Phylogeny and structure of the RING3 gene.
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Amino Acid Sequence↗
Biomedical subjects
J Kaufman
Publications and source records attributed to J Kaufman.
T2 relaxation times of hypervascular and non-hypervascular liver lesions: do hypervascular lesions mimic haemangiomas on heavily T2-weighted MR images?
AIM: To correlate the T2 relaxation times of liver lesions with their vascularity at angiography and to determine whether hypervascular lesions have similar signal intensity to haemangiomas on heavily T2-weighted MR images. PATIENTS AND METHODS: Thirty-four patients with histologically proven malignant liver lesions had both angiography and T2W (SE 3000/80,160) MR imaging (1.5 T) of the liver. Angiographically, the lesions were hypervascular in 15 and non-hypervascular in 19 patients. Fifteen additional patients with proven haemangioma also had MR imaging during the same time period. The T2 relaxation time of a representative lesion was calculated for each patient and the results compared. RESULTS: The mean T2 time for hypervascular lesions was 76 +/- 21 ms compared with 79 +/- 18 ms for non-hypervascular lesions (P = 0.61). The mean T2 relaxation time for haemangiomas was significantly longer than either group: 147 +/- 46 ms (P = 0.0001). CONCLUSION: The T2 relaxation times of hypervascular and non-hypervascular liver lesions are similar and are significantly shorter than those of haemangiomas. Therefore, hypervascular lesions should not mimic haemangiomas on heavily T2-weighted images.
Carcinoma, Hepatocellular↗
The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase.
The solution structure of HIV-1 Nef has been solved by multidimensional heteronuclear NMR spectroscopy. The construct employed to circumvent problems associated with aggregation was a double-deletion mutant (delta2-39, delta159-173) in which conformationally disordered regions of the protein at the N terminus and in a long solvent-exposed flexible loop were removed, without affecting the properties or structural integrity of the remainder of the protein. Despite the absence of any sequence similarity, the overall fold of Nef is reminiscent of that of the family of winged helix-turn-helix DNA binding proteins. The binding surface of Nef for the SH3 domain of Hck tyrosine protein kinase has been mapped and reveals a non-contiguous (in terms of amino-acid sequence) interaction surface. This unique feature may suggest possible avenues for drug design aimed at inhibiting the interaction between Nef and SH3 domains.
Amino Acid Sequence↗
Antibody reactivity profiles following immunization with diverse peptides of the PERB11 (MIC) family.
PERB11 (MIC) is a gene family possessing multiple copies located within the MHC. Structurally, PERB11 is related to the MHC class I, neonatal IgG Fc receptor (FcRn) and Zn-alpha 2-glycoprotein molecules. The MHC class I family is complex in terms of its genomic arrangement, expression and function, and available evidence suggests that the PERB11 family may be similarly complex. We have adopted an approach to study the expression of such complex gene families by immunizing with multiple peptides and by screening the resulting antibodies against a large range of tissues. The amino acid sequences of PERB11.1 and PERB11.2 as well as those of other related molecules were analysed and compared. Peptides were chosen for immunization based upon (i) loop formation within the equivalent known structure of the MHC class I molecules; (ii) immunogenicity by computer analysis; and (iii) evolutionary relationships. Antibodies in serum from immunized rabbits bound to three out of six peptides used for immunization. ELISA and immunoprecipitation demonstrated binding both to the peptides and to the PERB11.2 recombinant protein. By immunofluorescent staining of various tissues of several species, the three antisera generated overlapping profiles of activity. These included reactions with kidney, small and large intestine, oesophagus, testis, ovary and human neutrophils. This is the first description of antibodies induced by the PERB11 peptides. The extreme complexity of these profiles requires further investigation, but may be explained in terms of antibodies against diverse products of the PERB11 gene family and/or related molecules.
Amino Acid Sequence↗
Improving the process of care: the cost-quality value of interdisciplinary collaboration.
A multidisciplinary group of clinicians and administrators were convened to find innovative ways to contain costs and improve the quality of care on an inpatient orthopedic unit. This group was charged with examining all phases of care and recommending changes. The team proved to be a model of effective, successful collaboration and has enabled ambitious goals to be realized on this unit. The article outlines changes related to preoperative, intraoperative, and postoperative care and discusses the dynamics of effective interdisciplinary professional collaboration.
Boston↗
Childhood and adolescent depression: a review of the past 10 years. Part I.
