Tolerance induction by "megadose" hematopoietic transplants: donor-type human CD34 stem cells induce potent specific reduction of host anti-donor cytotoxic T lymphocyte precursors in mixed lymphocyte culture

BACKGROUND: Recently, the use of megadoses of CD34+ hematopoietic progenitors has been reported to abrogate resistance to engraftment, thus overcoming major histocompatibility barriers in bone marrow transplantation in leukemia patients. METHODS: The ability of human CD34+ cells to possess potent tolerizing activity was studied by limiting dilution analysis of cytotoxic T lymphocyte (CTL) precursors (CTL-p) in human peripheral blood lymphocytes after addition of purified CD34+ cells. RESULTS: The addition of purified human CD34+ cells to primary mixed lymphocyte culture led to a marked reduction of antiallogeneic CTL-p frequency against stimulator cells of the same origin, compared with the response against cells of third-party origin. The CD34+ cells caused a marked inhibition of the CTL activity, when added at an equal number with the responder T cells, and they were still present after the mixed lymphocyte culture, which suggests that no significant killing of CD34+ cells had occurred. The tolerizing activity is abrogated by irradiation and requires cell contact. This pattern of tolerization most closely resembles what has been ascribed to veto cells in other systems. Phenotypic analysis of the purified CD34+ cells showed that they express MHC class I and class II antigens, but do not express costimulatory molecules of the B7 family. CONCLUSIONS: It is possible, that CD34+ cells in the megadose transplants-perhaps by their inability to provide costimulatory molecules-are actively reducing the frequency of CTL-p directed against their antigens, and thereby help to overcome allogeneic rejection, and enhance their own engraftment.     

In vivo induction of specific cytotoxic T lymphocytes in mice and rhesus macaques immunized with DNA vector encoding an HIV epitope fused with hepatitis B surface antigen

BACKGROUND: In human blood basophils, cross-linking the high-affinity IgE receptor Fc epsilonRI with multivalent antigen activates a signaling pathway leading to Ca2+ mobilization, actin polymerization, shape changes, secretion, and cytokine production. METHODS AND RESULTS: The role of tyrosine kinases in human Fc epsilonRI signaling was explored by using human basophils isolated by Percoll gradient centrifugation followed by negative and/or positive selection with antibody-coated magnetic beads. Fc epsilonRI cross-linking of more than 95% pure basophil preparations activates the protein-tyrosine kinases Lyn and Syk, previously linked to Fc epsilonRI-coupled rodent mast cell activation, as well as Zap-70, previously implicated in T-cell receptor signaling, and causes the tyrosine phosphorylation of multiple proteins. The presence of Lyn, Syk, and Zap-70 in basophils was confirmed by Western blotting in lysates of highly purified basophils and independently by confocal fluorescence microscopy in cells labeled simultaneously with kinase-specific antibodies and with the basophil-specific antibody 2D7. Comparable amounts of Lyn and Syk were found in basophils and B cells, whereas T cells appear to have greater amounts of Zap-70 than basophils. The tyrosine kinase inhibitor piceatannol spares IgE-mediated Lyn activation but inhibits IgE-induced Syk and Zap-70 activation as well as overall protein tyrosine phosphorylation and secretion. Overall protein-tyrosine phosphorylation increases steadily over a range of anti-IgE concentrations that are low to optimal for secretion. However, tyrosine phosphorylation continues to increase at high anti-IgE concentrations that elicit very little secretion (the characteristic high-dose inhibition of secretion). CONCLUSIONS: Our data demonstrate the association of anti-IgE-stimulated, protein-tyrosine phosphorylation by a cascade of tyrosine kinases, including Zap-70 as well as Lyn and Syk, with the initiation of Fc epsilonRI-mediated signaling in human basophils.     

Compliance with gloving in anesthesia: an observational study of gloving practice at induction of general anesthesia

STUDY OBJECTIVE: To gather direct observational data on anesthesiologists' compliance with universal precautions' gloving standards during induction of general anesthesia. DESIGN: Prospective, observational study. SETTING: Operating theaters of an Israeli government teaching hospital. SUBJECTS: Over a four-month period, all "first case of the day" general anesthetics were observed to determine if the anesthesiologist directly administering patient care wore gloves during the period of anesthetic induction. All anesthesia department members were observed and none was aware of the ongoing study. MEASUREMENTS AND MAIN RESULTS: Resident anesthesiologists were found to be more compliant with gloving policy than their attendings (61.8% vs. 33.7%, p < 0.0001). However, the lower compliance among the attendings was entirely attributable to the most senior staff members (over age 55 years) whose compliance rate was 11.5% versus 55.6% for attending staff below age 55 years (p < 0.0001). Departmental compliance as a whole was 49.6%. Compliance in pediatric cases averaged 10% and was equally poor among all department staff. CONCLUSIONS: Although glove use remains inconsistent, in less than one and one half years since institution of a departmental gloving policy, a substantial degree of compliance was achieved. Nevertheless, further efforts are still needed to improve compliance with universal precautions. In this study, glove use was particularly deficient in pediatric cases and among senior staff aged 55 years and older. Pinpointing specific areas of greatest deficiency may prove useful in guiding additional efforts to improve compliance with universal precautions.     

