Extensive cutaneous fibrosis and ulceration caused by methadone injection.
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Drug Eruptions↗
Biomedical subjects
C Fuller
Publications and source records attributed to C Fuller.
Needle exchange programs and experience of violence in an inner city neighborhood.
OBJECTIVE: To assess the association between proximity to a needle exchange program (NEP) and experience of violence in an inner city neighborhood. METHODS: A cross-sectional survey of residents of Harlem, New York City provided data for this study. We used geocoding to obtain the distance between respondents and the nearest NEP. Respondents reported violence they were aware of or had personally experienced in their neighborhood. Multiple logistic regression analyses assessed the relation between violence and distance from the nearest NEP. RESULTS: Among 220 respondents, 50.1% were African American, 39.0% were Latino, 44.7% were male, and the mean age was 44.5 years. In separate age-, race-, sex-, and income-adjusted logistic regression models, there was no significant association between (1) reporting a fight and distance from the nearest NEP (odds ratio [OR] = 1.05, p =.89); (2) robbery in the neighborhood in the previous 6 months and distance from the nearest NEP (OR = 1.13, p =.71); (3) ever having experienced violence and distance from the nearest NEP (OR = 0.72, p =.52); or (4) ever having been robbed by drug users and distance from the nearest NEP (OR = 1.05, p =.91). CONCLUSIONS: There was no consistent association between living close to NEPs and violence reported by residents of Harlem in this study. This study suggests that NEPs do not adversely affect rates of violence in their vicinity.
Adolescent↗
Solution structure of the lipoyl domain of the chimeric dihydrolipoyl dehydrogenase P64K from Neisseria meningitidis.
The antigenic P64K protein from the pathogenic bacterium Neisseria meningitidis is found in the outer membrane of the cell, and consists of two parts: an 81-residue N-terminal region and a 482-residue C-terminal region. The amino-acid sequence of the N-terminal region is homologous with the lipoyl domains of the dihydrolipoyl acyltransferase (E2) components, and that of the C-terminal region with the dihydrolipoyl dehydrogenase (E3) components, of 2-oxo acid dehydrogenase multienzyme complexes. The two parts are separated by a long linker region, similar to the linker regions in the E2 chains of 2-oxo acid dehydrogenase complexes, and it is likely this region is conformationally flexible. A subgene encoding the P64K lipoyl domain was created and over-expressed in Escherichia coli. The product was capable of post-translational modification by the lipoate protein ligase but not aberrant modification by the biotin protein ligase of E. coli. The solution structure of the apo-domain was determined by means of heteronuclear NMR spectroscopy and found to be a flattened beta barrel composed of two four-stranded antiparallel beta sheets. The lysine residue that becomes lipoylated is in an exposed beta turn that, from a [1H]-15N heteronuclear Overhauser effect experiment, appears to enjoy substantial local motion. This structure of a lipoyl domain derived from a dihydrolipoyl dehydrogenase resembles that of lipoyl domains normally found as part of the dihydrolipoyl acyltransferase component of 2-oxo acid dehydrogenase complexes and will assist in furthering the understanding of its function in a multienzyme complex and in the membrane-bound P64K protein itself.
Amino Acid Sequence↗
Delayed onset of hemidystonia and hemiballismus following head injury: a clinicopathological correlation. Case report.
The authors report the case of a young man who suffered multiple injuries in a motor vehicle accident, the most significant of which arose in the brain, creating an unusual clinical syndrome. After experiencing an initial coma for several days, the patient was found to have a right-sided homonymous hemianopsia and a right hemiparesis, which was more marked at the shoulder and was accompanied by preservation of finger movement. Dystonic movements appeared 2 months later and progressed, along with increased spasticity on volition, to severe uncontrolled arm movements at 2 years postinjury. This motor disorder continued to worsen during the following 6 years prior to the patient's death. At autopsy, the left side of the brain was observed to have marked atrophy of the optic tract, a partial lesion of the posterior portion of the medial segment of the globus pallidus (GP), and a reduction in the size of the internal capsule at the level of the GP, suggesting impaired circulation to these areas at the time of injury. The isolated lesion of the internal segment of the GP was the presumed cause of the dystonia, acting through an alteration in thalamic inhibition. The atrophic subthalamic nucleus was the probable cause of the hemiballismus. The authors speculate that this and other delayed and progressive features of this case were the result of an active, but disordered, adaptive process that failed to compensate and, instead, caused even greater problems than the original injury.
