Synthesis and immunological characterization of a 134-mer synthetic peptide corresponding to the N-terminal half of the HIV-1 nucleoprotein,p24

A 134-mer peptide corresponding to the N-terminal sequence of p24 (residues 146–279 of the gag gene product of the LAV strain) was chemically synthesized using highly optimised protocols on an ABI 430A synthesizer. The crude peptide was obtained by treating the peptide-resin with HF, then purified by a combination of size exclusion and RP-HPLC. One hundred milligram of 90% pure 134-mer can be obtained within a month. Both mice and rabbit polyclonal antisera raised against a commercial preparation of recombinant p24, and a pooled sera from HIV-1 infected individuals reacted strongly with the 134-mer peptide in ELISA. Both mice and rabbits immunized with the free peptide emulsified in Freund's complete adjuvant generated strong anti-peptide and anti-p24 antibody responses as judged by immunoblots and ELISAs. Immunodominant epitopes were mapped to residues 201–227 (LKETINEEAAEWDRVHPVHAGPIAPG). These B-cell epitopes had previously been identified by mouse monoclonal antibodies raised against HIV-1 virus or gag gene products. Furthermore, murine T-cell lines generated against the 134-mer peptide were found to respond to two short peptides, P24B (residues 195–215) and P24D1 (residues 268–279). These two T-cell epitopes were previously reported as human helper T-cell and CTL epitopes, respectively. These results clearly indicate that the synthetic 134-mer peptide could elicit both T- and B-cell responses to HIV-1 similar to those obtained with the natural viral gag protein, and could be useful for the development of a synthetic HIV vaccine     

Preliminary Toxicity Profile of Arotinoids SMR-2 and SMR-6 in Male B6D2F1 Mice

Preliminary Toxicity Profile of Arotinoids SMR-2 and SMR-6 inMale B6D2F1 Mice. LINDA-MOOD, C, III, GILES, H. D., AND HILL,D. L. (1987). Fundam. Appl. Toxicol. 8, 517–530. Arotinoids,which are analogs of retinoic acid (RA) and retinol (RO) withthe carbon skeleton in a rigid conformation, have more favorabletherapeutic indices relative to all-transRA and al-trans-RO.The purpose of this investigation was to obtain preliminaryin vivo toxicity data on SMR-2 (analog of RO) and SMR-6 (analogof RA), arotinoids with promising activity (ED50's of 20 x 10^–11and 5 x 10^–11 m, respectively; ED50 of RA = 1 x 10^–11m) for reversal of keratinization in tracheal organ culture.A preliminary toxicity study was conducted in male B6D2F1 micewith gavage of retinoids in corn oil (0.01, 0.05, and 0.1 mg/kg/dayof SMR-2 or SMR-6; 1, 5, and 10 mg/kg/day of RA as referencecontrol). Due to lack of toxicity, each dose level for SMR-2and SMR-6 was increased by 4-fold on Day 29 of dosing. The studywas terminated on Day 57. Hypervitaminosis A (weight loss, alopecia,skin scaling, and bone thinning) was induced in the mid- andhigh-dose SMR groups; weight-gain depression was predominantin the high-dose RA group. The SMR compounds were approximately100-fold more toxic, based on weight loss, than RA. In the SMRdose groups with hypervitaminosis A, white blood cell countswere elevated 2- to 4-fold; and there were microscopic lesionsin skin, testes, epididymis, bone, thymus, bone marrow, peripherallymph nodes, spleen, stomach, adrenal, and pituitary. The leuko-cytosiswas attributed to leukopoiesis in spleen and bone marrow, whichmay be due to either a direct effect and/or a secondary responseto a subacute inflammatory reaction in skin. Only peripherallymph node hyperplasia was observed in SMR-2 and RA low-dosegroups. Enlarged thymus, lymph node hyperplasia, leukopoiesisin spleen and bone marrow, elevated alkaline phosphatase withbone hypertrophy, and testicular degeneration were observedin the mid-dose RA group. The results indicate that immune stimulationmay be a primary early response to retinoids and that skin,leukopoietic tissues, reproductive organs, stomach, and boneare primary targets for retinoid toxicity.     

Haemodialysis decreases finger pressures independent of artificial kidney blood flow

Background: During haemodialysis, some patients experience intensification of symptoms of haemodialysis access‐induced distal ischaemia. Aim of this study is to compare the effects of two different regimens of arterial blood flow in patients with an arteriovenous access. Methods: A questionnaire identified 10 patients that subjectively experienced ischaemic symptoms during haemodialysis. Systolic blood pressure, heart rate, finger pressure (P_dig), finger temperature (T_dig), oxygen saturation and ischaemic scores were monitored during two different arterial blood flow dialysis sessions. Results: Before dialysis, P_dig and T_dig of the arteriovenous access hand were significantly lower compared with the other hand. Haemodialysis induced a drop of P_dig in both hands. All changes in P_dig occurred independent of the artificial kidney's blood flow level. Conclusion: Systemic hypotension following onset of haemodialysis further intensifies an already diminished hand perfusion. Measures preventing dialytic hypotension will likely attenuate symptoms associated with haemodialysis access‐induced distal ischaemia during haemodialysis.     