Placement of a coated stent in esophagotracheal fistula: initial experience with an "aortic stent"

Clinical and biological pitfalls that lead to incorrect or delayed diagnoses of airport malaria are described based on 7 cases reported from the Paris region in the summer of 1994. We also report the outcome and the epidemiological features of these patients.     

Pulmonary cavitation lesions in patients infected with the human immunodeficiency virus: an analysis of a series of 78 cases

BACKGROUND: To assess the clinical, radiologic and microbiological features of lung cavitation and HIV infection. Evaluation of the differences related to this disease in the last years. PATIENTS AND METHODS: Retrospective review of all patients with lung cavitation and HIV infection admitted at our hospital from January 1989 until December 1994 and prospective study of all patients with the same characteristics during 1995 and 1996. Lung cavitation was defined as any parenchymal lesion, with air content, visible in a simple X-ray and greater than 1 cm of diameter. Criteria for confirmed, probable or possible diagnosis were defined. RESULTS: 78 cases of lung cavitation have been identified in 73 patients. The radiologic patterns included unilobar and multilobular involvement in 31 and 47 cases, respectively. Cavities were multiple and single in 40 and 38 cases respectively. Findings with fine needle aspiration biopsy (FNAB) were diagnostic in 11 out of 14 cases. A clinical diagnosis was performed in all 78 cases, with microbiological results in 69 cases (88.5%): Mycobacterium tuberculosis in 20, Pneumocystis carinii in nine, Pseudomonas aeruginosa in nine, Staphylococcus aureus in eight (5 endocarditis with cavitary septic emboli), Rhodococcus equi in six, P. aeruginosa and S. aureus in three, Salmonella enteritidis in three, Cryptococcus neoformans in two, Aspergillus fumigatus in two and others in 7 cases. Confirmed, probable and possible diagnosis was considered in 54, 15 and 9 cases, respectively. Thirteen episodes of spontaneous pneumothorax were found. CONCLUSIONS: The lung cavitation rate is low, compared with the number of admissions related to HIV infection; nevertheless, many of them are in close relationship with HIV infection, and most of them are caused by treatable infections. It is important to know the clinical and radiological characteristics, in order to establish an early diagnosis and an appropriate therapy. Pseudomonas aeruginosa is becoming an important cause of lung cavitation. In our series, spontaneous pneumo-thorax was not related to Pneumocystis carinii pneumonia in 61.5% of cases.     

"I'd rather not talk about it": Emotion parenting in families of children with an anxiety disorder.

This study examined emotion socialization practices in families of children with an anxiety disorder (AD; n = 28) and of children who had no diagnoses (ND; n = 28) and considered gender differences. Youth (aged 8-13) and both parents discussed times when the child felt anxious, angry, and happy, for 5 min each. Fathers of AD children engaged in less explanatory discussion of emotion overall and exhibited less positive affect and more negative affect when interacting with sons than did fathers of ND children. Similar patterns emerged for mothers, although specific results varied by emotion type and child gender. Children with an AD demonstrated less positive affect overall and engaged in fewer problem-solving emotion regulation strategies when discussing anxious and angry situations than did children in the ND group. In both AD and ND groups, fathers appeared to have greater involvement in emotion-related discussions with sons versus daughters. The results highlight parents' contributions to the emotional development of their children, the ways in which socialization may go awry in families of AD children, and the implications for children's emotional functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Testicular "tumor" of the adrenogenital syndrome: a case report of an unusual association with myelolipoma and seminoma in cryptorchidism

