Estrogen improves response accuracy and attenuates the disruptive effects of delta9-THC in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance

Despite evidence of an interaction between cannabinoids and estrogen in the brain, little information is available regarding the consequences of this interaction on behavior. A within-subjects design was used to examine the effects of estrogen and delta9-tetrahydrocannabinol (delta9-THC) on learning and memory in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance. Treatment with low physiological levels of estrogen, delivered in Silastic capsules, improved response accuracy without affecting response rate during acquisition. Estrogen also attenuated the ability of delta9-THC (0.56- 3.2 mg/kg) to decrease response accuracy and rate during acquisition and response accuracy during performance. Results indicate that estrogen can improve accuracy during acquisition of a nonspatial operant task and can attenuate delta9-THC- induced behavioral deficits.     

Impaired Microvascular Function in Normal Children: Effects of Adiposity and Poor Glucose Handling

Clustering of cardiovascular risk factors is thought to occur early in life. The endothelium is an important regulator of microvascular function. We investigated the relationship between microvascular function and cardiovascular risk factors in 145 normal, healthy children aged 11-14 years. Skin microvascular responses, measured using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), were negatively correlated with percentage body fat ( r =−0.20, P < 0.05 and r =−0.18, P < 0.05, respectively). Subjects were stratified into quintiles based on 2-h, post-feeding glucose levels. Subjects in the upper glucose quintile (range 7.4-11.4 mmol l⁻¹) showed significantly lower vasodilatation to both ACh (   P < 0.005  ) and SNP (   P < 0.02  ) than those in the lower quintile (range 3.9-4.9 mmol l⁻¹). Waist-to-hip ratio and the fasting insulin resistance index were significantly greater in subjects in the upper quintile than those in the lower quintile ( P < 0.001 and P < 0.05, respectively). Additionally, in subjects in the upper glucose quintile, fasting triglyceride correlated with fasting insulin ( r = 0.59, P < 0.001) and with the fasting insulin resistance index ( r = 0.49, P < 0.009), and plasma levels of cholesterol and 2-h glucose were also correlated ( r = 0.40, P < 0.05). In a cross-section of normal children, microvascular function was negatively associated with adiposity. Additionally, in a subgroup of subjects, there was a clustering of high post-feeding glucose, impaired microvascular function, increased insulin resistance and higher central fat distribution. These findings suggest that risk factors for adult cardiovascular disease begin to cluster in normal children, which might have important consequences for development of atherosclerosis later in life.     

Analysis of Scottish Duchenne and Becker muscular dystrophy families with dystrophin cDNA probes.

One hundred and thirty-two Scottish families, representing the majority of currently known cases in this country with at least one living subject affected by DMD (110) or BMD (22), were studied with a series of cDNA probes excluding the 3' region of the gene (probes 10-14). Using mainly HindIII digested DNA from affected males, 89 patients showed deletions which ranged from 1 to 32 HindIII fragments in size. Two patients were also detected with exon duplications. Abnormalities were found to be particularly concentrated in the area of probe cDNA 8, with 56 patients being deleted for at least one of the fragments detected by this probe. A second smaller concentration of deletions was found with probe 1-2a which showed 16 deletions and two duplications. The endpoints of cDNA deletions or duplications were determined with a maximum variability of one HindIII fragment in 83 patients, while the remaining eight patients had a single deletion endpoint defined. The deletions found in two of our patients appear to conflict with the previously stated exon order at the 5' end of the gene. Although no specific deletion patterns were apparent for DMD, the deletions found in 13 of the BMD patients all included the most proximal (10 kb) fragment detected by probe 8.     

Effects of signaled and unsignaled stressor on ECG T-wave amplitude

Thirty-six human subjects were exposed to noise (noxious US) under one of the following signal (CS) conditions: signaled stressor (SS), unsignaled stressor (NS) and a truly random control group (RS). Changes in ECG T-wave amplitude were used to index the stress response and the greatest change in amplitude occurred in the SS group. T-wave amplitude change was compared to HR change as an index of sympathetic stimulation and the former proved the more sensitive. The increased sympathetic responding in the SS condition suggests that a reliable signal may serve a physiologically adaptive purpose.     

