Diffuse type of senile plaques in the cerebellum of Alzheimer-type dementia demonstrated byβ protein immunostain

Summary We studied senile plaques (SP) in the cerebella of six autopsied subjects with Alzheimer-type dementia (ATD) and ten non-ATD autopsied subjects between the ages of 78 and 90. Neither SP nor amyloid angiopathy (AA) was observed in any of the non-ATD subjects. In the four of the six ATD subjects, diffuse plaques in the molecular layer were seen as ill-defined areas of fine fibrillar materials by protein immunostaining with formic acid pretreatment, the modified Bielschowsky stain, and periodic acid-methenamine silver (PAM) stain. The plaques were not visible with Bodian, Congo red, or periodic acid-Schiff stains. Compact plaques in the Purkinje cell or in the granular cell layers were found in three of the six subjects. Their amyloid core was often surrounded by areolar amyloid deposits. AA was observed in three of the six subjects. The argyrophilia of the diffuse and compact plaques, demonstrated by the modified Bielschowsky and PAM stains, became undetectable when the sections were first treated with formic acid. Such treatment made the plaques immunoreactive with protein antiserum. The findings suggested that cerebellar diffuse plaques and compact plaques consist mainly of an amyloid component, and are characteristic of ATD.     

β-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

The use of 15-p-iodophenyl--methyl-pentadecanoic acid (Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioctivity (residue curves) were obtained following bolus injections of both Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, Me-IPPA kinetics were insenstive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significatly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond Me-IPPA-CoA in the oxidative pathway.     

Patellofemoral joint cartilage restoration with particulated juvenile allograft in patients under 21 years old

BackgroundPatellofemoral joint cartilage defects are difficult to treat due to their unique thickness and topography.PurposeTo report the postoperative outcomes of patients age 21 and younger treated with particulated juvenile allograft cartilage (PJAC) for full-thickness cartilaginous defects of the patellofemoral joint. The primary aim was to report surgical outcomes and complication rates, as well as return to sport activity. A secondary aim was to provide objective scores of defect restoration by magnetic resonance imaging (MRI) assessment.MethodsA retrospective review of all PJAC cases conducted between 2012 and 2019 at a single tertiary care urban musculoskeletal institution was conducted. Patients 21 years old or younger with minimum clinical follow up of 1 year and postoperative MRI at a minimum of 6 months were included. Cartilage restoration by MRI was independently assessed using the International Cartilage Repair Society’s (ICRS) standardized system.ResultsThirty four patients, 36 knees, were included, with mean age 16.1 ± 3.1 years old. Return to sport rate among patients who participated in a sport preoperatively was 100%. On independent MRI assessment, two thirds of defects achieved an overall grade of normal or nearly normal, while 28 patients (78%) had majority defect fill. Primary graft failure occurred in two cases and one patient experienced a surgical complication.ConclusionRestoration of patellofemoral chondral defects in young patients with particulated juvenile allograft results in satisfactory short-term outcomes and postoperative MRI appearance, along with high rates of return to sport and low rate of complications and graft failure.What is known about the subject: Patellofemoral joint cartilage defects are difficult to treat due to their unique thickness and topography. Several cartilage restoration techniques are available, but these rarely achieve the same mechanical properties as native hyaline cartilage. PJAC is a cell-based technique that has demonstrated promise since its introduction in 2007.What this study adds to existing knowledge: This series of patients adds the largest single cohort of pediatric and adolescent patients who receive PJAC for defects of the patellofemoral joint. Surgeons treating patients in this age group should be aware of every technique, and their respective outcomes.     

Effect of amino acid derivatives of β-carboline-3-carboxylate on behavior in rats

Brain Research Institute, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR O. S. Adrianov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 5, pp. 586–587, May, 1989.     

Predicting development of sustained unresponsiveness to milk oral immunotherapy using epitope-specific antibody binding profiles

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CR-lipped bearing is an adequate functional solution to patients with perioperative excessive laxity in cruciate retaining total knee arthroplasty

BackgroundThe cruciate retaining lipped (CR-lipped) bearing is designed to provide more anterior-posterior (AP) stability and could be employed to resolve excessive intraoperative laxity during the cruciate retaining TKA (CR-TKA). The aim of the study was to determine whether the CR-lipped bearing in CR-TKAs with a perioperative excessive laxity allows equivalent functional results as compared to the standard CR articulation.MethodsA cohort of 111 TKAs with CR-lipped bearings was matched to a cohort of conventional CR bearings regarding age and sex. The CR-lipped bearing was used in patients with excessive knee AP laxity and the regular CR bearing was used in patients without excessive AP laxity during TKA. Various PROMs (WOMAC, KSS, SF-36) were assessed preoperatively and at 5-years postoperative in combination with revision rate and Range of Motion (ROM).ResultsPROMs did not differ significantly between both groups 5-years postoperatively. Mean ROM (flexion) 5-years postoperatively was not significantly different. The implant survivorship was 100% for both cohorts with revision for any reason as end point.ConclusionBased on these results, the CR-lipped bearing is a safe and effective solution for mild interoperatively assessed PCL laxity during CR-TKA without loss of function or decreased survivorship at 5 years. Peroperative conversion to a PS-TKA in order to obtain satisfactory functional scores might therefore not be necessary when mild PCL laxity is observed during surgery. Further research should focus on verifying this approach and longer follow-up is needed to generate data on long term survivorship.Level of evidenceLevel IV therapeutic, retrospective, cohort study.     