BACKGROUND: Males with congenital adrenal hyperplasia may develop bilateral testicular masses in early adult life. These are not malignant and generally regress with corticosteroid therapy. The authors report a case occurring in a 44-year-old man with associated seminoma and myelolipoma in an undescended testis. METHODS: The testicular tumors were analyzed by histologic, flow cytometric, and ultrastructural techniques. RESULTS: The tumors in both testes were comprised of polygonal cells with abundant granular eosinophilic cytoplasm, occasionally with brown (lipochrome) pigment and round nuclei of various sizes with prominent nucleoli. These cells were grouped into nodules by dense and sometimes thick fibrous trabeculae in the right testis. The areas corresponding to the fibrous trabeculae in the left (intraabdominal) testis were replaced by mixture of hematopoietic (myeloid) and fatty tissue in various proportions characteristic of myelolipoma. The left testis also had a well demarcated tumor that was diagnostic of seminoma. Electron microscopy demonstrated abundant smooth endoplasmic reticulum, a moderate number of mitochondria with tubulovesicular cristae, lipid droplets, and lipofuscin granules in the polygonal cells. No Reinke's crystals were observed. The patient received corticosteroids for his adrenocorticoid deficiency and also underwent external beam irradiation to the retroperitoneum for seminoma. CONCLUSIONS: This case illustrates an unusual presentation of a testicular tumor in a patient with the adrenogenital syndrome as well as with myelolipoma and seminoma in a cryptorchid testis. The possibility of an associated neoplasm that could be potentially fatal should be considered whenever a testicular tumor of the adrenogenital syndrome continues to grow despite adequate hormonal treatment.     

Neuronal sprouting in mouse sensory ganglia infected with herpes simplex virus type 2 (HSV-2): induction of growth-associated protein (GAP-43) and ultrastructural evidence

Herpes simplex virus (HSV) is neurotropic and when inoculated on the mouse footpad is retrogradely transported to the associated dorsal root ganglia (DRG), where infection is established. Previous observations suggest that, after HSV infection, sensory ganglion neurons may mount a sprouting response. In our HSV-infected DRG model, we investigate this issue by (1) examining expression of growth-associated protein (GAP-43), a molecule known to be induced by growing axons, and (2) determining ultrastructurally whether HSV-infected dorsal roots contain neurites. In a time course study, we show that GAP-43 is induced both in HSV-infected DRG and their central processes. The increase in GAP-43 is first seen 2 weeks following unilateral footpad inoculation in both cell bodies and dorsal roots, and is sustained at 1 month post inoculation in roots but not in perikarya. Large bundles of unmyelinated small caliber axons, lacking Schwann cell ensheathment, are observed by electron microscopy in dorsal roots 2 weeks and 1 month following inoculation. These profiles resemble developing or regenerating neurites and are rarely seen in roots of mock-infected or uninfected controls. The increased GAP-43 immunoreactivity and ultrastructural changes shown here, in conjunction with previously documented selective neuropeptide and enzyme alterations, confirm that a sprouting response is mounted in sensory ganglia following acute HSV infection.     

Single-breath inhalation induction of sevoflurane anaesthesia with and without nitrous oxide: a feasibility study in adults and comparison with an intravenous bolus of propofol

The induction characteristics of sevoflurane in nitrous oxide and oxygen were compared with sevoflurane in oxygen alone and a propofol infusion. A vital capacity technique was used for the gaseous induction groups using a Mapleson A system and a 4-litre reservoir bag. Four end-points of anaesthesia were recorded: time to cessation of finger tapping, time to loss of eyelash reflex, time to jaw relaxation and time to regular settled breathing after laryngeal mask airway insertion. We also recorded sequential blood pressure and pulse rate, the incidence of adverse airway events and the acceptability of the induction technique. Propofol had a faster time to cessation of finger tapping (p < 0.05) and jaw relaxation (p < 0.01). These differences disappeared with the final induction stage and sevoflurane in nitrous oxide and oxygen had the faster time to regular settled breathing, though this did not reach statistical significance. Cardiovascular stability was good and comparable in all groups. There were few adverse airway events in any group and none caused oxygen saturation to fall below 96%. There was more excitation in the gaseous induction groups, though this did not interfere with induction. Patient satisfaction with induction was high.     

The "common cause hypothesis" of cognitive aging: Evidence for not only a common factor but also specific associations of age with vision and grip strength in a cross-sectional analysis.