Adult↗
Protein-protein interaction revealed by NMR T(2) relaxation experiments: the lipoyl domain and E1 component of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus.
T(2) relaxation experiments in combination with chemical shift and site-directed mutagenesis data were used to identify sites involved in weak but specific protein-protein interactions in the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. The pyruvate decarboxylase component, a heterotetramer E1(alpha(2)beta(2)), is responsible for the first committed and irreversible catalytic step. The accompanying reductive acetylation of the lipoyl group attached to the dihydrolipoyl acetyltransferase (E2) component involves weak, transient but specific interactions between E1 and the lipoyl domain of the E2 polypeptide chain. The interactions between the free lipoyl domain (9 kDa) and free E1alpha (41 kDa), E1beta (35 kDa) and intact E1alpha(2)beta(2) (152 kDa) components, all the products of genes or sub-genes over-expressed in Escherichia coli, were investigated using heteronuclear 2D NMR spectroscopy. The experiments were conducted with uniformly (15)N-labeled lipoyl domain and unlabeled E1 components. Major contact points on the lipoyl domain were identified from changes in the backbone (15)N spin-spin relaxation time in the presence and absence of E1(alpha(2)beta(2)) or its individual E1alpha or E1beta components. Although the E1alpha subunit houses the sequence motif associated with the essential cofactor, thiamin diphosphate, recognition of the lipoyl domain was distributed over sites in both E1alpha and E1beta. A single point mutation (N40A) on the lipoyl domain significantly reduces its ability to be reductively acetylated by the cognate E1. None the less, the N40A mutant domain appears to interact with E1 similarly to the wild-type domain. This suggests that the lipoyl group of the N40A lipoyl domain is not being presented to E1 in the correct orientation, owing perhaps to slight perturbations in the lipoyl domain structure, especially in the lipoyl-lysine beta-turn region, as indicated by chemical shift data. Interaction with E1 and subsequent reductive acetylation are not necessarily coupled.
Amino Acid Sequence↗
Pulmonary tumour emboli: a difficult ante-mortem diagnosis.
A woman with known metastatic breast cancer presented with subacute dyspnoea. Investigations were non-conclusive; provisional diagnoses of pulmonary thromboemboli and carcinomatous lymphangitis were made. Despite treatment the patient died 10 days after admission. Post-mortem examination showed extensive tumour emboli within the pulmonary arteries. The appropriate investigation and management of such patients is discussed.
Breast Neoplasms↗
Burkitt lymphoma is immunophenotypically different from Burkitt-like lymphoma in young persons.
INTRODUCTION: Burkitt-like lymphoma (BLL) is a provisional category of B-cell lymphoma which is morphologically intermediate between Burkitt lymphoma (BL) and large B-cell lymphoma (LBCL). The clinical significance of this morphology is controversial. PATIENTS AND METHODS: We examined 41 cases of pediatric B-cell lymphoma by immunohistochemistry for proteins associated with proto-oncogenes c-myc, BCL-2 and BCL-6 and a subset of cases (with adequate slides) for a proliferation-associated marker (Ki-67) and for apoptosis (Apop-Tag). Sixteen cases of BLL, thirteen cases of BL and twelve cases of LBCL were examined. RESULTS: Our results showed BCL-6 expression in 16 of 16 BLL, 4 of 13 BL, and 9 of 12 LBCL; c-myc expression in 14 of 15 BLL, 9 of 13 BL, and 12 of 12 LBCL; and BCL-2 expression in 2 of 16 BLL, 9 of 13 BL, and 6 of 12 LBCL. Mean apoptotic index for BLL was 10.3% (n = 6); for BL was 17.1% (n = 5); and for LBCL was 10.9% (n = 6). Ki-67 was diffusely reactive in all cases tested. There was a significantly higher proportion of BLL than BL which expressed BCL-6 (P = 0.0001). CONCLUSIONS: Labeling for BCL-6 distinguishes BLL from BL. It is likely that in children in North America, BLL is biologically distinct from BL and more closely resembles a subset of LBCL.
