higher levels of diagnostic and positive predictive power than did the standard base rate cutoffs.

Adult

The validity of self-reports of drug use at treatment admission and at followup: comparisons with urinalysis and hair assays.

Studies conducted in the 1970s and early 1980s concluded that people will provide valid information about their illicit drug use when research interviews are conducted under appropriate conditions. Recent studies of treated and untreated populations using improved urinalysis techniques as well as hair analysis techniques indicate that the validity of respondents' self-reports of recent drug use may be considerably less than previously reported and may differ according to a number of factors. Results are presented from a study of clients participating in the Washington, DC, Treatment Initiative study who were assessed for drug use by interview, urinalysis, and hair analysis. At intake, almost all clients who tested positive had reported their use of heroin but fewer clients had reported their cocaine use. At posttreatment followup, clients underreported both heroin and cocaine use. Findings from treatment outcome studies that fail to validate and adjust their estimates of self-reported recent drug use should be interpreted with considerable caution.

Adult

Profiles of clients in government-funded drug user treatment settings.

This report describes profiles of 535 clients who participated in a federally-funded drug user treatment research demonstration program in Washington, D.C. The majority of clients were African-Americans (92%) and single (60%). These profiles were created to determine which types of clients were enrolled in which modalities and whether there were differences between clients placed in outpatient or residential programs after stratification by primary drug problem: heroin or cocaine. Localities which are involved in developing client placement criteria and/or managed care guidelines for treatment programs may find these profiles helpful in planning to address the multiple needs of drug users.

Adult

Characterization of the peptide binding requirements for the cloned human pancreatic polypeptide-preferring receptor.

Traditionally, neuropeptide Y (NPY) receptors have been divided into Y1 and Y2 subtypes based on peptide pharmacology and synaptic localization. Other receptor subtypes have been proposed based on preferences for NPY, peptide YY (PYY), or pancreatic polypeptide (PP). Recently, we discovered a novel human member of this receptor family exhibiting high affinity for PP and PYY. In the current study, we expressed a DNA clone encoding this human PP-preferring receptor [hPP1 (or Y4)] in Chinese hamster ovary cells and performed a peptide structure-activity study. [125I]pPYY bound to homogenates of hPP1-Chinese hamster ovary cells with a Kd of 0.064 +/- 0.006 nM and a Bmax of 244 +/- 12 fmol/mg protein. Human PP inhibited binding with a Ki of 0.023 nM, whereas human PYY (Ki = 0.31 nM) and human NPY Ki = 12 nM) were significantly less potent. Rat, porcine, and bovine PP inhibited binding with similar affinities to human PP, whereas avian PP was substantially less potent (Ki = 1 nM). Deletion of the first four amino acids reduced the affinity of bovine PP to 1 nM. Carboxyl-terminal fragments of NPY and PYY also had reduced potency compared with the native peptides. In addition, deletion of Tyr36-amide produced a substantial reduction in affinity. Pro34-substituted NPY and PYY had modestly increased affinity compared with the native peptides, although Gln34-bPP had similar affinity compared with bovine PP. The carboxyl-terminally derived Y1 antagonist 1229U91 was a very potent (Ki = 0.042 nM) inhibitor of binding to hPP1. Thus, the carboxyl-terminal region of PP seems to be the most important part of the peptide for high affinity binding to hPP1. A few key residues (amino acids 2 and 3) in the amino-terminal region of PP contribute to the high affinity of the native peptide. Thus, features required for peptide recognition by the hPP1 receptor seem to be distinct from the Y1 and Y2 receptor.

Amino Acid Sequence

Relationship between drug preference and indicators of psychiatric impairment.

This study was conducted to investigate the relationship between the indicators of psychiatric disorders of individuals and their choice of either cocaine or heroin, drugs that differ markedly in their pharmacological effects. Cocaine acts as an intense stimulant, and heroin has profound sedative effects. This investigation examined the relationship between preference for heroin or cocaine and indicators of psychiatric impairment. Data from 282 subjects were grouped according to drug of choice and analyzed. Ninety-three percent of these subjects were African-American, 32% were female, and the average age was 34. Univariate and multivariate statistical analyses, such as discriminant analyses, were used to determine group differences. The results are evaluated and interpreted in relation to both the current empirical findings and to the hypotheses and theories postulated as a result of earlier clinical observations on drug of choice and psychopathology. Discriminant analysis yielded an overall correct classification rate of 75%. The discriminant function suggests that members in the cocaine drug of choice group as contrasted with members in the heroin preference group can be characterized as more socially inhibited and more self-defeating after adjusting for differences in age, duration of use of illicit substances, and marital status. Those who favored cocaine as contrasted with those who favored heroin were more likely to have never married, be younger, and have used illicit substances for a shorter period of time.