Listening as a method of addressing psychological distress

Aims  This paper discusses the values of therapeutic listening and ways that emotional difficulties can impact palliative nurses' abilities to provide psychological care.
Background  Recent literature indicates that providing psychological care can burden some healthcare professionals including nurses; who may lack the necessary competencies or organizational resources to carry out their roles.
Evaluation  References drawn from the databases: all EBM reviews, BRITISH NURSING INDEX, CINAHL, PSYCH INFO and MEDLINE and EMBASE are discussed.
Key issues  Psychological care is considered critical to providing holistic care. Yet the literature suggests engaging in such work makes emotional demands on the professionals attempting to carry it out and is associated with psychological difficulties including burnout.
Conclusion  Clinical supervision can help reduce the distress caused by emotionally charged situations. Thoughtful clinical supervision can also contribute to safe and effective health care.
Implications for Nursing Management  Nursing would benefit from understanding more about the effects on healthcare professionals of repeated exposure to emotionally charged situations and benefits that clinical supervision can offer to health care.     

Synthesis and receptor binding affinity of both E-and Z-dehydro-phenylaline4 enkephalins*

The dehydrophenylalanine⁴-enkephalin having the E-configuration (Δ^EPhe; phenyl and C = O, cis) was prepared by photoisomerization of the Z-isomer with 3100 Å light, followed by reversed-phase HPLC separation of the resulting mixture of the Z- and E-isomers. In the radioligand receptor binding assays, the E-isomer of [D-Ala², ΔPhe⁴, Leu⁵]enkephalin exhibited an extremely diminished affinity as compared with the Z-isomer, namely 150–260-fold loss of affinity for the delta and mu opiate receptors. The results indicate that the interrelationship of the Tyr¹ and Phe⁴ residues in the enkephalin molecule seems to be of great importance in receptor recognition.     

The role of weight for age and disease stage in poor psychomotor outcome of HIV-infected children in Kilifi, Kenya

Aim  We aimed to investigate the contribution of disease stage and weight for age to the variability in psychomotor outcome observed among children with human immunodeficiency virus (HIV) infection.
Method  This cross-sectional study involved 48 Kenyan children (20 females, 28 males) aged 6 to 35 months (mean 19.9mo SD 8.9) exposed prenatally to HIV. Two subgroups of HIV-exposed children were seen: those who were HIV-infected and those who were uninfected. The reference population was composed of 319 children (159 females, 160 males) aged 6–35 months, (mean age = 19 months, SD=8.43) randomly selected from the community. Disease stage varied from stage 1 to stage 3, reflecting progression from primary HIV infection to advanced HIV infection and acquired immune deficiency syndrome. A locally developed and validated measure, the Kilifi Developmental Inventory, was used to assess psychomotor development.
Result  Using age-corrected psychomotor scores, a significant main effect of HIV status was observed ( F _(2,38.01)=7.89, p <0.001). Children in the HIV-infected group had lower mean psychomotor scores than the HIV-exposed children and the reference group. In the HIV-infected group, disease stage was a negative predictor and weight for age a positive predictor of psychomotor outcome.
Interpretation  Weight for age and disease stage provide viable, easily measurable benchmarks to specify when frequent developmental monitoring and psychomotor rehabilitation are required. Nutritional intervention and other measures aimed at slowing disease progression may delay the onset and severity of psychomotor impairment in the paediatric HIV population in Africa.     

Endothelial cell dysfunction in homocystinuria

Abstract. This report describes the isolation and culture of venous endothelial cells from the umbilical cord of an obligate heterozygote for homocystinuria. The effect of different sulphur-containing amino acids on the viability and function of these cells was studied and compared with cultured normal endothelial cells. When endothelial cells were cultured in the presence of methionine (10 mmol/l) or homocystine (10 mmol/l), differences occurred between the viability and function of the heterozygote and normal cells in terms of ⁵¹Cr release and ability to prevent platelet adherence. The Cr release corrected for spontaneous release increases for the heterozygote cells after incubation for 21 h in the presence of methionine to 81.3% (control cells, range: 0–23.3%, n = 5) and in the presence of homocystine to 141% (control cells, range: 13.5–55.2%, n = 5). The total number of platelets that adhere to confluent monolayers increases for heterozygote cells cultured in the presence of methionine to 0.98 ± 10⁷ platelets cm^-2 (normal cells, range: 0.56–0.72 ± 10⁷ platelets cm^-2) and in the presence of homocystine to 1.41 ± 10⁷ platelets cm^-2 (normal cells, range: 0.94–1±06 ± 10⁷ platelets cm^-2). Both normal and control cells were sensitive to homocysteine. This study indicates for the first time what vascular endothelial cells, derived from an obligate heterozygote, are (partly) deficient in cysthathionine synthase and are more susceptible to methionine- and homocystine-mediated injury than normal endothelial cells. Consequently, in homocystinuria, due to dysfunction of the endothelial cells, toxic sulphur-containing amino acids may accumulate in these cells, causing injury of these cells.