Modulation of disease severity of dystrophic epidermolysis bullosa by a splice site mutation in combination with a missense mutation in the COL7A1 gene

Dystrophic epidermolysis bullosa (EBD) is a clinically heterogeneous skin disorder, characterized by abnormal anchoring fibrils (AF) and loss of dermal-epidermal adherence. EBD has been linked to the COL7A1 gene at chromosome 3p21 which encodes collagen VII, the major component of the AF. Here we investigated two unrelated EBD families with different clinical phenotypes and novel combinations of recessive and dominant COL7A1 mutations. Both families shared the same recessive heterozygous 14 bp deletion at the exon-intron 115 boundary of the COL7A1 gene. The deletion caused in-frame skipping of exon 115 and the elimination of 29 amino acid residues from the pro-alpha1(VII) polypeptide chain. As a result, procollagen VII was not converted to collagen VII and the C-terminal NC-2 propeptide which is normally removed from the procollagen VII prior to formation of the anchoring fibrils was retained in the skin. All affected individuals also carried missense mutations in exon 73 of COL7A1 which lead to different glycine- to-arginine substitutions in the triple-helical domain of collagen VII. Combination of the deletion mutation with a G2009R substitution resulted in a mild phenotype. In contrast, combination of the deletion with a G2043R substitution led to a severe phenotype. The G2043R substitution was a de novo mutation which alone caused a mild phenotype. Thus, different combinations of dominant and recessive COL7A1 mutations can modulate disease activity of EBD and alter the clinical presentation of the patients.      

Total ovarian volume before human chorionic gonadotrophin administration for ovulation induction may predict the hyperstimulation syndrome

Total ovarian volumes were measured before the administrationof HCG in 42 women undergoing treatment for infertility by in-vitrofertilization (IVF) and embryo transfer and considered to havean exaggerated response to stimulation (>20 follicles). Sevenwomen who subsequently developed moderate or severe ovarianhyperstimulation syndrome (OHSS) (n = 7; group 1) were comparedwith 35 matched controls (five matched controls per case; n= 35; group 2) of similar age, number of follicles and durationof infertility who underwent follicular stimulation, oocyterecovery, in-vitro fertilization and embryo transfer duringthe same period but did not develop moderate or severe OHSS.The mean age, duration of infertility and total number of follicleswere similar but the mean total ovarian volume was significantlyhigher in the group of women who developed moderate or severeOHSS compared with controls (271.00 ± 87.00 versus 157.30± 54.20 ml; P < 0.01). We conclude that total ovarianvolume measured before HCG administration is higher in womenwho develop moderate or severe OHSS compared with controls andmay therefore be used as an additional parameter in the preventativestrategy for the ovarian hyperstimulation syndrome.     

L-selectin expression differentiates T cells isolated from different lymphoid tissues in cattle but does not correlate with memory.

L-selectin (LECAM-1, LAM-1) was expressed by a high proportion of CD4+ and CD8+ T cells, as well as almost all of the gamma delta T-cell receptor (TcR)+ (WC1+) T cells, isolated from blood, lymph nodes or tonsils. CD4+ T cells in the lamina propria of the gut villi and CD8+ T cells in the villous epithelium as well as the majority of WC1+ T cells in the gut mucosa were L-selectin-. The proportion of T cells from Peyer's patches that synthesized the molecule was intermediate between the value for blood and gut mucosa. Expression of L-selectin therefore marks T cells in cattle with a distinct tissue distribution that correlates with its function as the peripheral node homing receptor. The proportion of CD4+ and CD8+ T cells in the circulation that were L-selectin+ decreased with age. Unlike CD45R, expression of L-selectin was not related to CD4 T-cell memory as judged by proliferation in transformation assays to soluble antigen. Three-colour immunofluorescent staining demonstrated four subpopulations of CD4 and CD8 T lymphocytes in peripheral blood mononuclear cells (PBMC) that were CD45R+, L-selectin+; CD45R+, L-selectin-; CD45R-, L-selectin+; CD45R-, L-selectin-. CD4(4) memory cells were CD45R- and L-selectin+ or L-selectin-. Taken with earlier studies the reported observations demonstrated that only one of the four phenotypes of the CD4+ T cells in blood is present in the lamina propria of the gut villi and these are CD45R-, L-selectin-. Two of the four phenotypes of CD8+ T cells were present in the gut epithelium; these were CD45R+, L-selectin- or CD45R-, L-selectin-. Expression of the bovine molecule was not rapidly down-regulated on T cells following activation by exposure to phorbol myristate acetate.     

Pathogenicity of PMV-3/Turkey/England/Midland poultry holdings/1981 for chickens and turkeys

The original 1981 English isolate of avian paramyxovirus type 3 from turkeys was of higher pathogenicity to chickens than the prototype 1968 isolate turkey/Wisconsin. It was lethal to chicks aged one day when given by intravenous or intracerebral inoculation. The age susceptibility was increased to one week by use of an inbred strain or betamethasone. The virus was more pathogenic to its natural host as outbred turkeys aged one week died after intravenous inoculation of the virus and contact transmission resulted in stunting and seroconversion of 2-week-old birds. Monoclonal antibodies to both viral glycoproteins, but not to the two internal proteins, protected one-day-old turkeys from 1000 intravenous LD50 of virus when they were inoculated one day after virus. This was considered to be analogous to maternally derived immunity and emphasised the role of yolk sac antibody in the protection of young stock.     

Male mating speed as a component of fitness inDrosophila

From a survey of published data on the genusDrosophila, it is clear that male mating speed or male virility is probably the most important component of fitness. Rapid matings tend to be controlled by the male genotype, while the genotype of the female may assume importance for slower matings. Where data exist, male mating speed is subject to directional selection in the direction of rapid speed, as would be expected for an important component of fitness.Supported by the Australian Research Grants Committee.     

The New Normal? Patient Satisfaction and Usability of Telemedicine in Breast Cancer Care

Annals of Surgical Oncology - Telemedicine was adopted to minimize exposure risks for patients and staff during the coronavirus disease 2019 pandemic. This study measured patient satisfaction and...     

Kidney recipients with allograft failure,transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.     

Preoperative hemostatic assessment of the adenotonsillectomy patient

Intraoperative or postoperative hemorrhage in the patient who has undergone an adenotonsillectomy because of an unrecognized hemostatic defect may increase morbidity and can be potentially life-threatening to the patient in what should be a "routine" procedure. Preoperative identification of occult hemostatic abnormalities, coupled with perioperative management directed at correcting the effects of the defects, should serve to reduce the incidence of this distressful complication. Routine use of preoperative laboratory screening tests for this purpose has been discouraged recently as a result of concerns over cost-effectiveness and the low predictiveness of the tests for bleeding. Our experience with the routine use of a comprehensive hemostatic laboratory screening panel--which includes a bleeding time test--in the adenotonsillectomy patient population demonstrated that 11.5% of our patients had abnormal initial screening laboratory tests; these results were ultimately attributable to occult hemostatic defects. Clinical history, the universally recommended method of preoperative hemostatic assessment, failed to detect any previously unrecognized coagulation disorder. Laboratory screening improved preoperative detection of occult hemostatic defects and allowed for appropriate alterations in perioperative care. Our results with this approach are presented, along with illustrative case histories and a discussion of the current recommendations for preoperative laboratory screening of the hemostatic system, as found in a review of the literature.