Eosinophil granule lysis in vitro induced by soluble antigen antibody complexes

A simple test system is described, for the demonstration of antigen—antibody reactions capable of causing eosinophil granule lysis in vitro. The antigen preparations used were extracts of the nematode Amplicaecum robertsi and body fluid of Ascaris suum. Antisera were obtained from rats infested with Amplicaecum. Eosinophils were obtained from the peritoneal cavity of normal rats. Centrifugation of the cells to form a cell button was an essential step in the procedure. Lysis of eosinophils occurred with antiserum obtained from the animals between the 12th and 32nd days of infestation with Amplicaecum, and was accompanied by vacuole formation in macrophages and mast cell disruption. The reaction was most pronounced during the 3rd week. Serum from adrenalectomized infested animals caused the most marked changes in eosinophils. Serum from cortisonetreated infested animals failed to cause eosinophil changes.

Attempts at purification of the antigen in Ascaris body fluid resulted in two fractions with marked activity in the test system. The same two fractions were found to form precipitin lines on agarose gel diffusion against rat antiserum.

It is postulated that antigen—antibody complexes soluble in low concentration were responsible for the changes observed in the eosinophils, macrophages and mast cells. One or more labile factors in the serum were found to be necessary for eosinophil granule lysis. The evidence, though incomplete, would favour the suggestion that both labile antibody and complement were necessary.

     

In vitro regulation of thyroglobulin (Tg) autoantibody production by Tg-specific T-cell lines and hybridomas.

To define the interactions between self thyroglobulin (Tg)-reactive T and B we co-cultured enriched B cells taken from rat or mouse Tg-primed mice with major histocompatibility complex (MHC) class II-restricted T-cell lines specific for iodinated determinants on self-Tg, or hybridomas derived from those lines. Using two clonally distinct T-cell hybridomas, ADA2 and CH9, in vitro help for Tg autoantibody responses was observed using mouse (M)Tg-primed B cells and a 100 ng/ml MTg challenge. Using rat Tg-primed B cells and the same conditions, only CH9 provided help, indicating that the fine specificity of B cells influences their ability to interact with specific anti-Tg T-cell clones. In contrast to T-cell hybridomas, their parent T-cell lines MTg9B3 and MTg12B suppressed Tg autoantibody responses in vitro, although they augmented bystander proliferation of unprimed B cells. The MTg12B cells also (i) diminished the survival of Tg-primed B cells, and (ii) inhibited the proliferation of an antigen-presenting B-cell hybridoma (LK35.2) in a cytostasis assay. These findings together support the view that their suppressive activity is mediated through cytotoxicity. While the role of class II-restricted cytotoxic cells in thyroid autoimmunity is unknown, the results suggest that such cells may act to suppress autoantibody responses as well as to mediate tissue damage to class II-expressing thyroid cells.     

Light and Electron Microscopic Study of an Invasive Cribriform Carcinoma with Extensive Microcalcification Developing in a Breast with Silicone Augmentation

Although recent epidemiologic studies suggest that silicone augmentation of the breast is not associated with an increased risk of mammary carcinoma, cases of breast carcinoma arising in augmented breasts are being increasingly encountered as a large number of patients who had augmentation are getting older. A case of a 51-year-old woman with a 20-year history of breast augmentation who developed an invasive cribriform carcinoma associated with extensive microcalcification is presented. The patient had submammary silicone implants 20 years ago that were replaced, because of local complications, in subpectoral positions 10 years later. Dispersive X-ray microanalysis failed to demonstrate silicone in sections of the tumor and adjacent breast tissue. Appropriately fixed tumor tissue was available for electron microscopic examination. The tumor cells were rich in mitochondria, and their luminal surfaces were endowed with abundant microvilli, but the cell surfaces that came closest to the calcified microspheriols were devoid of microvilli and had cellular buddings between the microspheriols. It is suggested that the tumor cells might have been actively involved in the process of microcalcification.     

Bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans organizing pneumonia (BOOP), and other late-onset noninfectious pulmonary complications following allogeneic hematopoietic stem cell transplantation.

Pulmonary dysfunction is a significant complication following allogeneic hematopoietic stem cell transplantation (HSCT), and is associated with significant morbidity and mortality. Effective antimicrobial prophylaxis and treatment strategies have increased the incidence of noninfectious lung injury, which can occur in the early posttransplant period or in the months and years that follow. Late-onset noninfectious pulmonary complications are frequently encountered, but diagnostic criteria and terminology for these disorders can be confusing and therapeutic approaches are suboptimal. As a consequence, inaccurate diagnosis of these conditions may hamper the appropriate data collection, enrollment into clinical trials, and appropriate patient care. The purpose of this review is to clarify the pathogenesis and diagnostic criteria of representative conditions, such as bronchiolitis obliterans syndrome and bronchiolitis obliterans organizing pneumonia, and to discuss the appropriate diagnostic strategies and treatment options.