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Biomedical subjects

J Kaufman

Publications and source records attributed to J Kaufman.

At least 91 records · Page 5Linked to original sources
PubMed1997

The extracellular domain of immunodeficiency virus gp41 protein: expression in Escherichia coli, purification, and crystallization.

The env gene of SIV and HIV-1 encodes a single glycoprotein gp 160, which is processed to give a noncovalent complex of the soluble glycoprotein gp120 and the transmembrane glycoprotein gp41. The extracellular region (ectodomain), minus the N-terminal fusion peptide, of gp41 from HIV-1 (residues 27-154) and SIV (residues 27-149) have been expressed in Escherichia coli. These insoluble proteins were solubilized and subjected to a simple purification and folding scheme, which results in high yields of soluble protein. Purified proteins have a trimeric subunit composition and high alpha-helical content, consistent with the predicted coil-coil structure. SIV gp41 containing a double cysteine mutation was crystallized. The crystals are suitable for X-ray structure determination and, preliminary analysis, together with additional biochemical evidence, indicates that the gp41 trimer is arranged as a parallel bundle with threefold symmetry.

Chromatography, Gel↗
PubMed1997

Case study: trauma-related hallucinations.

Proper differential diagnosis of psychiatric disorders with psychotic symptoms is imperative, as the treatment implications of the various conditions are quite different. A case study of a 5-year-old abused child with posttraumatic stress disorder is presented to illustrate some of the characteristic features of psychotic symptoms in traumatized children. Literature reviewed suggests that trauma-related hallucinations frequently contain content which is related to children's life experiences, are exacerbated by "triggers" and safety concerns, resolve with psychotherapy or psychosocial interventions, and are resistant to standard neuroleptic treatments. They are also associated with unique clinical, familial, developmental, and psychobiological correlates, and they require multifaceted treatment interventions.

Child↗
PubMed1997

The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics.

OBJECTIVE: To develop a reliable and valid child and parent self-report instrument to screen children with anxiety disorders. METHOD: An 85-item questionnaire was administered to 341 outpatient children and adolescents and 300 parents. Utilizing item analyses and factor analyses, the original scale was reduced to 38 items. A subsample of children (n = 88) and parents (n = 86) was retested an average of 5 weeks (4 days to 15 weeks after the initial screening. RESULTS: The child and parent Screen for Child Anxiety Related Emotional Disorders (SCARED) both yielded five factors: somatic/panic, general anxiety, separation anxiety, social phobia For the total score and each of the five factors, both the child and parent SCARED demonstrated good internal consistency (alpha = .74 to .93), test-retest reliability (intraclass correlation coefficients = .70 to .90), discriminative validity (both between anxiety and other disorders and within anxiety disorders), and moderate parent-child agreement (r = .20 to .47, p < .001, all correlations). CONCLUSIONS: The SCARED shows promise as a screening instrument for anxiety disorders. Future studies using the SCARED in community samples are indicated.

Adolescent↗
PubMed1997

Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data.

OBJECTIVE: To describe the psychometric properties of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) interview, which surveys additional disorders not assessed in prior K-SADS, contains improved probes and anchor points, includes diagnosis-specific impairment ratings, generates DSM-III-R and DSM-IV diagnoses, and divides symptoms surveyed into a screening interview and five diagnostic supplements. METHOD: Subjects were 55 psychiatric outpatients and 11 normal controls (aged 7 through 17 years). Both parents and children were used as informants. Concurrent validity of the screen criteria and the K-SADS-PL diagnoses was assessed against standard self-report scales. Interrater (n = 15) and test-retest (n = 20) reliability data were also collected (mean retest interval: 18 days; range: 2 to 36 days). RESULTS: Rating scale data support the concurrent validity of screens and K-SADS-PL diagnoses. Interrater agreement in scoring screens and diagnoses was high (range: 93% to 100%). Test-retest reliability kappa coefficients were in the excellent range for present and/or lifetime diagnoses of major depression, any bipolar, generalized anxiety, conduct, and oppositional defiant disorder (.77 to 1.00) and in the good range for present diagnoses of posttraumatic stress disorder and attention-deficit hyperactivity disorder (.63 to .67). CONCLUSION: Results suggest the K-SADS-PL generates reliable and valid child psychiatric diagnoses.

Adolescent↗
PubMed1997

Serum electrolyte and blood gas changes after intrathecal and intravenous bolus injections of magnesium sulphate. An experimental study in a rat model.