Adult

Upper eyelid blepharoplasty. A technical comparative analysis.

The purpose of this study was to compare the results of subcuticular closure with a 5-0 polypropylene suture (Prolene) with those of closure with a running 6-0 fast-absorbing catgut approximation in upper eyelid blepharoplasty. A prospective, double-blind study was designed to compare the results of these closures in patients who presented to the Otolaryngology-Head and Neck Surgery Facial Plastic Surgery Clinic, University Hospitals of Cleveland (Ohio). Thirty consecutive patients voluntarily agreed to participate in the study, and all of them had both types of closure performed on their upper eyelids. Twenty of the 30 patients who were originally enrolled in the study complied with our follow-up recommendations, completed the study, and were the basis for this report. At the time of the procedure, a random selection of closure type was made and a variety of outcome measures were recorded, including operative time, minor complications, senior author and patient aesthetic preferences, and postoperative discomfort levels. Based on the aesthetic preferences, we are of the opinion that a running 6-0 fast-absorbing catgut suture may offer some surgeons slightly better results than a subcuticular permanent suture for closure of the upper eyelid blepharoplasty incision. Comparable morbidity was seen with both techniques. No significant differences in postoperative discomfort levels were identified.

Absorption

nup1 mutants exhibit pleiotropic defects in nuclear pore complex function.

The NUP1 gene of Saccharomyces cerevisiae encodes one member of a family of nuclear pore complex proteins (nucleoporins) conserved from yeast to vertebrates. We have used mutational analysis to investigate the function of Nup1p. Deletion of either the amino- or carboxy-terminal domain confers a lethal phenotype, but partial truncations at either end affect growth to varying extents. Amino-terminal truncation causes mislocalization and degradation of the mutant protein, suggesting that this domain is required for targeting Nup1p to the nuclear pore complex. Carboxy-terminal mutants are stable but do not have wild-type function, and confer a temperature sensitive phenotype. Both import of nuclear proteins and export of poly(A) RNA are defective at the nonpermissive temperature. In addition, nup1 mutant cells become multinucleate at all temperatures, a phenotype suggestive of a defect in nuclear migration. Tubulin staining revealed that the mitotic spindle appears to be oriented randomly with respect to the bud, in spite of the presence of apparently normal cytoplasmic microtubules connecting one spindle pole body to the bud tip. EM analysis showed that the nuclear envelope forms long projections extending into the cytoplasm, which appear to have detached from the bulk of the nucleus. Our results suggest that Nup1p may be required to retain the structural integrity between the nuclear envelope and an underlying nuclear scaffold, and that this connection is required to allow reorientation of the nucleus in response to cytoskeletal forces.

Base Sequence

Comparative cocaine abuse treatment strategies: enhancing client retention and treatment exposure.

The current investigation explores the clinical utility in providing a series of enhanced clinical services to a sample of 303 cocaine-abusing clients (primarily crack smokers) relative to a standard group therapy treatment program. In addition to examining the comparative impact of six varying psychosocial treatment approaches for cocaine abuse on client retention and treatment exposure rates, an additional emphasis has been to examine the ability of fixed and dynamic client variables in predicting client outcome in this regard. No fixed (e.g., sex, income, marital status, income level, or employment status) or dynamic (e.g., recent alcohol use, antisocial personality disorder diagnoses, or motivational variables) client characteristics were useful in predicting client retention or treatment exposure rates. Program characteristics, however, or the frequency, intensity, and/or type of treatment services offered, were related to client retention and treatment exposure. Treatment exposure and retention were significantly enhanced by providing clients with more frequent and intensive group therapy, or by adding individual treatment services to a standard group therapy treatment regimen. With a population such as cocaine abusers, who typically have an extremely high treatment dropout rate, an obvious strategy is to focus efforts on engaging and retaining clients in treatment, and maximizing levels of treatment exposure. The current findings suggest that one successful approach towards enhancing psychosocial treatments for cocaine abuse is to increase the frequency, intensity, and/or types of treatment services offered.

