Pneumocystis carinii f. sp. hominis is not infectious for SCID mice

The infectious power of Pneumocystis carinii f. sp. hominis was explored by inoculating SCID mice intranasally with either P. carinii f. sp. hominis or P. carinii f. sp. muris isolates. Only mice inoculated with mouse parasites developed Pneumocystis pneumonia, as assessed by microscopy and PCR. These results suggest that humans do not contract pneumocystosis from animals.     

Teaching approaches that reflect and promote professionalism.

The teaching and cultivation of professionalism have long been part of medical education and have had recent special emphasis because professionalism has been identified as a core competency by the Accreditation Council for Graduate Medical Education. The author focuses on two complementary teaching initiatives that contribute to the development of professionalism in the academic environment: a resident-as-teacher program and an approach to faculty bedside teaching that mirrors and extends the lessons of the resident-as-teacher effort. These have been implemented and refined over the previous 15 years by the author and his colleagues at Mount Auburn Hospital in Cambridge, Massachusetts. The commitment to the development and refinement of residents' teaching skills serves to promulgate the fundamental elements of professionalism, with emphasis on caring and the educational well-being of the team. The author describes the elements and benefits of these approaches and shows how they can foster the development of professionalism in graduate medical education.     

Analysis of Dystrophin Gene Deletions by Multiplex PCR in Moroccan Patients

Duchenne and Becker muscular dystrophy (DMD and BMD) are X-linked diseases resulting from a defect in the dystrophin gene located on Xp21. DMD is the most frequent neuromuscular disease in humans (1/3500 male newborn). Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. We have analyzed DNA from 72 Moroccan patients with DMD/BMD using the multiplex polymerase chain reaction (PCR) to screen for exon deletions within the dystrophin gene, and to estimate the frequency of these abnormalities. We found dystrophin gene deletions in 37 cases. Therefore the frequency in Moroccan DMD/BMD patients is about 51.3%. All deletions were clustered in the two known hot-spots regions, and in 81% of cases deletions were detected in the region from exon 43 to exon 52. These findings are comparable to those reported in other studies. It is important to note that in our population, we can first search for deletions of DMD gene in the most frequently deleted exons determined by this study. This may facilitate the molecular diagnosis of DMD and BMD in our country.     

Subtotal amelia in a child with autosomal recessive hypohidrotic ectodermal dysplasia

We report an inbred Tunisian family, in which the proband manifested signs of hypohidrotic ectodermal dysplasia, subtotal amelia, scoliosis and left renal agenesis. Two other family members had the full clinical criteria of hypohidrotic ectodermal dysplasia, characterized by deficient sweat glands, hypodontia, hypoplasia of the mucous glands, and fine hair. Nine family subjects had variable clinical expression of the disorder.     

T lymphocytemediated cytotoxicity in hbsag-positive liver disease

It has been suggested that cellular immune responses to the hepatitis B virus are of importance in the production of liver cell damage in both acute and chronic hepatitis. An assay has now been developed which detects lymphocytes cytotoxic for target cells coated with the hepatitis B surface antigen (HBsAg). The reaction could be blocked by prolonged pre-incubation of lymphocytes with highly purified HBsAg and studies with lymphocyte subpopulations have shown that T lymphocytes were the principle effector cells.

When lymphocytes from twenty-three patients with acute hepatitis were used, cytotoxic T cells were demonstrable during the recovery phase, but not in the first 3 weeks of the illness. However, when these same lymphocytes were extensively washed, cytotoxicity was then detected in all the patients, even at the time of presentation. In patients with HBsAg-positive chronic liver disease the results with the standard assay were largely within the normal range, but again with extensive lymphocyte washing cytotoxicity was detected in all of the patients with untreated chronic active hepatitis and in five out of six with more minor histological lesions. The results in five carriers with normal liver histology were completely different, cytotoxicity remaining undetectable even after the extensive washing procedure.

The results suggest that blocking factors, possibly antigen or antigen–antibody complexes, could be interfering with the detection of sensitized T cells in patients with acute and chronic hepatitis, but that there is a true absence of sensitization to HBsAg in healthy carriers with normal liver histology.

     

Mitochondrial DNA Heterogeneity in Tunisian Berbers

Berbers live in groups scattered across North Africa whose origins and genetic relationships with their neighbours are not well established. The first hypervariable segment of the mitochondrial DNA (mtDNA) control region was sequenced in a total of 155 individuals from three Tunisian Berber groups and compared to other North Africans. The mtDNA lineages found belong to a common set of mtDNA haplogroups already described in North Africa. Besides the autochthonous North African U6 haplogroup, a group of L3 lineages characterized by the transition at position 16041 seems to be restricted to North Africans, suggesting that an expansion of this group of lineages took place around 10500 years ago in North Africa, and spread to neighbouring populations. Principal components and the coordinate analyses show that some Berber groups (the Tuareg, the Mozabite, and the Chenini‐Douiret) are outliers within the North African genetic landscape. This outlier position is consistent with an isolation process followed by genetic drift in haplotype frequencies, and with the high heterogeneity displayed by Berbers compared to Arab samples as shown in the AMOVA. Despite this Berber heterogeneity, no significant differences were found between Berber and Arab samples, suggesting that the Arabization was mainly a cultural process rather than a demographic replacement.     

