Structure–function studies of blood and air capillaries in chicken lung using 3D electron microscopy

Avian pulmonary capillaries differ from those of mammals in three important ways. The blood–gas barrier is much thinner, it is more uniform in thickness, and the capillaries are far more rigid when their transmural pressure is altered. The thinness of the barrier is surprising because it predisposes the capillaries to stress failure. A possible mechanism for these differences is that avian pulmonary capillaries, unlike mammalian, are supported from the outside by air capillaries, but the details of the support are poorly understood. To clarify this we studied the blood and air capillaries in chicken lung using transmission electron microscopy (EM) and two relatively new techniques that allow 3D visualization: electron tomography and serial block-face scanning EM. These studies show that the pulmonary capillaries are flanked by epithelial bridges composed of two extremely thin epithelial cells with large surface areas. The junctions of the bridges with the capillary walls show thickening of the epithelial cells and an accumulation of extracellular matrix. Collapse of the pulmonary capillaries when the pressure outside them is increased is apparently prevented by the guy wire-like action of the epithelial bridges. The enlarged junctions between the bridges and the walls could provide a mechanism that limits the hoop stress in the capillary walls when the pressure inside them is increased. The support of the pulmonary capillaries may also be explained by an interdependence mechanism whereby the capillaries are linked to a rigid assemblage of air capillaries. These EM studies show the supporting structures in greater detail than has previously been possible, particularly in 3D, and they allow a more complete analysis of the mechanical forces affecting avian pulmonary capillaries.     

Adenovirus vaccine vectors expressing hepatitis B surface antigen: importance of regulatory elements in the adenovirus major late intron

Adenovirus types 4 and 7 are currently used as live oral vaccines for prevention of acute respiratory disease caused by these adenovirus serotypes. To investigate the concept of producing live recombinant vaccines using these serotypes, adenovirus types 4 (Ad4) and 7 (Ad7) were constructed that produce HBsAg upon infection of cell cultures. Ad4 recombinants were constructed that express HBsAg from a cassette inserted 135 bp from the right-hand terminus of the viral genome. The cassette contained the Ad4 major late promoter followed by leader 1 of the tripartite leader, the first intervening sequence between leaders 1 and 2, leaders 2 and 3, the HBsAg gene, and tandem polyadenylation signals from the Ad4 E3B and hexon genes. Using this same cassette, a series of Ad4 recombinants expressing HBsAg were constructed with deletions in the intervening sequence between leaders 1 and 2 to evaluate the contribution of the downstream control elements more precisely. Inclusion of regions located between +82 and +148 as well as +148 and +232 resulted in increases in expression levels of HBsAg in A549-infected cells by 22-fold and 44-fold, respectively, over the levels attained by an adenovirus recombinant retaining only sequences from +1 to +82, showing the importance of these elements in the activation of the major late promoter during the course of a natural Ad4 viral infection. Parallel increases were also observed in steady-state levels of cytoplasmic HBsAg-specific mRNA. When similar Ad7 recombinant viruses were constructed, these viruses also expressed 20-fold more HBsAg due to the presence of the intron. All Ad4 and Ad7 recombinants produced HBsAg particles containing gp27 and p24 which were secreted in the medium. When dogs were immunized intratracheally with one of these Ad7 recombinants, they seroconverted to both Ad7 and HBsAg to a high level.     

Evidence of progesterone receptors in the mucosa of the urinary bladder.

OBJECTIVE: To investigate whether progesterone receptors are present in the mucosa of the urinary bladder of continent premenopausal women compared with continent postmenopausal women. MATERIALS AND METHODS: Fifty-seven biopsies from the mucosa of the trigone and lateral wall of the urinary bladder were examined by the avidin-biotin-peroxidase immunohistochemical technique for the presence of estrogen and progesterone receptors. The specimens were obtained at cystoscopy performed to investigate hematuria in 42 patients and neoplasia in 15. The study group (n = 29) comprised non-pregnant premenopausal women in the luteal phase of their menstrual cycle and the control group (n = 28) comprised postmenopausal women. None of the subjects had urinary incontinence or was taking medication with hormones. In no case did the primary lesion involve the specimen used for laboratory analysis. RESULTS: There was positive immunostaining with estrogen in 28 patients of the study group (96.5%) and 4 (14.4%) in the control group (p<0.0001). The 28 samples of the study group also showed positive immunostaining for progesterone receptors. There was positive immunostaining with progesterone in 18 samples (64.3%) of the control group (p<0.01). Fourteen samples (50%) of the control group thus showed positive immunostaining for progesterone but no evidence of positive immunostaining with estrogen. Immunostaining for estrogen and progesterone receptors was similar in trigonal and lateral wall samples. CONCLUSION: In continent pre- and post-menopausal women, a direct progestogenic effect on the mucosa of the urinary bladder seems likely in addition to estrogen.     

Lithium potentiation of tricyclic antidepressants following lack of T3 potentiation

Four patients whose depressions were failing to respond to administration of tricyclic antidepressants were given separate trials of T3 and lithium. In all four cases, T3 failed to potentiate the antidepressant, whereas the lithium did.     

Is there paradoxical growth hormone response to thyrotropin-releasing hormone in depression?

Several investigators have reported a paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) in depressed patients, but other studies have failed to confirm this. In the present study, the GH response to TRH was studied in depressed patients and normal subjects. The rate of paradoxical GH response to TRH in depression was no different than that observed in control subjects. This was the case whether the data was examined using mean values or using frequency of abnormal responses. Patients with blunted thyrotropin (TSH) responses did not differ in GH release from patients with normal TSH response. A variety of factors may have contributed to the earlier reports of a positive GH response to TRH, including the definition of paradoxical GH release and the fact that depressed patients exhibit more frequent spontaneous diurnal GH release than do normal subjects.     

A multi-feature and multi-channel univariate selection process for seizure prediction.

OBJECTIVE: To develop a prospective method for optimizing seizure prediction, given an array of implanted electrodes and a set of candidate quantitative features computed at each contact location. METHODS: The method employs a genetic-based selection process, and then tunes a probabilistic neural network classifier to predict seizures within a 10 min prediction horizon. Initial seizure and interictal data were used for training, and the remaining IEEG data were used for testing. The method continues to train and learn over time. RESULTS: Validation of these results over two workshop patients demonstrated a sensitivity of 100%, and 1.1 false positives per hour for Patient E, using a 2.4s block predictor, and a failure of the method on Patient B. CONCLUSIONS: This study demonstrates a prospective, exploratory implementation of a seizure prediction method designed to adapt to individual patients with a wide variety of pre-ictal patterns, implanted electrodes and seizure types. Its current performance is limited likely by the small number of input channels and quantitative features employed in this study, and segmentation of the data set into training and testing sets rather than using all continuous data available. SIGNIFICANCE: This technique theoretically has the potential to address the challenge presented by the heterogeneity of EEG patterns seen in medication-resistant epilepsy. A more comprehensive implementation utilizing all electrode sites, a broader feature library, and automated multi-feature fusion will be required to fully judge the method's potential for predicting seizures.     

Adjunctive imipramine for dysphoric schizophrenic patients with past histories of cannabis abuse.

1. Twenty-one schizophrenic or schizoaffective patients with histories of cannabis abuse and operationally-defined syndromes of post-psychotic depression completed a double-blind trial of adjunctive imipramine added to their on-going medication regimen of fluphenazine decanoate and benztropine. 2. The imipramine-treated patients had superior global outcome. 3. Subscales suggested that specific improvement occurred in imipramine-treated patients in the domain of depression-like features. 4. Psychotic symptomatology was not found to be exacerbated by the imipramine.