Pulmonary diseases in patients infected with the human immunodeficiency virus in Zimbabwe, Central Africa

During the 11 month period up to 30 September 1987, 37 patients (26 male, 11 female, mean age 27 years) with respiratory symptoms who were human immunodeficiency virus (HIV) positive, were studied prospectively on 40 occasions to determine the cause of any pulmonary complications. HIV was heterosexually transmitted. Predominant symptoms were cough (89%), fever (89%), weight loss (83%), and dyspnoea (60%). Transnasal fibre-optic bronchoscopy (with bronchoalveolar lavage, bronchial brushings and transbronchial lung biopsies) was performed on 35 patients, twice on 3 patients. 'Tru-cut' lung biopsies were obtained from 2 patients who died before bronchoscopy. Pulmonary tuberculosis was the commonest disease, being found in one-third of the patients (12 of 37). Mycobacterium tuberculosis was cultured from 4; the remainder of the plates were contaminated. Pneumocystis carinii was present in 8 patients: as the sole pathogen in 3, with Streptococcus pneumoniae in 4, Staphylococcus aureus in 2, and one also had tuberculous lymphadenitis. Endobronchial Kaposi's sarcoma was seen in 6 of 7 patients with skin nodules. Bacterial pathogens isolated included Staph. aureus (5), S. pneumoniae (5), Klebsiella pneumoniae (2), Haemophilus influenzae (2), H. parainfluenzae (1) and Pseudomonas aeruginosa (1). Invading Aspergillus fumigatus was diagnosed by lung biopsy in one. No diagnosis was reached for 8 patients. It is concluded that in Central Africa pulmonary complications in AIDS patients are similar to those in Europe and North America but the incidence of different pathogens depends on the prevalence of pathogens in the community. M. tuberculosis is probably the commonest pathogen. This study has confirmed that P. carinii pneumonia does occur, but occurs less frequently.     

Tick infestations on Zebu cattle in western Kenya: host resistance to Rhipicephalus appendiculatus (Acari: Ixodidae)

Tick-susceptible Friesian steers were used as bait animals to assess the availability of adult Rhipicephalus appendiculatus Neumann on the pasture. Assuming that initial gross pickup rates of ticks by cattle were similar, the numbers of female ticks that attached and the numbers that subsequently fed to maturity on individual cattle were compared based on data obtained from bait animals. The proportion of successful attachments on high-resistance (HR) cattle (0.30) was significantly less than that on the low-resistance (LR) animals (0.51). Similarly, the proportion of attached ticks that fed to maturity also was significantly lower on HR animals (0.15) than on LR animals (0.33). Female survival was calculated as the product of these two parameters. On the HR cattle, female survival (0.05) was significantly less than on LR (0.18). About 12% of the cattle had low resistance, and up to 73% of the females survived on them. These animals were responsible for much of the tick multiplication in the field population.     

Molecular pathology of NEU1 gene in sialidosis

Lysosomal sialidase (EC 3.2.1.18) has a dual physiological function; it participates in intralysosomal catabolism of sialylated glycoconjugates and is involved in cellular immune response. Mutations in the sialidase gene NEU1, located on chromosome 6p21.3, result in autosomal recessive disorder, sialidosis, which is characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides. Sialidosis type I is a milder, late-onset, normosomatic form of the disorder. Type I patients develop visual defects, myoclonus syndrome, cherry-red macular spots, ataxia, hyperreflexia, and seizures. The severe early-onset form, sialidosis type II, is also associated with dysostosis multiplex, Hurler-like phenotype, mental retardation, and hepatosplenomegaly. We summarize information on the 34 unique mutations determined so far in the sialidase gene, including four novel missense and one novel nonsense mutations found in two Czech and two French sialidosis patients. The analysis of sialidase mutations in sialidosis revealed considerable molecular heterogeneity, reflecting the diversity of clinical phenotypes that make molecular diagnosis difficult. The majority of sialidosis patients have had missense mutations, many of which have been expressed; their effects on activity, stability, intracellular localization, and supramolecular organization of sialidase were studied. A structural model of sialidase allowed us to localize mutations in the sialidase molecule and to predict their impact on the tertiary structure and biochemical properties of the enzyme.     

The effect of surface sugars on liposomes in immunopotentiation

The effect of surface sugars of liposomes on the immunological responses to entrapped antigen has been investigated. alpha-Mannose and beta-galactose were grafted on the surface of liposomes containing lysozyme by covalent coupling of p-aminophenyl-D-glycosides to phosphatidyl ethanolamine liposomes using glutaraldehyde. Subcutaneous administration of antigen entrapped in beta-galactose liposomes stimulated an antibody response comparable to that elicited by sugar-free neutral liposomes. However, alpha-mannose bearing liposomes with entrapped lysozyme elicited an immune response similar to that induced by lysozyme in saline. Based on these observations it is suggested that alpha-mannose liposomes, that are specifically recognized by macrophages, are taken up rapidly by receptor mediated endocytosis and that the entrapped antigen is then rapidly degraded, resulting in low antibody production.     