OBJECTIVE: To qualitatively review the literature of the past decade covering the epidemiology, clinical characteristics, natural course, biology, and other correlates of early-onset major depressive disorder (MDD) and dysthymic disorder (DD). METHOD: A computerized search for articles published during the past 10 years was made and selected studies are presented. RESULTS: Early-onset MDD and DD are frequent, recurrent, and familial disorders that tend to continue into adulthood, and they are frequently accompanied by other psychiatric disorders. These disorders are usually associated with poor psychosocial and academic outcome and increased risk for substance abuse, bipolar disorder, and suicide. In addition, DD increases the risk for MDD. There is a secular increase in the prevalence of MDD, and it appears that MDD is occurring at an earlier age in successive cohorts. Several genetic, familial, demographic, psychosocial, cognitive, and biological correlates of onset and course of early-onset depression have been identified. Few studies, however, have examined the combined effects of these correlates. CONCLUSIONS: Considerable advances have been made in our knowledge of early-onset depression. Nevertheless, further research is needed in understanding the pathogenesis of childhood mood disorders. Toward this end, studies aimed at elucidating mechanisms and interrelationships among the different domains of risk factors are needed.
Adolescent↗
Childhood and adolescent depression: a review of the past 10 years. Part II.
OBJECTIVE: To review the literature of the past decade covering the assessment, treatment, and prevention of early-onset major depressive disorder (MDD) and dysthymic disorder (DD). METHOD: A computerized search for articles published during the past decade was made, and selected studies are presented. RESULTS: Diagnostic systems and standardized interviews have been developed to reliably assess and diagnose early-onset MDD and DD. To data, few controlled psychotherapeutic trials, in particular cognitive-behavioral therapy (CBT), and one study using fluoxetine have been shown to be efficacious in the acute management of early-onset MDD. While studies of tricyclic antidepressants have shown no difference between medication and placebo, these studies are inconclusive because of the inclusion of small samples and other methodological issues. CBT may also be useful for the prevention of MDD. No studies have been published on maintenance treatment of MDD or the treatment of early-onset DD. CONCLUSIONS: It appears that both pharmacological and psychotherapeutic interventions have a role in the acute treatment of MDD. However, further research on the separate and combined efficacy of these treatments for the acute treatment, maintenance, and prevention of early-onset MDD and DD is needed. The impact of comorbidity and psychosocial consequences of early-onset depression also emphasize the importance of utilizing a multimodal approach to treatment.
Adolescent↗
Head lice resistant to pyrethroid insecticides in Britain.
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Animals↗
High-yield production of diphtheria toxin mutants by high-density culture of C7 (beta)tox+ strains grown in a non-deferrated medium.
A high-density growth approach was utilized to produce mutated diphtheria toxin from two strains of Corynebacterium diphtheria: C7 (beta)(tox-201,tox-9) and C7 (beta)(tox-107). The cross-reacting mutants (CRM) of the diphtheria toxin are CRM9 and CRM107; both of them carry the mutation in their binding site and, as a result, have 1/300 of the systemic toxicity of the wild-type diphtheria toxin. Since iron inhibits diphtheria toxin production, the traditional approach has been to grow the bacteria in a very low iron concentration. The procedure described here involved the use of a modified, non-deferrated, growth medium that provided fast and high-density growth of the bacteria, and which, when associated with simultaneous depletion of glucose and iron, enhanced the toxin production. Oxygen-enriched air was supplied to enable the bacteria to grow to a cell density giving an absorbance of 70 at 600 nm (15-20 g/l dry weight). The maximum toxin concentration in the culture supernatant was 150 mg/l. The CRM products, which remained stable following microfiltration and ultrafiltration, could be easily purified using a two-step chromatography procedure.
Corynebacterium diphtheriae↗
Oral versus repository corticosteroid therapy after hospitalization for treatment of asthma.
Tapering regimens of oral steroids may be difficult or confusing for some patients. Repository steroids have been shown to be as effective as tapering oral doses in preventing relapse after emergency treatment. This study was undertaken to determine whether repository steroids are as effective as tapering oral steroids in preventing relapse after hospitalization for treatment of asthma. Twenty-six patients with acute exacerbations of asthma requiring treatment for 24 to 72 hours with parenteral steroids were randomized into two groups. Both groups received oral prednisone, 60 mg daily, when parenteral steroids were discontinued. At discharge, one group received intramuscular placebo and oral prednisone tapered over 8 days, and the other received 80 mg intramuscular methylprednisolone sodium acetate and oral placebo. At discharge and 2-week follow-up, patients were interviewed and examined, and spirometry results were obtained. There was little difference between groups in ratings of symptoms at discharge or follow-up. Both groups had less wheezing at follow-up than at discharge, though the improvement was significant only in the repository steroid group (p < 0.05). Mean forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow rate improved at follow-up in both groups. No significant differences in outcome were found between the oral and repository steroid groups.
