Interstitial Capillary in Normal and in Transplanted Kidneys: An Ultrastructural Study

Knowledge about the normal structure and pathology of interstitial capillary is limited. Splitting and multilayering of the basal membrane (BM), as a marker of chronic rejection, has been published in association with transplant glomerulopathy. The authors investigated the ultrastructural features of the interstitial capillary basal membrane in normal (15 biopsies) and in transplanted kidneys (27 biopsies from 21 patients), expressing transplant glomerulopathy (8 biopsies from 6 patients), acute tubulo-interstitial rejection (9 biopsies from 6 patients), and recurrent or de novo glomerulonephritis (10 biopsies from 8 patients). All biopsies were fixed in 1%OsO 4, embedded in Epon, and examined by electron microscope. Measurements of the interstitial capillary BM were made. The BM of interstitial capillary of intact kidney was a homogenous continuous structure, 88 nm in width on average. Thickening with diffuse multilayering of BM was most intensive in patients with transplant glomerulopathy, and much less intensive in patients with acute tubulointerstitial rejection and in patients with recurrent or de novo glomerulonephritis. These findings may provide the first information about the morphology of the normal basal lamina of interstitial capillary and support the diagnostic value of interstitial capillary changes in chronic rejection.     

On hemispheric specialisation and visual field effects in the perception of print: A comment on Jordan,Patching, and Thomas

Introduction Due to structural characteristics of the visual pathways, stimuli that are presented in the right half of the visual field (RVF) are initially projected to the left cerebral hemisphere, while those presented in the left half of the visual field (LVF) are projected to the right cerebral hemisphere. This anatomical feature has frequently been taken to support the notion that the well-documented RVF advantage in recognising printed words is a reflection of functional differences between the two hemispheres; notably that of the dominance of the left hemisphere for processing language. Word stimuli that are sent straight to the left hemisphere are believed to profit from more efficient processing than those sent initially to the right hemisphere, because the latter stimuli must follow a longer and more noisy pathway before reaching the language-dominant hemisphere. In the work by Jordan, Patching, and Thomas (2003) the above notion is further developed to speculate that the point of entry of visual information into the cortex may determine the procedure that will underlie the ensuing word recognition process: "... the left hemisphere can process words by mapping orthographic information in parallel onto lexical entries whereas the right hemisphere has a more rudimentary process, that can only map orthographic information sequentially" (p. 50).     

SARS-CoV-2-reactive T-cell receptors isolated from convalescent COVID-19 patients confer potent T-cell effector function

Both B cells and T cells are involved in an effective immune response to SARS-CoV-2, the disease-causing virus of COVID-19. While B cells—with the indispensable help of CD4⁺ T cells—are essential to generate neutralizing antibodies, T cells on their own have been recognized as another major player in effective anti-SARS-CoV-2 immunity. In this report, we provide insights into the characteristics of individual HLA-A*02:01- and HLA-A*24:02-restricted SARS-CoV-2-reactive TCRs, isolated from convalescent COVID-19 patients. We observed that SARS-CoV-2-reactive T-cell populations were clearly detectable in convalescent samples and that TCRs isolated from these T cell clones were highly functional upon ectopic re-expression. The SARS-CoV-2-reactive TCRs described in this report mediated potent TCR signaling in reporter assays with low nanomolar EC50 values. We further demonstrate that these SARS-CoV-2-reactive TCRs conferred powerful T-cell effector function to primary CD8⁺ T cells as evident by a robust anti-SARS-CoV-2 IFN-γ response and in vitro cytotoxicity. We also provide an example of a long-lasting anti-SARS-CoV-2 memory response by reisolation of one of the retrieved TCRs 5 months after initial sampling. Taken together, these findings contribute to a better understanding of anti-SARS-CoV-2 T-cell immunity and may contribute to paving the way toward immunotherapeutics approaches targeting SARS-CoV-2.     