Chromosome 22q11.2 deletion and phenotypic features in 30 patients with conotruncal heart defects

This report describes the dysmorphic features and frequency of 22q11.2 deletion (del22q11) in 30 Turkish patients with conotruncal heart defects (CTHDs). Fluorescence in situ hybridization (FISH) analysis revealed deletions in the 22q11.2 region in nine (30%) individuals. The CTHDs in this group were tetralogy of Fallot (four cases), double-outlet right ventricle (DORV) (two cases), transposition of great arteries (two cases), and ventricular septal defect (VSD) associated with other CTHDs (one case). The frequency of del22q11 in the study group was relatively high because many of the patients with dysmorphic findings also had cardiac anomalies involving the pulmonary artery, ductus arteriosus, or the aortic arch and its main branches. Twenty of the 30 patients exhibited several dysmorphic findings. Two of the nine patients with del22q11 exhibited no apparent dysmorphic features other than sacral dimple. Interestingly, one of the patients with del22q11 had a phenotypic appearance similar to that seen in oculo-auriculo-vertebral spectrum (OAVS). This individual had left microtia, atresia of the external meatus, mandibular asymmetry, and peripheral facial nerve paralysis. His mental development was normal and there were no abnormalities on ophthalmological examination. The CTHDs in this patient were situs inversus dextrocardia, DORV, pulmonary stenosis, and VSD. Radiographs of this patient showed platybasia, complete fusion of C2-C3, and posterior fusion of the T1-T2 vertebrae. This particular case indicates that the phenotypic features of del22q11 and OAVS may overlap.     

Matrix Metalloproteinase and Cytokine Profiles in Monocytes over the Course of Stroke

Stroke is a common cause of death and disability in our society. Stroke is associated with changes in immune responses within the central nervous system as well as systemically. The cells contributing to such changes as well as the factors contributing to formation of the inflammatory infiltrate observed in stroke remain to be clarified. In this study, blood monocytes and corresponding mononuclear cells (MNC) were separated and examined in parallel within 4 days and 1–3 months after onset of ischemic stroke. Numbers of TNF--, IL-12-, IL-6-, and IL-10-secreting cells and of cells expressing mRNA for matrix metalloproteinase (MMP)-1, -2, -7, -9 and tissue inhibitor of MMP (TIMP)-1 were studied. The TNF--, IL-12-, and IL-6-secreting monocytes and MNC were elevated during the acute phase compared to healthy controls. Such differences were not observed when stroke patients were examined during convalescence. The IL-10-secreting monocytes did not change over the course of stroke. Levels of monocytes expressing MMP-1, MMP-7 and TIMP-1 mRNA were elevated in the acute phase of stroke patients compared to convalescence and healthy controls, as were levels of MMP-1, -2, -7, -9 and TIMP-1 mRNA expressing blood MNC. The MMP-2 and -9 activity as measured by zymography also was higher in MNC supernatants in the acute phase of stroke compared to convalescence. The high levels of proinflammatory cytokines and MMPs in blood monocytes and MNC further demonstrate the presence of systemic aberrations in the acute phase of stroke. Such changes may contribute to the influx of blood-borne cells into the ischemic lesions during the acute phase of stroke.     

Reversal of the CD4(+)/CD8(+) T-cell ratio in lymph node cells upon in vitro mitogenic stimulation by highly purified, water-soluble S3-S4 dimer of pertussis toxin

Pertussis toxin (PT), a holomer consisting of a catalytic S1 subunit and a B oligomer composed of S2-S4 and S3-S4 dimers, held together by the S5 subunit, exerts profound effects on immune cells, including T-cell mitogenicity. While the mitogenic activity of PT was shown to reside fully within the B oligomer, it could not be assigned to any particular B-oligomer component. In this study, we purified the S3-S4 dimer to homogeneity under conditions propitious to maintenance of the native conformation. In contrast to previous reports which suggested that both S3-S4 and S2-S4 dimers are necessary for mitogenic activity, our preparation of the highly purified S3-S4 dimer was as strongly mitogenic as the B oligomer, suggesting that the S3-S4 dimer accounts for the mitogenic activity of the B oligomer. Moreover, in vitro stimulation of naive lymphocytes by the S3-S4 dimer resulted in reversal of the normal CD4(+)/CD8(+) T-cell ratio from approximately 2:1 to 1:2. The reversal of the CD4(+)/CD8(+) T-cell ratio is unlikely to be due to preferential apoptosis-necrosis of CD4(+) T cells, as indicated by fluorescence-activated cell sorter analysis of annexin-stained T-cell subsets, or to preferential stimulation of CD8(+) T cells. The mechanism underlying the reversal requires further investigation. Nevertheless, the data presented indicate that the S3-S4 dimer may have potential use in the context of diseases amenable to immunological modulation.