Anti-AT1R autoantibodies and prediction of the severity of Covid-19

The stimulation of AT1R (Angiotensin II Receptor Type 1) by Angiotensin II has, in addition to the effects on the renin-angiotensin system, also pro-inflammatory effects through stimulation of ADAM17 and subsequent production of INF-gamma and Interleukin-6. This pro-inflammatory action stimulate the cytokine storm that characterizes the most severe forms of SARS-CoV-2 infection. We studied the effect of AT1Rab on the AT1R on 74 subjects with SARS-CoV-2 infection with respiratory symptoms requiring hospitalization. We divided the patients into 2 groups: 34 with moderate and 40 with severe symptoms that required ICU admission. Hospitalized subjects showed a 50% reduction in the frequency of AT1Rab compared to healthy reference population. Of the ICU patients, 33/40 (82.5%) were AT1Rab negative and 16/33 of them (48.5%) died. All 7 patients positive for AT1Rab survived. These preliminary data seem to indicate a protective role played by AT1R autoantibodies on inflammatory activation in SARS-CoV-2 infection pathology.     

The molecular basis for inherited bullous diseases

In the past 5 years enormous progress have been made in our understanding of the molecular basis for a number of inherited skin diseases characterized by easy blistering of the skin and the mucous membranes after minor physical trauma. This increased fragility of the skin or its appendages is due to molecular defects in genes coding for different intra- and extracellular structural proteins which are responsible for mechanical strength at their sites of expression. These diseases encompass the group of epidermolysis bullosa and disorders of cornification such as bullous forms of ichthyosis, palmoplantar keratoderma, and pachyonychia congenita. On the basis of clinical, morphological, and ultrastructural observations the epidermolysis bullosa group has been divided into three major categories. In epidermolysis bullosa simplex blister formation appears within the basal cell layer of the epidermis, and many mutations have been found in the genes of keratin 5 and 14 which are both expressed in basal keratinocytes. Epidermolytic hyperkeratosis leads to an epidermal separation in the suprabasal cell layers. In these patients numerous point mutations have now been described in the suprabasally expressed genes of keratin 1 and 10. In ichthyosis bullosa of Siemens blisters occur in the more upper suprabasal epidermis coincidental with the expression of keratin 2e, and mutations have been detected in the corresponding gene. In epidermolytic palmoplantar hyperkeratosis the suprabasal epidermal splitting is restricted to palms and soles of the patient. In keratin 9, which reveals such an exclusive expression pattern, molecular defects have indeed been recognized. Most recently in two different clinical subtypes of pachyonychia congenita, which is characterized by defective nails and focal palmoplantar hyperkeratosis, point mutations have been found in the genes coding for keratins 6, 16, and 17. In junctional epidermolysis bullosa the separation takes place within the dermal-epidermal basement membrane at the level of the lamina lucida, and mutations have been found in three genes coding for different laminin chains, in the ₄ gene of ₆₄ integrin, and in the gene of collagen XVII. In dystrophic epidermolysis bullosa the tissue separation occurs beneath the basement membrane within the papillary dermis at the level of the anchoring fibrils, and several mutations have been identified in the collagen VII gene. The rapid unraveling of molecular defects in these disabling or even lethal inherited skin diseases makes possible a more precise and earlier prenatal diagnosis, creates new options for suitable therapeutic regimens, and even offers the hope of curing these diseases by means of somatic cell gene therapy.Abbreviations BM Basement membrane - BPAg Bullous pemphigoid antigen - DEB Dystrophic epidermolysis bullosa - EB Epidermolysis bullosa - EBS Epidermolysis bullosa simplex - EHK Epidermolytic hyperkeratosis - EPPK Epidermolytic palmoplantar keratoderma - IBS Ichthyosis bullosa of Siemens - JEB Junctional epidermolysis bullosa - KIF Keratin intermediate filaments - NC Noncollagenous domain - NEPPK Nonepidermolytic palmoplantar keratoderma - PC Pachyonychia congenita     

A Computer Reconstruction of the Entire Coronary Arterial Tree Based on Detailed Morphometric Data

A rigorous analysis of blood flow must be based on the branching pattern and vascular geometry of the full vascular circuit of interest. It is experimentally difficult to reconstruct the entire vascular circuit of any organ because of the enormity of the vessels. The objective of the present study was to develop a novel method for the reconstruction of the full coronary vascular tree from partial measurements. Our method includes the use of data on those parts of the tree that are measured to extrapolate the data on those parts that are missing. Specifically, a two-step approach was employed in the reconstruction of the entire coronary arterial tree down to the capillary level. Vessels > 40 μm were reconstructed from cast data while vessels < 40 μm were reconstructed from histological data. The cast data were reconstructed one-bifurcation at a time while histological data were reconstructed one-sub-tree at a time by “cutting” and “pasting” of data from measured to missing vessels. The reconstruction algorithm yielded a full arterial tree down to the first capillary bifurcation with 1.9, 2.04 and 1.15 million vessel segments for the right coronary artery (RCA), left anterior descending (LAD) and left circumflex (LCx) trees, respectively. The node-to-node connectivity along with the diameter and length of every vessel segment was determined. Once the full tree was reconstructed, we automated the assignment of order numbers, according to the diameter-defined Strahler system, to every vessel segment in the tree. Consequently, the diameters, lengths, number of vessels, segments-per-element ratio, connectivity and longitudinal matrices were determined for every order number. The present model establishes a morphological foundation for future analysis of blood flow in the coronary circulation.