Acute Disease↗
Unipolar depression in adolescents: clinical outcome in adulthood.
OBJECTIVE: This study examined the longitudinal clinical course and adult sequelae of adolescent unipolar major depressive disorder (MDD) using a controlled longitudinal design. METHOD: Subjects were 28 adolescents (15.4 +/- 1.3 years) with systematically diagnosed unipolar MDD and 35 group-matched control subjects who participated in a cross-sectional electroencephalogram sleep and neuroendocrine study. Using standardized instruments, interviewers who were blind to subjects' initial diagnoses conducted follow-up clinical assessments 7.0 +/- 0.5 years later in 94% of the original cohort. RESULTS: The depressed group showed high rates of recurrence of MDD episodes during the interval period (69%). They also had elevated rates of new-onset bipolar disorder (19%). Twenty-three percent of subjects with an initial diagnosis of MDD had no additional depressive episodes after the index assessment. The rate of new onset of depression in the controls was 21%. Low socioeconomic status predicted recurrence of depressive episodes in the MDD group. MDD subjects with recurrence(s) and controls with new onset of depression during the follow-up period had significant psychosocial morbidity, as evidenced by disruption in interpersonal relationships and dissatisfaction with life and decrease in global functioning, compared with both MDD subjects with no further episodes and control subjects who had never been psychiatrically ill. These psychosocial deficits persisted remission from depressive episode(s). CONCLUSIONS: Adolescent unipolar MDD predicts continued risk for recurrences with persistence of depressive episodes and psychosocial morbidity into adulthood. A sizable minority, however, have sustained periods of remission associated with good social adjustment.
Adolescent↗
A case-control family history study of depression in adolescents.
OBJECTIVE: To examine whether depression aggregates in the families of depressed adolescents and to determine whether clinical features and/or comorbid syndromes in the depressed adolescents change the risk of psychopathology in relatives. METHOD: Lifetime prevalence rates of psychopathology in the first-degree (n = 228) and second-degree (n = 736) relatives of 76 adolescents with major depressive disorder (MDD) and the first-degree (n = 107) and second-degree (n = 323) relatives of 34 normal control adolescents were assessed by the Family History-Research Diagnostic Criteria (FH-RDC) method using the parent/guardian as the family informant. RESULTS: Compared with the first-degree relatives of normal controls, the relatives of depressed adolescents had significantly higher lifetime rates of MDD (25% versus 13%) and "any" of the FH-RDC psychiatric disorders (53% versus 36%). The second-degree relatives of adolescents with MDD had significantly higher lifetime rates of FH-RDC "other" psychiatric disorder (12% versus 7%) and "any" of the FH-RDC psychiatric disorders (22% versus 15%) but not MDD (5% versus 6%) compared with the relatives of normal controls. The first-degree relatives of depressed adolescents who were also suicidal had increased lifetime rates of suicidal behavior which significantly cosegregated with MDD. Comorbid conduct disorder in the depressed adolescent was associated with increased rates of antisocial personality disorder in the first-degree relatives and also tended to cosegregate with MDD. CONCLUSIONS: The current study provides further evidence for the familial aggregation of depression in adolescent-onset MDD. This study also suggests that the familial aggregation of nonaffective psychiatric disorders depends on the clinical features and comorbid syndromes present in the depressed adolescent proband.
Adolescent↗
Eosinophilic pleural effusion associated with valproic acid administration.
A case of eosinophilic pleural effusion with peripheral blood eosinophilia is presented. No cause of the pleural effusion was found, but on cessation of valproic acid therapy, both the pleural effusion and eosinophilia resolved. Valproic acid should be added to the list of drugs associated with pleural fluid eosinophilia.
Adult↗
A "minimal essential Mhc" and an "unrecognized Mhc": two extremes in selection for polymorphism.
