Regulation of in vitro cytotoxic T lymphocyte generation. II. Demonstration of noncytotoxic alloantigen-specific suppressor T lymphocytes

Both allospecific suppressor T lymphocytes (TsS) and nonspecific suppressor T lymphocytes (TsN) are activated in alloantigen-stimulated mixed leukocyte cultures (MLC). TsS and TsN can suppress cytotoxic T lymphocyte (CTL) induction upon transfer to fresh (second) MLC stimulated by the same alloantigens as in the first MLC (TsS or TsN) or by third-party alloantigens (TsN only). Evidence that TsS and TsN functions are performed by different T cell sets has been restricted to radioresistance of the former but not the latter. Separation of TsS from CTL has proven even more difficult. Methods are reported here which have allowed in vitro induction and functional separation of TsS from CTL and TsN in a totally allogeneic system. TsS are resistant to combined exposure to pyrilamine, a histamine1 antagonist and local anesthetic, during suppressor cell induction, and to X or gamma irradiation thereafter, while CTL precursors (CTL-P) and TsN are more sensitive to such treatments. This allowed us to use these treatments to generate TsS that are not contaminated with functional CTL, CTL-P or TsN. These data show that TsS regulate CTL induction by interacting with responding cell populations, rather than by cytotoxic depletion of stimulator cells.     

Results of a study to correlate serum prostate specific antigen and reproductive hormone levels in patients with localized prostate cancer.

This cross-sectional study was undertaken to determine whether serum hormones (free testosterone, androstenedione, luteinizing hormone, or prolactin) have any influence on serum prostate specific antigen (PSA) levels in patients with stage A-C prostate cancer. Blood samples were collected prior to any treatment in 36 patients; in 19 (group 1), three blood samples were collected 10 minutes apart between 9:00 AM and 9:30 AM for each patient and pooled together to avoid diurnal and episodic variation in serum testosterone values. In the remaining patients, only one sample could be collected (group 2). Free testosterone, androstenedione, luteinizing hormone, prolactin, and PSA levels were determined with appropriate radioimmunoassay techniques. Statistical analyses were performed separately for groups 1 and 2, and then with pooled data. None of the hormones in any of the analyses showed any association to serum PSA values except for prolactin for the pooled data and for group 2. This statistical significance for prolactin disappeared on multivariate analysis. There were 21 African-American men and 15 whites in the study; no racial differences in hormonal levels were found except for lower luteinizing hormone levels in African Americans in group 2 and pooled data. No differences were found between group 1 and group 2 in the mean serum prolactin and luteinizing hormone values. Serum free testosterone, androstenedione, and luteinizing hormone appeared to have no influence on serum PSA values in nonmetastatic cancer patients. Serum prolactin values were inversely associated with PSA values in univariate analysis for the pooled data; this disappeared in multivariate analysis. Unlike other studies that found higher serum testosterone levels in African-American college students than whites, no such differences were seen in this age group. Luteinizing hormone was lower in African-American men than in whites in the pooled study population. Further studies are needed to clarify our findings.     

Molecular typing of clinical and environmental isolates of Scedosporium prolificans by inter-simple-sequence-repeat polymerase chain reaction.

Invasive infections by Scedosporium prolificans have increased alarmingly in recent years, mainly in immunosuppressed patients. The epidemiology, pathogenesis and the natural habitat of this pathogen are practically unknown. Isolates of S. prolificans were distinguished from one another by inter-simple-sequence-repeat (ISSR) fingerprinting, a technique based on the high degree of polymorphism of the multisatellite genetic markers used. This technique was found useful for typing 84 isolates of S. prolificans from different countries and sources. The assemblage of S. prolificans isolates tested was extremely diverse, with 35 genotypes present. Several patients were found to have been infected or colonized by more than one strain. Overall, this technique facilitates the epidemiological study of S. prolificans infection.     

Optimization of peptide linker length in production of MHC class II/peptide tetrameric complexes increases yield and stability,and allows identification of antigen-specific CD4+T cells in peripheral blood mononuclear cells

Reliable, efficient systems for producing soluble HLA-DR molecules, suitable for multimerization and use as staining reagents, have proved elusive. We found that the addition of a flexible linker between peptide and N terminus of the DRB1*0101-chain (Crawford, F., Kozono, H., White, J., Marrack, P. and Kappler, J., Immunity 1998. 8: 675-682.), results in greater in vitro folding efficiency of Escherichia coli-expressed alpha- and beta-chains, and increases both the yield and stability of the DRA1*0101/DRB1*0101/peptide complexes. Although a 10-amino acid linker functioned efficiently for a 20mer epitope from HIV p24, a longer linker was required to produce a DR1 MHC class II tetramer with the influenza hemagglutinin epitope (HA(306-318)). The DR1-HA tetramer was able to stain positively over 98% of a specific clone (HA 1.7) with only a brief 30-min incubation. The tetrameric complexes detected clone cells diluted into PBMC, with high sensitivity, coupled with low background staining in CD4(+) cells. It was possible to detect antigen-specific CD4(+) T cells within a population of PBMC stimulated with the HA peptide. This demonstrates the potential to monitor CD4(+) T cell responses in peripheral blood in a number of clinical scenarios.     