Adolescent↗
Testosterone urinary excretion rate increases during hypergravity in male monkeys.
Real and simulated microgravity impairs T secretion both in animals and in the human. To verify whether hypergravity might enhance T secretion as a consequence of an opposite mechanical effect, 6 male monkeys were centrifuged at 2 G for 3 weeks after a 1 G stabilization period lasting 3 weeks and then taken back to 1 G for 1 week and urine were collected daily for T excretion measurement. Significantly higher level were observed during the initial 2 G phase as compared to pre- and post centrifugation periods and the trend was the same during the remaining 2 G period. This may reflect changes in testicular perfusion rather than endocrine adaptation per se.
Animals↗
The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III).
The ALS Functional Rating Scale (ALSFRS) is a validated rating instrument for monitoring the progression of disability in patients with amyotrophic lateral sclerosis (ALS). One weakness of the ALSFRS as originally designed was that it granted disproportionate weighting to limb and bulbar, as compared to respiratory, dysfunction. We have now validated a revised version of the ALSFRS, which incorporates additional assessments of dyspnea, orthopnea, and the need for ventilatory support. The Revised ALSFRS (ALSFRS-R) retains the properties of the original scale and shows strong internal consistency and construct validity. ALSFRS-R scores correlate significantly with quality of life as measured by the Sickness Impact Profile, indicating that the quality of function is a strong determinant of quality of life in ALS.
Activities of Daily Living↗
A retrospective study of percutaneous endoscopic gastrostomy in ALS patients during the BDNF and CNTF trials.
Percutaneous endoscopic gastrostomy (PEG) provides a reliable route for nutrition and hydration in ALS patients with dysphagia. We performed a retrospective analysis of the CNTF and BDNF databases to determine the clinical status of ALS patients within 30 days preceding PEG insertion. This analysis revealed an approximately 50% reduction of function across multiple measures of ALS disease status. A trend to earlier intervention with PEG was apparent upon review of published studies and the CNTF and BDNF studies. By comparing the rate of decline pre- and post-PEG, nutritional supplementation via PEG stabilized the weight loss experienced by patients. Death within 30 days post-PEG was associated with a marked reduction in forced vital capacity (FVC) and identified a group of ALS patients in whom PEG should be cautiously performed. These data emphasize the importance of sequential measurement of FVC in managing ALS patients to guide the timing of nutritional intervention with PEG.
Adult↗
HIV prevalence and risk behaviors among new initiates into injection drug use over the age of 40 years old.
Injection drug users (IDUs) who have recently initiated an injecting career have high risk behaviors for HIV infection. The average age of an IDUs first injection is typically reported as 19-20 years, and some literature has reported 'maturing out' of drug use typically around 40 years old. The purpose of this study was to discriminate risk behaviors among newer injectors by age of initiation. This cross-sectional study includes volunteers enrolled using extensive community recruitment techniques in 1988 and 1989 in Baltimore, MD. Of the 722 injection drug users who had initiated injection within the prior six years, 124 were over 35 years old of whom 53 were 40 years and older. Rates of HIV were lower among those over 40 years (13.2%) than those who were 35-39 years (22.5%) or under 35 years old (20.9%). The behavioral characteristics of those aged 35-39 were similar to those under 35 years old, but those over 40 years old when compared with less than 39 years reported injecting at least daily less frequently (88.7% vs 76.5%, p = 0.042), using a needle from a sterile wrapper (19.0% vs 36.6%, p = 0.006), and injecting with their own works (52.6% vs 28.8%, p = 0.021). This study shows that people initiate injection drug use across a wide age range and that needle hygiene practices early after initiation tend to be safer in older compared to younger initiates.
Adult↗
Self-assembly and catalytic activity of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus.
The pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus was reconstituted in vitro from recombinant proteins derived from genes over-expressed in Escherichia coli. Titrations of the icosahedral (60-mer) dihydrolipoyl acetyltransferase (E2) core component with the pyruvate decarboxylase (E1, alpha2beta2) and dihydrolipoyl dehydrogenase (E3, alpha2) peripheral components indicated a variable composition defined predominantly by tight and mutually exclusive binding of E1 and E3 with the peripheral subunit-binding domain of each E2 chain. However, both analysis of the polypeptide chain ratios in complexes generated from various mixtures of E1 and E3, and displacement of E1 or E3 from E1-E2 or E3-E2 subcomplexes by E3 or E1, respectively, showed that the multienzyme complex does not behave as a simple competitive binding system. This implies the existence of secondary interactions between the E1 and E3 subunits and E2 that only become apparent on assembly. Exact geometrical distribution of E1 and E3 is unlikely and the results are best explained by preferential arrangements of E1 and E3 on the surface of the E2 core, superimposed on their mutually exclusive binding to the peripheral subunit-binding domain of the E2 chain. Correlation of the subunit composition with the overall catalytic activity of the enzyme complex confirmed the lack of any requirement for precise stoichiometry or strict geometric arrangement of the three catalytic sites and emphasized the crucial importance of the flexibility associated with the lipoyl domains and intramolecular acetyl group transfer in the mechanism of active-site coupling.
Binding, Competitive↗
Pigmented villonodular synovitis of the elbow: a case report and literature review.
Pigmented villonodular synovitis is a well-described, benign proliferative disorder of the synovium that rarely affects the elbow joint. Only 12 cases have been reported in this site. A case is presented of elbow involvement by pigmented villonodular synovitis that was documented by magnetic resonance imaging before surgery and monitored until recurrence.
Adult↗
Selectivity of post-translational modification in biotinylated proteins: the carboxy carrier protein of the acetyl-CoA carboxylase of Escherichia coli.
Biotin-dependent enzymes contain a biotinyl-lysine residue in a conserved sequence motif, MKM, located in a surface hairpin turn in one of the two beta-sheets that make up the domain. A sub-gene encoding the 82-residue C-terminal biotinyl domain from the biotin carboxy carrier protein of acetyl-CoA carboxylase from Escherichia coli as a fusion protein with glutathione S-transferase was created and over-expressed in E. coli. The biotinyl domain was readily released by cleavage with thrombin. Five mutant domains were created in which the conserved MKM motif was systematically replaced: by MAK and KAM, in which the target lysine is moved one place; by KKM and MKK, in which a second potential site for biotinylation is introduced; and by DKA, the motif found in the correspondingly conserved site of lipoylation in the structurally related lipoyl domains of 2-oxo acid dehydrogenase multienzyme complexes. No biotinylation of the MAK or KAM mutants was observed in vivo or by purified biotinyl protein ligase in vitro; in the KKM and MKK mutants, only one lysine residue, presumed to be that in its native position in the hairpin turn, was found to be biotinylated in vivo and in vitro. The DKA mutant was not biotinylated in vivo, but was partly lipoylated and octanoylated. It was also a poor substrate for lipoylation in vitro catalysed by the E. coli lipoyl protein ligase encoded by the lplA gene. The flanking sequence in the MKM motif is important, but not crucial, and appears to have been conserved in part to be compatible with the subsequent carboxylation reactions of biotin-dependent enzymes. The DKA motif, displayed in the hairpin loop, is sufficient to address lipoylation in E. coli but probably by a pathway different from that mediated by the lplA-dependent ligase. The recognition of the structurally homologous lipoyl and biotinyl domains by the appropriate ligase evidently has a major structural component to it, notably the positioning of the target lysine residue in the exposed hairpin loop, but there appear to be additional recognition sites elsewhere on the domains.
Acetyl-CoA Carboxylase↗
Three-dimensional structure of the major autoantigen in primary biliary cirrhosis.
BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. The major autoantigen, recognized by antibodies from > 95% of patients with PBC, has been identified as the E2 component (E2p) of the pyruvate dehydrogenase multienzyme complex. Immunodominant sites on E2p have been localized to the inner of the two lipoyl domains, where the essential cofactor lipoic acid is attached covalently. The aim of this study was to determine the three-dimensional structure of the inner lipoyl domain of human E2p. METHODS: The domain was expressed in Escherichia coli; after purification, its structure was analyzed using nuclear magnetic resonance spectroscopy. RESULTS: The structure of the lipoyl domain from human E2p was determined, and the implications of the structure for autoimmune recognition were assessed. CONCLUSIONS: Knowledge of the structure further defines the major epitope and may help in the design of antigen-specific immunotherapy for treatment of PBC.
Amino Acid Sequence↗
Psychosocial characteristics of HIV-infected adolescents in New Orleans.
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Adolescent↗
Competitive interaction of component enzymes with the peripheral subunit-binding domain of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus: kinetic analysis using surface plasmon resonance detection.
The interactions of the peripheral enzymes (E1, a pyruvate decarboxylase, and E3, dihydrolipoyl dehydrogenase) with the core component (E2, dihydrolipoyl acetyltransferase) of the pyruvate dehydrogenase (PDH) multienzyme complex of Bacillus stearothermophilus have been analyzed using a biosensor based on surface plasmon resonance detection. A recombinant di-domain (lipoyl domain plus peripheral subunit-binding domain) from E2 was attached to the biosensor chip by means of the pendant lipoyl group. The dissociation constant (Kd) for the complex between the peripheral subunit-binding domain and E3 (5.8 x 10(-10) M) was found to be almost twice that for the complex with E1 (3.24 x 10(-10) M). This was due to differences in the rate constants for dissociation (kdiss); these were 1.06 x 10(-3) and 1.87 x 10(-3) s-1 for the complexes with E1 and E3, respectively, whereas the rate constants for association (kass) were identical (3.26 x 10(6) M-1 s-1). Separate studies using non-denaturing polyacrylamide gel electrophoresis confirmed the difference in affinity and demonstrated that E1 can rapidly displace E3 from an E3-di-domain complex and vice versa. The peripheral subunit-binding domain showed no detectable interaction with the E1 alpha subunit of E1 (alpha 2 beta 2) but exhibited a strong affinity for E1 beta (Kd = 8.5 x 10(-9) M), confirming that the E1 beta subunit is responsible for binding E1 to E2. These measurements introduce new features of potential importance into the assembly and mechanism of the multienzyme complex.
Binding Sites↗
Clinical manifestations of infection with human immunodeficiency virus among adolescents in Louisiana.
PURPOSE: There is limited information regarding the clinical manifestations of human immunodeficiency virus (HIV) infection among adolescents. To better define the clinical presentation and course of HIV disease in this population, a retrospective review of all HIV-infected persons age 13-21 years at entry into a public, inner-city HIV outpatient clinic in New Orleans, Louisiana, was undertaken. RESULTS: A total of 141 adolescents were included in this study. The cohort was predominantly female (65%) and African-American (83%), and acquired HIV infection through sexual contact (89%). As many as 75% of the females and 48% of the males were diagnosed with at least one sexually transmitted disease (STD), respectively, and young African-American females with a CD4 cell count > 500/mm3 were at highest risk. The proportions of female adolescents having a gravida > or = 1 and 2 were 82% and 20%, respectively. A total of 55% of females were diagnosed with squamous intraepithelial lesions (SIL) at least once. Similar to adults, the majority of opportunistic processes occurred in adolescents with a CD4 cell count < 200/mm3. Known HIV-related symptoms (oral hairy leukoplakia, thrush, and zoster) were significantly predictive (p < .0001) for HIV disease progression. CONCLUSIONS: Although HIV-related symptoms and infections do not appear to be unique in the adolescent population, it is clear that STDs and pregnancies are common among female adolescents. Our results emphasize the need for aggressive STD and contraceptive protection counseling, and surveillance screening for STDs and cervical dysplasia.
AIDS-Related Opportunistic Infections↗