The high polymorphism of classical Mhc molecules found in mammals is not simply the result of strong selection for pathogen resistance in the recent past, since there are virtually no examples of diseases caused by infectious pathogens for which resistance is determined by particular Mhc haplotypes, and in the best-studied case, a particular aspect of malaria in humans, the selection is remarkably weak. We discuss three possibilities to explain high polymorphism in mammals: accumulating, merging and boosting. The mammalian Mhc is complicated and redundant, so that every Mhc haplotype may give some level of resistance due to multiple classical Mhc genes as well as other disease resistance genes; this frustrates the attempts to demonstrate selection for disease resistance. We have looked at two vertebrate groups that may represent two extreme examples of selection for Mhc polymorphism. Birds, like mammals, have highly a polymorphic Mhc that determines strong allograft rejection. However, chickens have a much smaller, compact and simpler Mhc than mammals, as though the Mhc has been stripped down to the essentials during evolution. The selection on a single Mhc gene should be much stronger than on a large multigene family and, in fact, 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 chicken class I molecules from a number of haplotypes, which may explain some disease associations quite simply. On the other hand, salamanders have very low Mhc polymorphism and slow allograft rejection. We have isolated axolotl Mhc molecules and shown that they cosegregate with the locus that determines graft rejection in the axolotl, have only a few alleles and only weakly stimulate axolotl T lymphocytes in mixed lymphocyte culture. We believe that salamanders have classical Mhc molecules but most T cells do not recognize them, so that there is no strong selection for polymorphism.
Amino Acid Sequence↗
Synergistic effect of basic fibroblast growth factor and methylprednisolone on neurological function after experimental spinal cord injury.
The authors evaluated the effects of exogenous basic fibroblast growth factor (bFGF) in combination with intravenous methylprednisolone on neurological function and cord angiogenesis in a model of spinal cord injury. Cord injury was produced by extradural clip compression through a T-1 laminectomy. Rats were randomized to one of six groups. Group A was given sham laminectomy without cord injury or treatment. The remaining animals were divided into five groups: untreated injury (Group B); injury treated with methylprednisolone (Group C); combined methylprednisolone and 1 microgram bFGF administered locally at the site of injury (Group D); methylprednisolone and 3 micrograms bFGF (Group E); or methylprednisolone and 3 micrograms heated bFGF (Group F). Groups C through F received treatment 1 hour after cord injury. At 1, 2, 3, and 4 weeks after surgery, neurological function of hindlimbs was assessed by blinded observers using an established multiple test method (toe spread, reflexes to extension, pain, and pressure as well as inclined plane and swim test) with tests graded and results expressed as a combined behavioral score. Animals were killed to study spinal cord angiogenesis in cord samples (2-mm sections proximal and distal to the injury site) by capillary density determination. Behavioral scores over time showed a significant difference among Groups B, C, D, E, and F (p = 0.0044), with Groups E and B maintaining highest and lowest scores, respectively. There was a linear dose effect of bFGF over time (p = 0.0187). At 4 weeks, scores showed a difference among the five groups (p = 0.006), with Group E showing higher scores than any other treatment group (for example, vs. group F: p = 0.035). There was a significant difference among the groups in gray matter capillary density counts: proximal (p = 0.0192) and distal (p = 0.024), whereas white matter capillary counts were similar across treatment groups. These results show: 1) possible synergism exists between methylprednisolone and bFGF, such that combinations of these drugs significantly enhance neurological recovery, 2) bFGF exhibits a dose-response effect in function but not in capillary density, and 3) heated, inactivated bFGF is not therapeutically effective.
Analysis of Variance↗
Evolutionary conservation of MHC class I and class II molecules--different yet the same.
Despite the underlying similarities, class I molecules seem to be more heterogeneous in structure and function than class II molecules. Many features which are shared between classical class I, certain nonclassical class I and classical class II molecules (including the patterns of dilsufide bonds and particular glycosylation sites) are also conserved in vertebrate evolution; some clearly reflect structural requirements but others may be due to similarities in function. In contrast, other features (for example, the residues involved in binding the mainchain atoms of the antigenic peptide) are different in classical class I and class II molecules, but nevertheless are highly conserved in vertebrate evolution. The residues implicated in interaction with the co-receptors CD4 and CD8 are not very well conserved in vertebrate evolution, and may reflect co-evolution of the MHC molecules with their particular co-receptors.
Amino Acid Sequence↗
A follow-up of a media-based, worksite smoking cessation program.
Described an examination of data collected 2 years following the onset of a media-based, worksite smoking cessation intervention. Thirty-eight companies in Chicago were randomly assigned to one of two experimental conditions. In the initial 3-week phase, all participants in both conditions received self-help manuals and were instructed to watch a 20-day televised series designed to accompany the manual. In addition, participants in the group (G) condition received six sessions emphasizing quitting techniques and social support. In the second phase, which continued for 12 months, employees in G participated in monthly peer-led support groups and received incentives, while participants in the nongroup (NG) condition received no further treatment. Twenty-four months after pretest, 30% of employees in G were abstinent compared to only 19.5% in NG. This study is one of the few experimentally controlled worksite smoking cessation interventions to demonstrate significant program differences 2 years following the initial intervention.
Employment↗
MHC evolution: a long term investment in defense.
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Animals↗