PubMed Health⌕ Search

Biomedical subjects

M Hendricks

Publications and source records attributed to M Hendricks.

At least 19 recordsLinked to original sources

The role of nutrition and micronutrients in paediatric HIV infection.

It has been postulated that micronutrients play a role in the pathogenesis of HIV disease. Though data are sparse, there is evidence that HIV-infected adults and children have a range of micronutrient deficiencies with increasing severity in advanced disease and in the presence of malnutrition. It appears that micronutrient deficiencies contribute to immune dysfunction, infectious morbidity and disease progression. Limited interventive studies suggest that vitamin and mineral supplementation is beneficial to HIV-infected adults and children; however, current, regimens are not evidence-based and there are no randomised controlled trials in children. There are a number of African studies under way addressing these issues.

Child↗

A proposed vitamin A supplementation programme for South Africa--design, coverage and cost.

BACKGROUND: A national survey of the micronutrient status of preschool children in South Africa established that vitamin A deficiency is a significant public health problem, requiring urgent attention. A number of immediate and long-term interventions were recommended, including the introduction of a vitamin A supplementation programme and a food fortification programme. OBJECTIVES: The aim of the study was to assist in the development and implementation of a national vitamin A supplementation programme at primary health care facilities for mothers and children. This was achieved by determining the design, coverage and cost of a national primary health care facility vitamin A supplementation programme. METHODS: Based on an extensive review of the literature, the main components of a primary health care facility vitamin A supplementation programme were identified. The annual, recurrent costs of each of the programme components were estimated for the nine provinces in South Africa. Immunisation coverage rates were used as a proxy for estimating the coverage of the programme. RESULTS: The main components of the programme were identified as: promotion, training, purchase of vitamin A capsules, distribution of vitamin A capsules to primary health care facilities, distribution of capsules to the programme beneficiaries, and monitoring and evaluation. The programme would operate from primary health care facilities and would target all children between 6 and 24 months of age and newly delivered mothers. It was estimated that the programme would cover 74% of children and 95% of postpartum women nationally. The total annual, recurrent cost of the national programme was estimated at R16.4 million. The bulk of the costs would include personnel costs, comprising 68% of the total costs. Other costs included promotion (27%), vitamin A capsules (4%) and training (1%). The cost of the programme would vary significantly by province, but the provinces' average total cost per beneficiary would be similar. CONCLUSION: A primary health care facility vitamin A supplementation programme has been designed and accompanied by an estimated overall cost and coverage for implementation. The findings of the study showed that the programme would be financially feasible and would reach the majority of children under 24 months of age. It is recommended that further research be undertaken to extend the programme to the more 'hard to reach' population using other strategies such as mass immunisation campaigns.

Adolescent↗

Differences in disclosure of sexuality among African American and White gay/bisexual men: implications for HIV/AIDS prevention.

Gay and bisexual men were asked if they had disclosed their sexuality to family members, heterosexual friends, gay friends, coworkers, health care workers, and members of their church; if they had been associated with groups made up of gays, bisexuals, and lesbians; and if they had gay/bisexual friends. White men were much more likely to disclose their sexuality, to have associated with groups and to have gay/bisexual friends. As education increased, white men were more likely, and African American men less likely, to disclose sexuality and associate with groups. Having gay/bisexual friends increased with education with both groups. The difference in disclosure can be traced to the higher social stigma apparently attached to being gay in the African American community, which may be exacerbated for more educated men. As a result, African American gay men may be less likely to participate in the fight against HIV/AIDS.

Black or African American↗

latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant.

The Drosophila latheo (lat) gene was identified in a behavioral screen for olfactory memory mutants. The original hypomorphic latP1 mutant (Boynton and Tully, 1992) shows a structural defect in adult brain. Homozygous lethal lat mutants lack imaginal discs, show little cell proliferation in the CNS of third instar larvae, and die as early pupae. latP1 was cloned, and all of the above mentioned defects of hypomorphic or homozygous lethal lat mutants were rescued with a lat+ transgene. lat encodes a novel protein with homology to a subunit of the origin recognition complex (ORC). Human and Drosophila LAT both associate with ORC2 and are related to yeast ORC3, suggesting that LAT functions in DNA replication during cell proliferation.

Amino Acid Sequence↗

Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase.

In a two-hybrid screen for proteins that interact with human PCNA, we identified and cloned a human protein (hCdc18) homologous to yeast CDC6/Cdc18 and human Orc1. Unlike yeast, in which the rapid and total destruction of CDC6/Cdc18 protein in S phase is a central feature of DNA replication, the total level of the human protein is unchanged throughout the cell cycle. Epitope-tagged protein is nuclear in G1 and cytoplasmic in S-phase cells, suggesting that DNA replication may be regulated by either the translocation of this protein between the nucleus and the cytoplasm or the selective degradation of the protein in the nucleus. Mutation of the only nuclear localization signal of this protein does not alter its nuclear localization, implying that the protein is translocated to the nucleus through its association with other nuclear proteins. Rapid elimination of the nuclear pool of this protein after the onset of DNA replication and its association with human Orc1 protein and cyclin-cdks supports its identification as human CDC6/Cdc18 protein.

