Knowledge and attitudes of primary health care personnel concerning mental health problems in developing countries: a follow-up study

Within the context of a World Health Organization coordinated collaborative study health workers in six developing countries were assessed 18 months after their training for improvement in their knowledge and attitude towards mental health problems and their management. The approaches to training varied between study areas, but the degree of improvement following the training, was of equal magnitude in all countries. The training process has formalized the recognition by the health workers that treatment of mental health problems is an integral part of their work.     

Amplification and restriction endonuclease digestion of a large fragment of genes coding for rRNA as a rapid method for discrimination of closely related pathogenic bacteria.

By use of primers specific to conserved regions of the rRNA gene cluster, a discrete amplicon of approximately 5 kb was amplified by PCR from all 21 bacterial genera investigated. Subsequent endonuclease digestion of the PCR product with HaeIII distinguished between the three species of the human pathogen Francisella spp. on the one hand and four clinically relevant genomic groups of Acinetobacter spp. on the other hand. The described technique has the potential as a rapid method for discriminating between closely related species that are of clinical importance.     

A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p

The limb-girdle muscular dystrophies are a clinically and geneticallyheterogeneous group of disorders. We have ostudied two largeinbred families of different ethnic origin and excluded linkageto LGMD2 on chromosome 15q and SCARMD on chromosome 13. Proceedingto a genomic linkage search, we have now identified linkageto markers D2S134 and D2S136 on chromosome 2p (maximum lod score3.57 at zero recombination). The phenotype in the two familieswas similar, with onset in the pelvic girdle musculature inthe late teens and usually relatively slow progression. Thiswork Identifies a second locus for autosomal recessive limb-girdlemuscular dystrophy.     

Phenotype, activation and lymphokine secretion by gamma/delta T lymphocytes from schistosomiasis and carcinoma of the urinary bladder.

In humans the majority of the CD3+ T cells usually express an alpha/beta T cell receptor (TcR) and a minority express a gamma/delta TcR. The CD3+ TcR alpha/beta and CD3+ TcR gamma/delta cells from blood of the patients with schistosomiasis with carcinoma of the urinary bladder (SCB) were analyzed for phenotype, activation, secretion of interleukin 2 (IL 2). B cell growth factor (BCGF) and B cell differentiation factor (BCDF), as well as for autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reaction. Patients with SCB had a highly increased percentage of CD3+ TcR gamma/delta and a decreased percentage of CD3+ TcR alpha/beta T cells in their circulation. These CD3+ TcR gamma/delta T cells expressed the CD25 (IL 2 receptor), CD38, CD71 (transferrin receptor) and HLA-DR activation antigens at a higher intensity after in vitro stimulation with recombinant IL 2, phytohemagglutinin and soluble egg antigen (from Schistosoma haematobium). The SCB patients' CD3+ TcR gamma/delta T cells were highly deficient in secretion of IL 2 but produced highly elevated levels of BCGF and BCDF. On the contrary, both BCGF and BCDF activities of the CD3+ TcR alpha/beta T cells were decreased. Moreover, CD3+ TcR gamma/delta T cells demonstrated highly deficient AMLR and MLR activity. These observations suggest a possible role of CD3+ TcR gamma/delta T cells in the immune response and the disease pathogenesis in human schistosomiasis infections.     

Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis.

One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.     

Large B-cell lymphomas: fine-needle aspiration plays an important role in initial diagnosis of cases which are falsely negative by flow cytometry

Large B-cell lymphomas (LBCLs) have significant false-negative results when immunophenotyped by flow cytometry (FC). To clarify the role fine-needle aspiration (FNA) in reducing this false-negative rate, 28 cases ultimately diagnosed as LBCL that had FNA as part of the workup and a negative FC were identified. We examined their clinical and cytologic features, in comparison with cases of LBCL with FNAs that were positive by FC. In 24/28 FC-negative cases (86%) a cytologic diagnosis of suspicious or positive for malignancy was rendered. We conclude that cytologic analysis is more sensitive than FC in the diagnosis of malignancy in FNA of LBCL, particularly in aspirates with low cellularity and/or low viability. Examination of cytospin preparations of the actual material analyzed by FC may provide an indication that an FC result is falsely negative. It is important to recognize the potential of false-negativity by FC of LBCLs when interpreting FNAs with features suggesting lymphoma.     

Comparative genomic hybridization in ganglioneuroblastomas.