Adult

Parental history of substance abuse as a risk factor in predicting crack smokers' substance use, illegal activities, and psychiatric status.

The purpose of this investigation was to determine if parental substance abuse places children at a higher risk regarding their own substance abuse, illegal activities, and psychological functioning. An intake assessment was conducted with 299 crack smokers currently undergoing treatment. It revealed that clients with a parental history of substance abuse were at over twice the risk for antisocial personality disorders, had been arrested significantly more times as an adult, were more likely to report illicit drug use in the past year, and had received prior treatment more often than clients without a parental history of substance abuse. Surprisingly, no relationship was observed between parental history of substance abuse and preadult behaviors including age-of-onset of drug use, childhood conduct disorders, age at first antisocial behavior, or number of arrests before age 18. Future prevention and treatment efforts with similar populations should recognize the strong influence of the family in the development of substance abuse.

Adolescent

Phases of treatment: a practical approach to methadone maintenance treatment.

There has been an on-going controversy in the United States as to whether methadone should be used in the treatment of opiate addiction as a long-term pharmacological treatment or as a short-term medical intervention to help addicts attain an opiate-free state. This article describes a practical treatment approach which resolves this dichotomy and presents a clinical framework for the variable use of methadone to effectively meet the needs of each individual patient. The therapeutic process is highly structured and is divided into several phases of treatment for opiate addiction. The article describes each of these phases and illustrates how they can be translated into clinical/medical practice. Some of the issues regarding medical maintenance, as well as methadone tapering and maintaining subsequent abstinence, are also addressed.

Combined Modality Therapy

The v-rel oncogene: insights into the mechanism of transcriptional activation, repression, and transformation.

The v-rel oncogene product from the avian reticuloendotheliosis virus strain T corresponds to a member of the Rel-related family of enhancer-binding proteins that includes both the mammalian 50- and 65-kDa subunits of the NF-kappa B transcription factor complex. However, in contrast to NF-kappa B, v-Rel has been shown to function as a dominant-negative repressor of kappa B-dependent transcription in many mature cell types. We now demonstrate that a highly conserved motif within the Rel homology domain of v-Rel containing a consensus protein kinase A phosphorylation site is required for DNA binding, transcriptional repression, and cellular transformation mediated by this oncoprotein. However, replacement of the serine phosphate acceptor within the protein kinase A site with an alanine did not alter any of these functions of v-Rel, suggesting that phosphorylation at this site is not central to the regulation of this oncogene product. Rather, the inactive mutations appear to identify a functional domain within v-Rel required for these various biological activities. It is notable that these same mutations do not impair the ability of v-Rel to heterodimerize with the 50-kDa subunit of NF-kappa B, suggesting that v-Rel-mediated transcriptional repression likely involves direct nuclear blockade of the kappa B enhancer rather than indirect alterations in the composition of preformed cytoplasmic NF-kappa B complexes. Paradoxically, when introduced into undifferentiated F9 cells, v-Rel functions as a kappa B-specific transcriptional activator rather than as a dominant-negative repressor. These stimulatory effects of v-Rel require both the conserved protein kinase A phosphorylation site and additional unique C-terminal sequences not needed for v-Rel-mediated repression in mature cells. Retinoic acid-induced differentiation of these F9 cells restores the repressor function of v-Rel. These opposing biological actions of v-Rel occurring in cells at distinct stages of differentiation may have important implications for the mechanism of v-Rel-mediated transformation occurring in avian splenocytes.

Amino Acid Sequence

A tyrosine kinase physically associates with the beta-subunit of the human IL-2 receptor.