Amino Acid Sequence↗

Identification of HsORC4, a member of the human origin of replication recognition complex.

A new member of human origin recognition complex (ORC) has been cloned and identified as the human homologue of Saccharomyces cerevisiae ORC4. HsORC4 is a 45-kDa protein encoded by a 2.2-kilobase mRNA whose amino acid sequence is 29% identical to ScORC4. HsORC4 has a putative nucleotide triphosphate binding motif that is not seen in ScORC4. HsORC4P also reveals an unsuspected homology to the ORC1-Cdc18 family of proteins. HsORC4 mRNA expression and protein levels remain constant through the cell cycle. HsORC4P is coimmunoprecipitated from cell extracts with another subunit of human ORC, HsORC2P, consistent with it being a part of the putative human origin recognition complex.

Amino Acid Sequence↗

Effect of combination therapy with zidovudine and didanosine on neuropsychological functioning in patients with symptomatic HIV disease: a comparison of simultaneous and alternating regimens.

OBJECTIVE: To evaluate the effects of treatment with alternating and simultaneous regimens of zidovudine and didanosine on neuropsychological function in patients with symptomatic HIV-1 disease, focusing on patients with possible HIV-1-associated central nervous system (CNS) compromise at entry. DESIGN: Randomized non-blinded clinical trial. SETTING: Government medical research center. PATIENTS: Thirty-eight patients with symptomatic HIV-1 disease, of whom 21 had evidence of CNS compromise at entry. RESULTS: After 12 weeks of therapy, overall significant improvements in memory (P < 0.01) and focused attention (P < 0.001) were seen on both regimens. These gains, however, were largely limited to those patients with HIV-1-associated CNS compromise at entry (P < 0.05). Improvements were also noted in receptive vocabulary, reading, perceptual discrimination and reasoning, divided attention, motor strength, and in mood and affect. Improvements in those latter functions were generally of limited magnitude and were of comparable size for both compromised and non-compromised patients. There was no overall difference between the two drug regimens in the effects on CNS parameters. CONCLUSIONS: Therapy-related improvements were noted particularly for patients with HIV-1-associated CNS compromise. Neuropsychological functions that have been implicated in AIDS dementia--memory and attention--showed the greatest gains. In contrast to the previously described superiority of the simultaneous regimen with regard to immunologic and virologic parameters, there was no difference between the regimens with regard to CNS measures. This supports the contention that the CNS constitutes a relative independent compartment in terms of HIV disease and treatment.

AIDS Dementia Complex↗

Inducible expression of a heterologous protein in Hansenula polymorpha using the alcohol oxidase 1 promoter of Pichia pastoris.

Pichia pastoris (Pp) and Hansenula polymorpha (Hp) are methylotrophic yeasts commonly used for industrial purposes. Growth of either of these yeasts in the presence of methanol as the carbon source results in high-level induction of alcohol oxidase expression. The respective alcohol oxidase genes, AOX1 in Pp and MOX in Hp, have similar regulatory characteristics. Our studies show that the Pp AOX1 promoter (AOX1p) can be used for methanol-induced expression of a heterologous gene in Hp. Furthermore, the size of an AOX1p-heterologous gene-AOX1 terminator cassette transcript synthesized in Hp is indistinguishable from that synthesized in Pp suggesting that transcription both initiates and terminates at the same sites in both yeast species. Induction of AOX1p in Hp demonstrates that the methanol-inducible regulatory mechanism in Hp is able to recognize and activate the Pp promoter in spite of extensive sequence variations between AOX1p and MOXp.

Alcohol Oxidoreductases↗

A novel approach to the determination and characterization of HIV dementia.

BACKGROUND: Neuropsychological studies of the pattern and extent of cognitive impairment in HIV-infected patients have mostly used deviations from control values and/or cut-off scores as criteria for classification of dementia. There is, however, no agreement as to how to define impairment, and classification is imprecise. METHOD: The current study used a dementia classification matrix, developed with a step-wise linear discriminant analysis of neuropsychological data from patients with primary neurodegenerative dementias, to classify symptomatic HIV patients as demented or non-demented, and further to differentiate cortical and subcortical dementia patterns. Thirty-two male and 2 female patients (mean age 39 +/- 2) with symptomatic HIV disease (mean absolute CD4 count 195 +/- 41) participated in the study. RESULTS: Thirty-five per cent of patients were classified as demented. Of these, 83% showed a subcortical pattern and 17% a cortical profile of deficits. Significant differences between patients classified as subcortically demented and those categorized as normal on neuropsychological measures associated with subcortical integrity further validated the classification. Measures of psychiatric status between subgroups were similar. CONCLUSION: Since certain treatments may delay or reverse cognitive deficits, the use of an objective classification method based on discriminant analysis may help to identify patients who may benefit from therapy.

