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1.
HIV Med ; 17(2): 118-23, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26200721

ABSTRACT

OBJECTIVES: The aim of the study was to describe patient characteristics and outcomes among HIV-positive adults presenting to a Zambian tertiary care hospital with new-onset seizures. METHODS: From July 2011 to June 2013, adults with seizures and a known or probable diagnosis of HIV infection were screened for a cohort study. Demographic and clinical data were obtained, including information on engagement in HIV services and in-patient mortality. Analyses were conducted to identify characteristics associated with poor engagement in care and death. RESULTS: A total of 320 of 351 screened adults were HIV-positive, with 268 of 320 experiencing new-onset seizures. Of these, 114 of 268 (42.5%) were female, and their mean age was 36.8 years. Seventy-nine of the 268 patients (29.5%) were diagnosed with HIV infection during the index illness. Among those who were aware of their HIV-positive status, 59 of 156 (37.8%) had disengaged from care. Significant functional impairment (Karnofsky score < 50) was evident in 44.0% of patients. Cerebrospinal fluid was not obtained in 108 of 268 (40.3%). In-patient mortality outcomes were available for 214 patients, and 47 of these 214 (22.0%) died during hospitalization. Patients with significant functional impairment were more likely to undergo lumbar puncture (P = 0.046). Women and the functionally impaired were more likely to die (P = 0.04 and < 0.001, respectively). CONCLUSIONS: Despite the availability of care, less than half of HIV-infected people with new-onset seizures were actively engaged in care and in-patient mortality rates were high. In the absence of clinical contraindication, lumbar puncture should be performed to diagnose treatable conditions and reduce morbidity and mortality. Continued efforts are needed to expand community-based testing and improve HIV care retention rates. Qualitative studies are needed to elucidate factors contributing to lumbar puncture usage in this population.


Subject(s)
Delivery of Health Care/statistics & numerical data , HIV Infections/physiopathology , Health Services Accessibility/statistics & numerical data , Mass Screening/statistics & numerical data , Referral and Consultation/statistics & numerical data , Seizures/virology , Spinal Puncture/statistics & numerical data , Adolescent , Adult , CD4-Positive T-Lymphocytes , Cell Count , Child , Comorbidity , Female , HIV Infections/cerebrospinal fluid , HIV Infections/complications , HIV Infections/mortality , Hospital Mortality , Humans , Male , Prospective Studies , Seizures/cerebrospinal fluid , Seizures/etiology , Seizures/mortality , Viral Load , Zambia/epidemiology
2.
Cell ; 79(3): 407-14, 1994 Nov 04.
Article in English | MEDLINE | ID: mdl-7954808

ABSTRACT

Liddle's syndrome (pseudoaldosteronism) is an autosomal dominant form of human hypertension characterized by a constellation of findings suggesting constitutive activation of the amiloride-sensitive distal renal epithelial sodium channel. We demonstrate complete linkage of the gene encoding the beta subunit of the epithelial sodium channel to Liddle's syndrome in Liddle's original kindred. Analysis of this gene reveals a premature stop codon that truncates the cytoplasmic carboxyl terminus of the encoded protein in affected subjects. Analysis of subjects with Liddle's syndrome from four additional kindreds demonstrates either premature termination or frameshift mutations in this same carboxy-terminal domain in all four. These findings demonstrate that Liddle's syndrome is caused by mutations in the beta subunit of the epithelial sodium channel and have implications for the regulation of this epithelial ion channel as well as blood pressure homeostasis.


Subject(s)
Chromosomes, Human, Pair 16 , Hyperaldosteronism/genetics , Hypertension/genetics , Mutation , Sodium Channels/genetics , Amino Acid Sequence , Base Sequence , Chromosome Mapping , Codon, Terminator/genetics , Epithelium , Female , Genetic Linkage , Genetic Markers , Humans , Male , Molecular Sequence Data , Reading Frames/genetics , Recombination, Genetic , Syndrome
3.
Biochim Biophys Acta ; 1204(2): 181-8, 1994 Feb 16.
Article in English | MEDLINE | ID: mdl-8142458

ABSTRACT

Homologies based on structural motifs characterize conserved structures and mechanisms of maintaining function. An algorithm was developed to quantitate homology among segments of two proteins based upon structural characteristics of an amphipathic alpha-helix. This helical mimicry algorithm scored homology among sequences of two proteins in terms of: (i) presence of Leu, Ile, Val, Phe, or Met in a longitudinal, hydrophobic strip-of-helix at positions n, n + 4, n + 7, n + 11, etc. in the primary sequence, (ii) identity or chemical similarity of amino acids at intervening positions and (iii) exchanges of amino acids from positions n to n - 1, n + 3, n + 4, n + 1, n - 3, n - 4 around n (on the surface of a putative helix). While such exchanges of amino acids on the surfaces of homologous helices may conserve function, they did not maintain specific interactions of those residues with apposing groups.


Subject(s)
Muramidase/genetics , Algorithms , Amino Acid Sequence , Animals , Chickens , Humans , Molecular Sequence Data , Mutation , Sequence Homology, Amino Acid
4.
J Biol Chem ; 267(11): 7406-10, 1992 Apr 15.
Article in English | MEDLINE | ID: mdl-1313798

ABSTRACT

An alpha-helix terminates when the virtual extension of its most hydrophobic, longitudinal strip containing Leu, Ile, Val, Phe, and Met lacks those residues. In each of 247 helices a template was fitted to maximize the mean hydrophobicity of positions forming a longitudinal strip-of-helix. The template was then extended into sequences beyond the ends of the helices. Leu, Ile, Val, Phe, and Met occurred in positions in the longitudinal strip-of-helix at an increased frequency (p less than 0.001), but in the first and second positions beyond either end of each true helix, they occurred at the same frequency as for their empirical distribution over all the proteins. Excesses of Asp and Glu were found in the N-terminal loop, and of Arg, His, and Lys in specific positions about the C terminus of helices. The longitudinal hydrophobic strip, the smallest amino acid in that strip, and charged amino acids in that strip, related to rotational and longitudinal orientation of alpha-helices in 15 proteins. Adjacent helices generally crossed through their longitudinal hydrophobic strips. They usually crossed through the smallest residue in the strip. Charged residues, when they occurred in the strips, were excluded from the crossing regions.


Subject(s)
Protein Conformation , Amino Acid Sequence , Amino Acids/chemistry , Cytochrome c Group/chemistry , Cytochromes c2 , Molecular Sequence Data
5.
Vaccine ; 10(1): 3-7, 1992.
Article in English | MEDLINE | ID: mdl-1371632

ABSTRACT

We seek to identify consensus sequences in digested fragments of antigenic proteins regulating selection and major histocompatibility complex (MHC)-restricted presentation to T cells of epitopes within those fragments. One such pattern, of recurrent, hydrophobic sidechains forming a longitudinal hydrophobic strip when a sequence is coiled as an alpha-helix, is found in or near most T cell-presented epitopes. Such recurrent hydrophobicity may lead to protease-protected coiling of the fragment against endosomal membranes and transfer to MHC molecules. This concept leads to better identification of T cell-presented sequences and possible to engineering of T cell-presented vaccines to affect their potency and MHC restriction.


Subject(s)
Epitopes/chemistry , T-Lymphocytes/immunology , Amino Acid Sequence , Animals , Chemical Phenomena , Chemistry, Physical , Humans , Major Histocompatibility Complex/immunology , Molecular Sequence Data , Protein Conformation
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