A prominent hypothesis in cognitive aging is the existence of a common factor that is responsible for age-related deterioration in cognitive and noncognitive processes. A multiple indicators, multiple causes model was used to examine the nature of this common factor and its relationship to age, gender, and the apolipoprotien E (APOE) genotype. The common factor was modeled by using 10 indicator variables with 374 participants aged between 77.4 and 98.7 years. A latent factor was identified, with all indicators except blood pressure loading significantly. This factor could be established in 2 age strata within the sample. After controlling for the effects of gender, APOE, and level of education, direct effects of age were seen on visual functioning and grip strength. APOE was significantly associated with memory but not with the common factor. The findings suggest that a number of specific processes may operate concurrently with the common cause factor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Young inflorescence-bearing shoots with roots of Tradescantia clone BNL 4430 cultivated in nutrient solution circulating systems: an alternative to potted plants and cuttings for mutagenicity tests

The use of young inflorescence-bearing shoots with roots of Tradescantia clone BNL 4430 cultivated in a nutrient solution circulating (NSC) growth chamber was tested and developed as an alternative method for using Tradescantia plants in mutagenicity testings. The NSC growth chamber was designed for our requirements, based on trial cultivations of the shoots with roots in its smaller-sized prototype. The nutrient solution used was a 1/2500 Hyponex solution. The characteristics of this clone, i.e., many new shoots constantly emerging from the basal nodes one after another and its short height favorable for early flowering, made it possible to prepare many young inflorescence-bearing shoots with roots at one time. A simplified NSC cultivation system could also be developed at a lower cost, and by using it together with the NSC growth chamber, recycling of untreated materials was established for supplying steadily enough amounts of young inflorescence-bearing shoots with roots for mutagenicity testings. Compared with traditional methods of using potted plants or cuttings, the new method exhibited more stable flower production, better stamen-hair growth and a significantly lower spontaneous (background) mutation frequency, and could produce more inflorescences per space. The use of such young inflorescence-bearing shoots with roots was therefore judged to be satisfactory to serve as a new mutagenicity test system alternating with potted plants and cuttings.     

Cervical ripening before induction of labour in patients with an unfavourable cervix: a comparative randomized study of the Atad Ripener Device, prostaglandin E2 vaginal pessary, and prostaglandin E2 intracervical gel

OBJECTIVE: To evaluate relations between hoof and performance data from bulls fed in a 112-day standardized postweaning feedlot performance test. ANIMALS AND DESIGN: Breeds included were Angus (n = 20), Brangus (n = 19), Hereford (n = 31), and Simmental (n = 53). Hoof measurements, scores, and a 0.5-g hoof tissue sample were obtained from the right forefoot of bulls on days 1 and 112 of 4 tests conducted in 3 locations in Arkansas. Data were analyzed, using least squares ANOVA. The model used included an overall mean, breed, farm of origin within breed, initial age, and initial weight within breed and residual. Residual and canonical correlations of the traits studied were calculated. RESULTS: Residual correlations were found between some hoof minerals. Canonical correlations between performance traits and hoof minerals, between hoof characteristics and hoof minerals, and between hoof characteristics and performance traits were 0.62 and 0.45 (P < 0.005), 0.54 and 0.40 (P < 0.05), and 0.56 (P < 0.01) and 0.26 (P > 0.05), respectively. CONCLUSIONS: These data suggest that a relation exists between performance traits and hoof mineral composition and hoof characteristics and mineral composition. The visual scoring system for these data did not genetically separate bulls on the basis of claw quality. CLINICAL IMPLICATIONS: By selecting bulls with high claw quality, cattle producers are decreasing the chances of premature culling because of hoof laminitis. Therefore, by obtaining hoof measurements and mineral composition in a feedlot performance test, producers should have the tools to select bulls for increased lifetime performance.     

Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins

There is an increasing interest in identifying potent cancer preventive and therapeutic agents against breast cancer. Silymarin, a flavonoid antioxidant isolated from milk thistle, exerts exceptionally high to complete anticarcinogenic effects in tumorigenesis models of epithelial origin. In this study, we investigated the anticarcinogenic effect of silymarin and associated molecular mechanisms, using human breast carcinoma cells MDA-MB 468. Silymarin treatment resulted in a significantly high to complete inhibition of both anchorage-dependent and anchorage-independent cell growth in a dose- and time-dependent manner. The inhibitory effects of silymarin on cell growth and proliferation were associated with a G1 arrest in cell cycle progression concomitant with an induction of up to 19-fold in the protein expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21. Following silymarin treatment of cells, an incremental binding of Cip1/p21 with CDK2 and CDK6 paralleled a significant decrease in CDK2-, CDK6-, cyclin D1-, and cyclin E-associated kinase activity with no change in CDK2 and CDK6 expression but a decrease in G1 cyclins D1 and E. Taken together, these results suggest that silymarin may exert a strong anticarcinogenic effect against breast cancer and that this effect possibly involves an induction of Cip1/p21 by silymarin, which inhibits the threshold kinase activities of CDKs and associated cyclins, leading to a G1 arrest in cell cycle progression.