The effect of intrathecally administered magnesium sulphate on serum levels of magnesium, sodium, potassium, calcium and blood gas variables was studied in a rat model. Magnesium sulphate given intrathecally has previously been shown to produce segmental spinal blockade with no permanent neurological damage. The previous studies, however, had not investigated the possible systemic effects of the magnesium sulphate. The serum magnesium level increased significantly at 1 and 2 h after the intrathecal injection of both 6.3% and 12.6% magnesium sulphate (6.3%: 28% at 1 h, 24% at 2 h; 12.6%: 22% at 1 h, 16% at 2 h). These changes were not as great as occurred when the same dose of magnesium sulphate was administered intravenously. In all cases, the serum magnesium had returned to normal by 24 h. There were no significant changes in calcium, sodium or potassium levels, nor in arterial blood gas variables. These results show that intrathecally administered magnesium sulphate has little effect on electrolyte homeostasis.

Anesthesia, Spinal↗
PubMed1997

The "minimal essential MHC" revisited: both peptide-binding and cell surface expression level of MHC molecules are polymorphisms selected by pathogens in chickens.

Birds, like mammals, have a highly polymorphic MHC that determines strong allograft rejection. However, in contrast to mammals, there are a number of viral diseases for which resistance and susceptibility are determined by particular chicken MHC haplotypes. We have found that certain common chicken MHC haplotypes express only one class I molecule at high levels. The selection on a single MHC gene should be strong, in contrast to the situation in mammals. We have determined the peptide motifs for the dominant class I molecules from a number of chicken MHC haplotypes and found that they can explain the outcome of infections with a small virus. However, the strongest MHC association is the resistance of the chicken B21 haplotype to classical Marek's disease virus, a relatively large pathogen for which any MHC molecule should find peptides. In 40 chicken lines, the level of class I expression correlates with the level of MHC-determined susceptibility to Marek's disease, the most susceptible B19 with the highest expression and the most resistant B21 with the lowest expression. Thus, cell surface expression level of class I molecules appears to be a polymorphism under selection by infectious pathogens, just like peptide-binding specificity. We speculate that these expression level differences are another manifestation of the simple MHC of chickens, which in human and mouse haplotypes are averaged out.

Animals↗
PubMed1997

Evaluation of an electronic blood pressure device for epidemiological studies.

An objective method for measuring blood pressure would enhance the usefulness of comparative survey research in hypertension. Previous studies have demonstrated that inexpensive, commercially available machines can achieve satisfactory levels of precision. We evaluated one such device in three field settings. Among 64 untreated hypertensive patients, electronic readings both in the clinic and at home were well correlated with 24 h ambulatory readings (correlation ranged from 0.6 to 0.8), consistently better than measurements obtained by human observers. Evaluation as part of a quality control exercise in an ongoing random population surveys from four countries demonstrated average correlations of 0.92 for systolic and 0.85 for diastolic between human and electronic readings. Subsequent use in survey research involving 4000 individuals in three African communities demonstrated consistency of the electronic devices. These cross-sectional surveys, in which measurements were made by non-professionals, provided qualitative estimates of rural-urban variation in blood pressure, demonstrating the practical utility of the technique. If verified by other evaluative studies, the new generation of semi-automatic electronci blood pressure devices could markedly enhance the comparability of hypertension prevalence studies.

Journal Article↗
PubMed1996

Emphysematous cystitis and pyelitis in a diabetic renal transplant recipient.

Emphysematous cystitis is a rare complication of urinary tract infection. Patients with diabetes mellitus, neurogenic bladder, bladder outlet obstruction, and recurrent urinary tract infection are at increased risk for the disease. We present a case of emphysematous cystitis and pyelitis in a diabetic renal transplant recipient. He was treated with antibiotics alone with complete clinical and radiologic resolution. The clinical course was benign, as described in most patients. The prognosis of emphysematous cystitis is good after early diagnosis and prompt treatment with appropriate antibiotics, blood glucose control, and adequate urinary drainage.

Cystitis↗
PubMed1996

The relationship between longitudinal clinical course and sleep and cortisol changes in adolescent depression.

This study examined the relationship between longitudinal clinical course and sleep and cortisol findings in adolescent unipolar major depressive disorder (MDD). Subjects were 28 adolescents (15.4 +/- 1.3 years) systematically diagnosed with unipolar MDD and 35 group-matched normal controls who participated in EEG sleep and neuroendocrine studies. Follow-up clinical assessments were conducted 7.0 +/- 0.5 years later in 94% of the original cohort. Although initial group comparisons failed to show significant differences in biologic measures, analyses incorporating clinical follow-up reveal that changes in sleep and cortisol measures are associated with differential longitudinal course. Normal controls who would develop depression after the biologic studies had shown significantly higher density of rapid eye movements (REM) and a trend for reduced REM latency compared to controls with no psychiatric disorder at follow-up. Depressed subjects with a recurrent unipolar course showed a trend towards elevated plasma cortisol near sleep onset compared to MDD subjects with no further episodes during the follow-up interval.

Adolescent↗
PubMed1996

Regulation of HIV-1 protease activity through cysteine modification.