Contribution of a typing method based on IS256 probing of SmaI-digested cellular DNA to discrimination of European phage type 77 methicillin-resistant Staphylococcus aureus strains.

The incidence of infections with phage type 77 methicillin-resistant Staphylococcus aureus (MRSA) strains increased in France in 1987. These strains are widespread in numerous European hospitals. The SmaI restriction profiles of total DNA extracted from 74 phage type 77 MRSA strains isolated from 1987 to 1994 in 10 hospitals in eight European cities (in France, Belgium, and Spain) were analyzed. Hybridization with a probe containing a 468-bp DNA fragment from within the transposase gene of the insertion sequence IS256 was also examined. Forty-three SmaI profiles were detected. Twenty major genotypes were identified, and each genotype contained strains with the same profile or profiles which differed by no more than three bands. Strains isolated in different countries and at several-year intervals were often grouped within the same genotype. A larger number of genotypes could be discriminated by analysis of the patterns of hybridization with the IS256 probe. SmaI restriction fragments with the same apparent electrophoretic mobility could, in some cases, be distinguished by the presence or the absence of nucleotide sequences hybridizing with IS256. The strains that grouped within the same genotype after hybridization with IS256 were mostly those isolated in the same hospital and at less than 12-month intervals. Consequently, the IS256 probe that we used improved restriction profile analysis for discrimination between the intrahospital, outbreak-related phage type 77 MRSA strains and the endemic strains disseminated in various cities and countries.     

Changes in the level of antioxidants in the blood from mice infected with<Emphasis Type="Italic"> Trichinella spiralis</Emphasis>

The biological reaction caused by oxygen-derived free radicals at the molecular and cellular levels involves many different biochemical components which can be directly damaged by oxidizing radicals. As such a reaction may lead to pathological processes, defence mechanisms have evolved to limit the rate of free radical production. These mechanisms employ low-molecular-weight non-enzymatic antioxidants and antioxidant enzymes which are inducible by oxidant stress. In this study, the activity of two antioxidant enzymes, superoxide dismutase (EC 1.15.1.1) and glutathione peroxidase (EC 1.11.1.9), and the level of non-enzymatic antioxidants (total antioxidant status) in the blood from mice infected with Trichinella spiralis was examined. We observed a statistically significant, up to above twofold increase (relative to the control value in uninfected mice) in the level of both enzymes as well as in the total antioxidant status. An intensification of antioxidant processes during trichinellosis could be related to the presence of T. spiralis larvae, which may induce phagocytes to generate free radicals. Our research shows that the maximum growth in antioxidant activity in the blood appears during the period of the greatest muscle damage caused by T. spiralis infection at 3–7 weeks post-infection.     

Sequence-Based analysis of the HLA-DRB1 polymorphism in Metalsa Berber and Chaouya Arabic-speaking groups from Morocco

To examine the genetic diversity in Morocco, the polymorphism at the HLA-DRB1 locus was investigated in two populations: the Metalsa group consisting of Berbers from north Morocco (who speak the Tarifit language and live in the Nador area), and the Chaouya group who are Arabic-speaking people from west Morocco (Atlantic coast) living in the Settat area. The DRB1 alleles of 197 healthy unrelated individuals were identified by direct DNA sequencing of exon 2 using fluorescently-labeled primers. A total of 28 and 29 alleles at DRB1 locus were identified in the Metalsa and Chaouya groups, respectively. The most frequent alleles in the Metalsa group are DRB1*03011 (20.2%), DRB1*0701 (12.12%), and DRB1*1302 (11.11%). In the Chaouya group, DRB1*0701 (16.33%), DRB1*15011 (12.76%), and DRB1*03011 (11.73%) are most common. Each population exhibits some specific variants and some uncommon alleles. The frequency of the DRB1*03011 allele differs significantly between the two populations (p = 0.0311). The DRB1 frequency distributions in the two groups suggest the effects of balancing selection. The interpopulation analysis highlighted a strong relatedness, based on genetic distances, between the two Moroccan groups and the other north Africans (the Moroccans from El Jadida area, Moroccan Souss Berbers, Algerians, and Tunisians), and to a lesser extent with the Iberians, French, and Ethiopians.