AIDS Dementia Complex↗

Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system.

Glial growth factors, proteins that are mitogenic for Schwann cells, and several ligands for the p185erbB2 receptor, are products of the same gene. Alternative splicing of the messenger RNA generates an array of putative membrane-attached, intracellular and secreted signalling proteins, at least some of which are expressed in the developing spinal cord and brain. These factors are probably important in the development and regeneration of the nervous system.

Alternative Splicing↗

Assessment of the Abbott IMx assay system for the measurement of human chorionic gonadotropin levels in the treatment of ectopic pregnancy.

The rapid, accurate determination of serum human chorionic gonadotropin (beta-hCG) levels in the 900- to 2000-IU/L range is a critical element in the treatment of patients with suspected ectopic pregnancy. Using the Abbott IMx system (Abbott Laboratories, North Chicago, Ill), beta-hCG levels can be determined on an undiluted sample up to 1000 IU/L. A sample with beta-hCG level greater than 1000 IU/L is automatically diluted and the diluted sample redetermined. Unfortunately, employing a 1:200 fixed dilution can produce a working sample that contains an beta-hCG concentration that does not fall on a linear portion of the standard curve (<7.5 IU/L). This results in a calculated beta-hCG concentration (200 x observed value) that has high error (coefficient of variation up to 21.8%). Additionally, interfering substances in the reagents, which vary in quantity from lot to lot of reagents, further confound accurate beta-hCG determination by the system. Consequently, the Abbott IMx assay system cannot be used as recommended by the manufacturer for routine measurement of serum beta-hCG in the 900- to 2000-IU range. An alternate protocol employing at 1:10 dilution would allow a more accurate beta-hCG determination.

Autoanalysis↗

Sequence and structural analysis of surface protein antigen I/II (SpaA) of Streptococcus sobrinus.

Streptococcal antigen I/II or the surface protein antigen A (SpaA) of Streptococcus sobrinus is an adhesin which mediates binding of the organism to tooth surfaces. The complete sequence of the gene which encodes SpaA has been determined. The gene consists of 4,584 bp and encodes a protein of 1,528 amino acid residues. The deduced amino acid sequence shows extensive homology with those of the cell surface adhesins from Streptococcus mutans serotypes c and f and from Streptococcus sanguis. Structural analysis of the N-terminal region (residues 50 to 550), which is rich in alanine and includes four tandem repeats of an 82-residue sequence, suggests that it adopts an alpha-helical coiled-coil conformation. Cell surface hydrophobicity may be associated with this region. The C-terminal region is more conserved and includes two tandem repeats of a 39-residue proline-rich sequence. A further proline-rich sequence in this region is predicted to span the cell wall. Although a hydrophobic sequence is present in the C-terminal region, it appears to be too short to span the cell membrane. Anchoring of SpaA in the cell membrane may therefore require some form of posttranslational modification or association with another membrane protein.

Adhesins, Bacterial↗

Cloning of the amino terminal nucleotides of the antigen I/II of Streptococcus sobrinus and the immune responses to the corresponding synthetic peptides.

A portion of the antigen I/II (spaA, B, P1) gene of Streptococcus sobrinus 6715, containing the coding sequence for the amino terminal 684 amino acids of the protein, was cloned in bacteriophage lambda GT10. Selection was by immunological detection using a polyclonal antiserum to the antigen I/II from Strep. mutans. From the amino acid sequence, peptides were synthesized, 15 amino acids in length, that covered the entire sequence. In total, 260 synthetic peptides were synthesized and evaluated for their immunogenicity in Balb/C mice. Thirty-nine peptides were immunogenic, without carrier, and the antisera generated were tested for their ability to bind cells of Strep. mutans and Strep. sobrinus in a solid-phase assay. Antisera corresponding to peptides from five regions on the I/II molecule bound cells of both bacterial species. These peptides were then evaluated for their ability to stimulate in vitro murine lymphocyte proliferation, after in vivo immunization with Strep. sobrinus cells. Two of the peptides were capable of stimulating proliferation, as determined by incorporation of [3H]-thymidine into murine lymph node cells. The sequences of these 5 peptides were then compared to sequences found in the antigen I/II from Strep. mutans (Kelly et al., 1989). As expected, there was considerable homology between the cross-reactive peptides synthesized and the analogous region from Strep. mutans. This homology was not usually contiguous and suggests that the antibodies bind a face of antigen I/II that is in an alpha-helical conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