Selection of Single Nucleotide Polymorphisms for Association Studies in Candidate Genes

Comparison of polymorphic sites such as single nucleotide polymorphisms (SNPs) within a gene between cases and controls may be useful for establishing a role of this gene in disease susceptibility. The approach includes two steps: the first step is the discovery of the different SNPs within the candidate gene and the second step is the association testing per se that can be done on the entire set of sites discovered or on a subset of these sites only. Selecting a subset of sites may increase the power to detect the association with the candidate gene since a smaller number of tests would then be performed. We proposed a strategy to select sites within a candidate gene and applied it on the Genetic Analysis Workshop 12 candidate gene data. Using these selected sites, we detected an association with candidate genes 1 and 6. © 2001 Wiley‐Liss, Inc.     

Coping with mild inflammatory catamenial acne

BACKGROUND: Acne is a multifactorial disease exhibiting distinct clinical presentations. Among them, the catamenial type is a matter of concern for young women. Some oral contraceptives may help without, however, clearing the skin condition. AIM: The present open study aimed at evaluating the effect of overnight applications of a paste made of petrolatum,15% zinc oxide and 0.25% miconazole nitrate. METHOD: The split-face trial was conducted in 35 women. A non-medicated cream was used as control. Clinical evaluations and biometrological assessments on cyanoacrylate follicular biopsies were performed monthly for 3 months. Comedometry and the density in autofluorescent follicular casts were used as analytical parameters. In addition, the five most severe cases at inclusion were tested at the completion of the study for follicular bacterial viability using dual flow cytometry. RESULTS: Compared with baseline and to the control hemi-face, the medicated paste brought significant improvement of acne. The number of papules and their redness were reduced beginning with the first treatment phase. A reduction in the follicular fluorescence was yielded beginning with the second treatment phase. The ratios between injured and dead bacteria, on the one hand, and live bacteria, on the other hand were significantly increased at completion of the study. CONCLUSION: A miconazole paste applied for 1 week at the end of the ovarian cycle has a beneficial effect on catamenial acne.     

Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: 17 cases. Report from the EBMTG

Allogeneic bone marrow transplantation (BMT) was performed in 17 patients with chronic lymphocytic leukemia (CLL): 15 resistant and two untreated forms. There were 12 males and five females with a mean age of 40 years (32-49). The conditioning regimens and graft-versus-host disease (GVHD) prophylaxis varied. Successful engraftment was obtained in 15 evaluable cases. Lymphocytosis and clinical symptoms subsided in all but one case. All 15 evaluable patients developed acute GVHD. Among the 17 patients grafted, one early death was observed at the 15th day post-BMT, and one refractory patient died 2 months after BMT. Of the remaining 15 patients in complete remission (CR), four died from GVHD, hemorrhage and graft failure, and two relapsed at 7 and 54 months after BMT and died. Nine patients are alive in CR with a mean follow-up of 25.6 months (4-48). Chimerism was complete in eight patients and partial in the two T cell-depleted cases. In one case, an immunoglobulin gene rearrangement study showed no residual disease. These results suggest that allogenic BMT might be an alternative and possible curative therapy for refractory CLL in young patients when performed relatively early in the disease.     

Propriospinal myoclonus: utility of magnetic resonance diffusion tensor imaging and fiber tracking.

Propriospinal myoclonus (PSM) is a rare movement disorder characterized by involuntary spinal-generated muscular jerks that spread rostrally and caudally to other spinally innervated muscles. Most patients have no clear etiology, and conventional MRI of the spinal cord is generally normal. Here we report the use of magnetic resonance diffusion tensor imaging (DTI) and fiber tracking to detect tract-specific abnormalities in a patient with propriospinal myoclonus. As the patient had the fragile-X premutation and antithyroid antibodies, spinal cord DTI abnormalities may be related to these conditions. Tract-specific analysis may provide new insights into the pathophysiology of propriospinal myoclonus.     

Lack of association of angiotensin I-converting enzyme gene polymorphism and premature myocardial infarction in Mauritian Indians

Eighty-five young Mauritian Indians, male survivors of premature myocardial infarction (MI) and thus belonging to a high risk group, were compared with 108 stringently selected controls for a possible association between premature MI and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group and 0.43 in the control group, and thus no association between I/D polymorphism of ACE with susceptibility to early-onset MI was found in this population group. Other gene components of the renin-angiotensin system and lipid metabolism need to be explored to understand the genetic factors involved in causing MI at an early age.     

A mammary gland adenomyoepithelioma in a C57BL/6 mouse

Mammary gland adenomyoepitheliomas are benign complex mammary gland tumors composed of neoplastic cells of epithelial and myoepithelial origins, described in many species (humans, dogs, cats, rats) and rarely in mice. We report here an adenomyoepithelioma in a C57BL/6 female mouse. Histologically, tubes and cords formed by neoplastic epithelial cells were separated by bundles of neoplastic myoepithelial cells in a clear and partially mucinous matrix. The tumor displayed characteristics of a benign neoplastic proliferation with a compressive growth pattern, and moderate cellular pleomorphism and mitotic index. At immunohistochemistry, the epithelial cells were strongly cytokeratin positive; the myoepithelial cells were weakly cytokeratin positive and strongly smooth muscle actin positive. This is to our knowledge, the first report of a mammary gland adenomyoepithelioma in a C57BL/6 mouse.     

Chronic myeloid leukemia with unusual variant Ph translocation (22;22)(q11;q13). Two cases with chimeric BCR-ABL transcripts

We studied two cases of chronic myelogenous leukemia (CML) with unusual variant Philadelphia (Ph) translocation (22;22)(q11;q13). Southern blot analysis showed a chromosomal break in the BCR gene within the 5.8-kilobase (kb) breakpoint cluster region (bcr), between bcr exons 2 and 3 and between bcr exons 3 and 4, respectively. Chimeric bcr-abl mRNA was detected using polymerase chain reaction (PCR) which amplified, according to the respective bcr breakpoints, bcr exon 2-abl exon II and bcr exon 3-abl exon II junction products. These results further support the involvement, even when not cytogenetically detectable, of the 9q34 chromosomal region in all variant Ph translocations and that BCR-ABL gene fusion products are causally involved in the development of Ph positive CML.     

Preservation of the pattern of tyrosine phosphorylation in human neutrophil lysates. II. A sequential lysis protocol for the analysis of tyrosine phosphorylation-dependent signalling

In stimulated neutrophils, the majority of tyrosine phosphorylated proteins are concentrated in Triton X-100 or NP-40 insoluble fractions. Most immunobiochemical studies, whose objective is to study the functional relevance of tyrosine phosphorylation are, however, performed using the supernatants of cells lysed in non-ionic detergent-containing buffers (RIPA lysis buffers). This observation prompted us to develop an alternative lysis protocol. We established a procedure involving the sequential lysis of neutrophils in buffers of increasing tonicities that not only preserved and solubilized tyrosine phosphorylated proteins but also retained their enzymatic activities. The sequential lysis of neutrophils in hypotonic, isotonic and hypertonic buffers containing non-ionic detergents resulted in the solubilisation of a significant fraction of tyrosine phosphorylated proteins. Furthermore, we observed that in monosodium urate crystals-stimulated neutrophils, Lyn activity was enhanced in the soluble fraction recovered from the hypertonic fraction, but not from that of the first hypotonic lysis. The distribution of tyrosine phosphorylated proteins between the NP-40 soluble and insoluble fractions was both substrate- and agonist-dependent. In neutrophils stimulated with fMet-Leu-Phe, MSU crystals or by CD32 ligation, the tyrosine phosphorylated proteins were mostly insoluble. On the other hand, in GM-CSF-treated cells, the phosphoproteins were more equally distributed between the two fractions. The results of this study provide a new experimental procedure for the investigation of tyrosine phosphorylation pathways in activated human neutrophils which may also be applicable to other cell types.