The ganglioneuroblastoma are rare lesions with widespread neuronal differentiation that have been classified as intermediate stages between neuroblastoma and ganglioneuroma. To identify overall chromosome aberrations in ganglioneuroblastoma, we performed comparative genomic hybridization. All of the five tumor samples were found to exhibit multiple gains involving different chromosomal regions. Chromosomal gains displayed by chromosomes and chromosome loci were 2p25 approximately pter (60%), 5p15.1 approximately p15.3 (60%), 7 (60%), 13q22 approximately q31 (60%), and 22 (60%), which were detected as minimal common regions in all five tumor samples. Chromosome 22 gain, which had not been reported in neuronal tumors before, and novel site 13q22 approximately q31 may be considered to play an important role in progression and differentiation of ganglioneuroblastoma.     

Differential infiltration by CD45RO and CD45RA subsets of T cells associated with human heart allograft rejection.

Subsets of T cells express different isoforms of the leukocyte common antigen CD45; those expressing the glycoprotein 220 isoform (CD45RA) have been characterized as naive in their response to antigens, and those expressing the glycoprotein 180 isoform (CD45RO) as memory T cells. The association between the rejection status of human cardiac allograft recipients and the relative infiltration of the CD45 subsets of both CD8+ and CD4+ T cells was examined using two-color immunohistological labeling techniques on 33 heart transplant biopsies, categorized by routine histological and clinical criteria as mild (requiring no treatment) or moderate (requiring antirejection therapy) rejection. Double-labeling was performed using pairs of monoclonal antibodies to define the following populations: CD4+ CD45RA+, CD4+ CD45RO+, CD8+ CD45RA+, and CD8+-CD45RO+. The number of cells per high-power field (HPF) for each of these cell subsets was counted in every biopsy. In cases with mild rejection, infiltration was predominant for CD4+ CD45RA+ cells (median = 5.0 cells/HPF) relative to CD4+ CD45RO+ (3.12 cells/HPF), CD8+ CD45RA+ (2.14 cells/HPF), and especially CD8+ CD45RO+ (1.22 cells/HPF) populations. In cases with moderate rejection, all four subpopulations increased but were essentially equivalent in intensity, such that in comparison to cases with mild rejection, the smallest increase was seen for CD4+ CD45RA+ cells (6.67 cells/HPF, P < 0.09) and the greatest for CD8+ CD45RO+ cells (7.00 cells/HPF, P < 0.002). A majority of CD8 cells expressed CD45RA in 14 of 16 (88%) cases of mild rejection compared to only 2 of 17 cases of moderate rejection. Moreover, the ratio of CD45RO+ to CD45RA+ cells in each biopsy was higher in moderate versus mild rejection for both CD4 (median ratios = 1.13 versus 0.68, respectively; P < 0.008) and CD8 (1.43 versus 0.58, respectively; P < 0.005) subsets. A majority of T cells expressed CD45RO in cases of moderate rejection (11 of 14 or 79%), compared to only 1 of 13 (8%) cases of mild rejection. These findings indicate that during generally self-limited mild acute cardiac allograft rejection there is a predominance of naive CD45RA+ T cells, especially of the CD4 phenotype, whereas during moderate rejection there is a significant shift toward activated CD45RO+ T cells, especially in the CD8 population.     

Adherence to and damage of endothelial cells by Cryptococcus neoformans in vitro: role of the capsule.

Escape from the intravascular compartment is likely a critical step in the development of hematogenously disseminated cryptococcal infections, such as meningitis. The capsule of Cryptococcus neoformans is considered to be a virulence factor because of its antiphagocytic properties. To further investigate the role of the capsule in escape from the intravascular compartment, we used isogenic strain pairs, an acapsular mutant, and an encapsulated clinical isolate to determine the effects of the capsule of C. neoformans on adherence to, phagocytosis by, and damage of endothelial cells in vitro. Acapsular C. neoformans adhered significantly more to endothelial cells and caused greater endothelial cell injury than did encapsulated organisms. Coating of an acapsular strain with cryptococcal glucuronoxylomannan decreased both adherence to and damage of endothelial cells by 61.7% +/- 9.1% and 76.6% +/- 10.2%, respectively. Transmission electron microscopy demonstrated internalization of acapsular, but not encapsulated, organisms by endothelial cells. Internalization of an acapsular strain occurred through endothelial cell phagocytosis and was inhibited by cytochalasin D. Phagocytosis required a heat-labile serum factor, probably complement. These results suggest that acapsular or poorly encapsulated C. neoformans may be the form(s) that escapes from the vasculature during initiation of hematogenously disseminated disease.