Cell surface expression of the high affinity IL-2R regulates, in part, the proliferative response occurring in Ag- or mitogen-activated T cells. The functional high affinity IL-2R is composed of at least two distinct ligand-binding components, IL-2R alpha (Tac, p55) and IL-2R beta (p70/75). The IL-2R beta polypeptide appears to be essential for growth signal transduction, whereas the IL-2R alpha protein participates in the regulation of receptor affinity. We have prepared and characterized two mAb, DU-1 and DU-2, that specifically react with IL-2R beta. In vitro kinase assays performed with DU-2 immunoprecipitates, but not anti-IL-2R alpha or control antibody immunoprecipitates, have revealed co-precipitation of a tyrosine kinase enzymatic activity that mediates phosphorylation of IL-2R beta. Because both IL-2R alpha and IL-2R beta lack tyrosine kinase enzymatic domains, these findings strongly suggest that noncovalent association of a tyrosine kinase with the high affinity IL-2R complex. Deletion mutants of the intracellular region of IL-2R beta, lacking either a previously described "critical domain" between amino acids 267 and 322 or the carboxyl-terminal 198 residues (IL-2R beta 88), lacked the ability to co-precipitate this tyrosine kinase activity, as measured by phosphorylation of IL-2R beta in vitro. Both of these mutants also failed to transduce growth-promoting signals in response to IL-2 in vivo. Analysis of the IL-2R beta 88 mutant receptor suggested that a second protein kinase mediating phosphorylation on serine and threonine residues physically interacts with the carboxyl terminus of IL-2R beta. This kinase may be necessary but, alone, appears to be insufficient to support a full IL-2-induced proliferative response. These studies highlight the physical association of protein kinases with the cytoplasmic domain of IL-2R beta and their likely role in IL-2-induced growth signaling mediated through the multimeric high affinity IL-2R complex.

Animals

Activation of the interleukin-2 receptor alpha gene: regulatory role for DNA-protein interactions flanking the kappa B enhancer.

The human interleukin-2 receptor alpha (IL2R alpha) gene is transcriptionally activated by both phorbol esters and the HTLV-I trans-activator (Tax) protein through a mechanism that involves the interaction of inducible DNA binding proteins with a kappa B-like enhancer element (-267 to -256). Using mutated IL2R alpha promoter constructs in transient transfection and DNA binding assays, we now demonstrate that sequences located immediately upstream and downstream of the kappa B enhancer also contribute to the regulation of IL2R alpha gene expression. One upstream sequence termed UE-1 is preferentially required for phorbol ester relative to Tax-induced activation and specifically interacts with a constitutively expressed 56-kD cellular factor. In contrast, two overlapping downstream elements between nucleotides -252 and -239 appear to be required for both phorbol ester and Tax-induced activation. One of these elements, an Sp1-like sequence, binds a constitutively expressed 100-kD T-cell protein consistent in size with Sp1 isolated from HeLa cells. The second element, located between the kappa B and Sp1 sites, resembles the decanucleotide core of the serum response element (SRE) from the c-fos gene and interacts with a constitutively expressed factor. Together, these findings implicate a functional role for multiple constitutively expressed DNA binding proteins, in addition to the inducible kappa B-specific factors, in the overall regulation of IL2R alpha gene activation.

Base Sequence

Functional changes during acute rehabilitation in patients with stroke.

The purpose of this study was to analyze functional change levels and determine Spearman rank order correlation coefficients about information gleaned from physical therapy discharge notes for a group of 212 patients with stroke who received physical therapy during an acute rehabilitation stay. Functional changes were determined in the categories of wheelchair skills, transfer ability, bed (mat) mobility, and ambulation. Comparisons also were made between a subgroup of the most severely involved patients and a subgroup of the least involved patients. The correlations between these functional changes and days of physical therapy were determined. Four conclusions were deduced: 1) All patients improved functionally after a stroke, 2) the improvement was related to the amount of time spent in physical therapy, 3) the more severely involved patients exhibited a greater relationship between functional gains and days spent in physical therapy than the least involved patients, and 4) the least involved patients exhibited the most gains in function. The implications of these findings were discussed.

Activities of Daily Living

LSD flashbacks.

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Adolescent

Emergency psychiatry training: the new old problem.

Unevenness in emergency psychiatry training is still an issue as borne out by a recent literature review. An emergency setting in a general hospital is described with its attendant problem areas for psychiatric residents' function and learning. An adaptable curriculum is reported that takes into account limits of time, finances, and faculty.

Crisis Intervention