Effects of interparental violence on the psychological adjustment and competencies of young children

Preschool children (N = 107) were divided into 4 groups on the basis of maternal report; home and shelter groups exposed to verbal and physical conflict, a home group exposed to verbal conflict only, and a home control group. Parental ratings of behavior problems and competencies and children's self-report data were collected. Results show that verbal conflict only was associated with a moderate level of conduct problems: verbal plus physical conflict was associated with clinical levels of conduct problems and moderate levels of emotional problems; and verbal plus physical conflict plus shelter residence was associated with clinical levels of conduct problems, higher level of emotional problems, and lower levels of social functioning and perceived maternal acceptance. Findings suggests a direct relationship between the nature of the conflict and residence and type and extent of adjustment problems.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Use of past care markers in risk-adjustment: accounting for systematic differences across providers

The European Journal of Health Economics - Risk-adjustment models are used to predict the cost of care for patients based on their observable characteristics, and to derive efficient and equitable...     

Prior Pelvic Osteotomy Affects the Outcome of Subsequent Total Hip Arthroplasty

BackgroundAlthough pelvic osteotomy (PO) is an important surgical procedure that can alleviate symptoms and potentially slow progression of osteoarthritis in patients with development dysplasia of the hip, some patients eventually require conversion to total hip arthroplasty (THA). This study aimed to determine the outcome of conversion THA in patients with prior PO.MethodsForty nine patients with a history of prior PO who underwent conversion THA at a single institution were matched at a 1:3 ratio based on the date of surgery, age, gender, and body mass index with 147 developmental dysplasia of the hip patients who underwent primary THA without prior PO. A retrospective chart review was performed to compare outcomes at a minimum follow-up of 2 years.ResultsPatients with prior PO required more supplemental screw fixation for the acetabular component (59.2% vs 38.1%, P = .016), more autologous bone grafting (24.5% vs 11.6%, P = .048), had a longer mean operative time (106.0 vs 79.8 minutes, P < .001), and greater estimated blood loss (350.0 vs 206.8 mL, P = .015). Patients with prior PO had smaller cup version angle (26.0° vs 29.0°, P = .012) and greater discrepancy in the limb length (10.3 vs 7.26 mm, P = .041). Eight hips (16.3%) with prior PO and 6 (4.1%) without osteotomy required reoperation (P = .008). There was no difference in outcome scores at the latest follow-up.Conclusion: THA after prior PO is technically demanding, leading to longer operative times, greater blood loss, and variation in implant placement. Although functional outcomes are similar, THA after a prior PO is more likely to require reoperation.ConclusionTHA after prior PO is technically demanding, leading to longer operative times, greater blood loss, and variation in implant placement. Although functional outcomes are similar, THA after a prior PO is more likely to require reoperation.     

Is patient age associated with risk of malignancy in a ≥4 cm cytologically benign thyroid nodule?

BackgroundCurrent data regarding the risk of malignancy in a large thyroid nodule with benign fine-needle aspiration biopsy(FNAB) is conflicting. We investigated the impact of patient age on the risk of malignancy in nodules≥4 cm with benign cytology.MethodsWe performed a single-institution retrospective review of patients who underwent surgery from 07/2008–08/2019 for a cytologically benign thyroid nodule ≥4 cm. The relationship between malignant histopathology and patient and ultrasound features was assessed with multivariable logistic regression.ResultsOf 474 nodules identified, 25(5.3%) were malignant on final pathology. In patients <55 years old, 21/273(7.7%) nodules were malignant, compared to 4/201(2.0%) in patients ≥55. Patient age ≥55 was independently associated with significantly lower risk of malignancy(OR:0.2,95%CI:0.1–0.7,p = 0.011). Increasing nodule size >4 cm and high-risk ultrasound features were not associated with risk of malignancy(OR:1.0,95%CI:0.7–1.4,p = 0.980, and OR:9.6,95%CI:0.9–107.8,p = 0.066, respectively).ConclusionsPatients <55 years old are 3.7-fold more likely to have a falsely benign FNA biopsy in a nodule≥4 cm.