The homodimeric protease of the human immunodeficiency virus 1 contains two cysteine residues per monomer which are highly conserved among viral isolates. However, these cysteine residues are not essential for catalytic activity which raises the question of why they are conserved. We have found previously that these cysteine residues are unusually susceptible to oxidation by metal ions, and this results in inhibition of protease activity. Recombinant protease mutants (C67A, C95A, and the double mutant C67A,C95A) were prepared to assess the possible role of these cysteines in redox regulation of the enzyme. Mixed disulfides were formed between the cysteine residues of the enzymes and low molecular weight thiols. Enzyme activity was lost when a mixed disulfide was formed between 5,5'-dithiobis(2-nitrobenzoic acid) and cysteine 95, while the same mixed disulfide at cysteine 67 reduced activity by 50%. This effect was reversible as normal activity could be restored when the enzyme was treated with dithiothreitol. The cysteines could also be modified with the common cellular thiol glutathione. Modification with glutathione was verified by mass spectrometry of the protein peaks obtained from HPLC separation. Glutathiolation of cysteine 95 abolished activity whereas modification at cysteine 67 increased the k(cat) by more than 2-fold with no effect on K(m). In addition, glutathiolation at cysteine 67 markedly stabilized the enzyme activity presumably by reducing autoproteolysis. These results demonstrate one possible mechanism for regulation of the HIV-1 protease through cysteine modification and identify additional targets for affecting protease activity other than the active site.

Catalysis↗
PubMed1996

Corticotropin-releasing hormone challenge in prepubertal major depression.

This study investigates cortisol and ACTH (corticotropin) responses to an infusion of human CRH (corticotropin-releasing hormone) in prepubertal children with major depressive disorder (MDD). Following a period of 24 hours of adaptation to the laboratory environment with an intravenous catheter in place, 34 children with MDD and 22 healthy controls received 1 microgram/kg of human CRH at 5:00 PM. Blood samples for cortisol and ACTH were measured at baseline and post-CRH. Overall, there were no significant differences between the MDD and the normal controls in baseline or post CRH stimulation values of either cortisol or ACTH. Melancholic (n = 4) patients had significantly higher baseline cortisol levels than nonmelancholic (n = 24) patients. Compared with the outpatients and the nonmelancholics, the inpatients (n = 10) and the melancholics showed significantly lower total ACTH secretion (effect size: 0.9 and 1.4, respectively) after CRH infusion. These results are consistent with a broad literature suggesting that the HPA axis abnormalities occur less frequently in early-onset depression than reported in adult studies. The pattern of results in the subgroups of inpatients and in melancholic children, however, raise questions about possible continuities with adult studies.

Adolescent↗
PubMed1996

The chicken beta 2-microglobulin gene is located on a non-major histocompatibility complex microchromosome: a small, G+C-rich gene with X and Y boxes in the promoter.

beta 2-Microglobulin is an essential subunit of major histocompatibility complex (Mhc) class I molecules, which present antigenic peptides to T lymphocytes. We sequenced a number of cDNAs and two genomic clones corresponding to chicken beta 2-microglobulin. The chicken beta 2-microglobulin gene has a similar genomic organization but smaller introns and higher G+C content than mammalian beta 2-microglobulin genes. The promoter region is particularly G+C-rich and contains, in addition to interferon regulatory elements, potential S/W, X, and Y boxes that were originally described for mammalian class II but not class I alpha or beta 2-microglobulin genes. There is a single chicken beta 2-microglobulin gene that has little polymorphism in the coding region. Restriction fragment length polymorphisms from Mhc homozygous lines, Mhc congenic lines, and backcross families, as well as in situ hybridization, show that the beta 2-microglobulin gene is located on a microchromosome different from the one that contains the chicken Mhc. We propose that the structural similarities between the beta 2-microglobulin and Mhc genes in the chicken are due to their presence on microchromosomes and suggest that these features and the microchromosomes appeared by deletion of DNA in the lineage leading to the birds.

Amino Acid Sequence↗
PubMed1996

Chicken MHC molecules, disease resistance and the evolutionary origin of birds.

Birds, like mammals, have highly a polymorphic MHC that determines strong allograft rejection. However, chickens have a much smaller, more compact and simpler MHC than mammals, as though the MHC has been stripped down to the essentials during evolution. The selection pressure on a single MHC gene should be much stronger than on a large multigene family, and, in contrast to mammals, there are a number of viral diseases for which resistance and susceptibility are determined by particular chicken MHC haplotypes. We have determined the peptide motifs for the dominant class I molecules from a number of chicken MHC haplotypes, which may explain some disease associations quite simply. Other disease associations, like the famous examples with Marek's disease, may be due to polymorphism in the level of expression of MHC class I molecules. We believe that the compact and simple nature of the MHC is due to the presence of microchromosomes in birds and suggest that the evolutionary origin of birds has been strongly influenced by the emergence of microchromosomes.

Animals↗