Initial results after combined repair of aortic arch aneurysms by sequential transposition of the supra-aortic branches and consecutive endovascular stent-graft placement

Background

To evaluate safety and efficacy of a combined repair of aortic arch aneurysms by sequential transposition of the supra-aortic branches and endovascular stent-graft placement.

Methods

Between October 2002 and September 2003, 5 patients (mean age, 79.5 years) presented with aortic arch aneurysms involving the origin of the left carotid artery. Treatment was made by sequential transposition of the left carotid artery into the brachiocephalic trunk and transposition of the left subclavian artery into the already transposed left common carotid artery with consecutive endovascular stent-graft placement into the aortic arch.

Results

All patients survived both procedures. At completion angiography, a small type 1a endoleak was observed in 1 patient. After 1 week, the patient was readmitted for completion three-dimensional computed tomographic scan. The leak had already occluded spontaneously. Mean follow-up was 10 months (range, 4 to 16 months). At follow-up, all patients had normal computed tomographic scans with regular perfusion of the supra-aortic branches without any signs of endoleaks.

Conclusions

Combined repair of aortic arch aneurysms by sequential transposition of the supra-aortic branches with consecutive endovascular stent-graft placement is feasible. Extended application of this technique will enable safe and effective treatment of a highly selected subgroup of patients with aortic aneurysms by avoiding conventional arch aneurysm repair in deep hypothermia and circulatory arrest.     

The roles of TRPV1, TRPA1 and TRPM8 channels in chemical and thermal sensitivity of the mouse oral mucosa

Spices in food and beverages and compounds in tobacco smoke interact with sensory irritant receptors of the transient receptor potential (TRP) cation channel family. TRPV1 (vanilloid type 1), TRPA1 (ankyrin 1) and TRPM8 (melastatin 8) not only elicit action potential signaling through trigeminal nerves, eventually evoking pungent or cooling sensations, but by their calcium conductance they also stimulate the release of calcitonin gene‐related peptide (CGRP). This is measured as an index of neuronal activation to elucidate the chemo‐ and thermosensory transduction in the isolated mouse buccal mucosa of wild types and pertinent knockouts. We found that the lipophilic capsaicin, mustard oil and menthol effectively get access to the nerve endings below the multilayered squamous epithelium, while cigarette smoke and its gaseous phase were weakly effective releasing CGRP. The hydrophilic nicotine was ineffective unless applied unprotonated in alkaline (pH9) solution, activating TRPA1 and TRPV1. Also, mustard oil activated both these irritant receptors in millimolar but only TRPA1 in micromolar concentrations; in combination (1 mm ) with heat (45 °C), it showed supraadditive, that is heat sensitizing, effects in TRPV1 and TRPA1 knockouts, suggesting action on an unknown heat‐activated channel and mustard oil receptor. Menthol caused little CGRP release by itself, but in subliminal concentration (2 mm ), it enabled a robust cold response that was absent in TRPM8^?/? but retained in TRPA1^?/? and strongly reduced by TRPM8 inhibitors. In conclusion, all three relevant irritant receptors are functionally expressed in the oral mucosa and play their specific roles in inducing neurogenic inflammation and sensitization to heat and cold.     

Mineralocorticoid receptor and heat shock protein expression levels in peripheral lymphocytes from war trauma-exposed men with and without PTSD

Alterations in the number and functional status of mineralocorticoid (MR) and glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor and heat shock protein expression levels, and related them with war trauma exposure, PTSD and resilience to PTSD. Relative levels of MR, Hsp90 and Hsp70 were determined by immunoblotting in lymphocytes from war trauma-exposed men with current PTSD (current PTSD group, n=113), with life-time PTSD (life-time PTSD group, n=61) and without PTSD (trauma control group, n=88), and from non-traumatized healthy controls (healthy control group, n=85). Between-group differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed. The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control and healthy control groups. On the other hand, GR level was correlated only with Hsp90 level, and this correlation was evident in current PTSD and trauma control groups. In conclusion, PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins.