Coronary Sinus Aneurysm and Left Ventricular‐Coronary Sinus Fistula. Implantation of CRT Device

We describe a 72‐year‐old man referred for implantation of a cardiac resynchronization therapy device who had previously undergone repeated operations to replace the mitral valve. Retrograde venography of the coronary sinus (CS) to implant the left ventricular (LV) pacing lead revealed aneurysmal dilatation of the CS with LV‐CS fistula that hindered—but did not prevent—complete implantation of the system. (PACE 2013; 36:e38–e40)     

Treatment of Hereditary Spherocytosis in Peromyscus by Radiation and Allogeneic Bone Marrow Transplantation

An inherited disease of the bone marrow identical in its pathophysiologyto human hereditary spherocytosis has been described in the deer mouse,Peromyscus maniculatus. As Peromyscus are not inbred and of distinct individually-specific histocompatibility, they provide an experimental model system for the use of hemopoietic allotransplantation in the treatment of hereditary diseases of the erythron. Ninety adult mice were exposed to otherwise 100per cent lethal doses of x-rays and then inoculated intravenously with 20 to60 million nucleated marrow cells. Marrow was transplanted on a one-to-onedonor recipient basis in four combinations of phenotypes: normal to normal;spherocytic to normal; spherocytic to spherocytic; and normal to spherocytic.Mortality and pathology were similar in all groups. Thirty per cent of the hostsdied as a direct result of the irradiation within 20 days. Another 30 per centsubsequently succumbed to secondary disease presumably of graft-against-hostorigin, bringing the overall mortality to 60 per cent at the end of 10 weeks. At3 months, however, the hematologic status of the survivors, nearly withoutexception, was of donor phenotype: Genetically spherocytic recipients of normalmarrow contained normal red cells; conversely, wild type recipients of spherocytic marrow had assumed the mutant phenotype. Evidence of chronic grafthost interaction was obtained. By 7 months, six mice in the spherocyticto normal transplant group had reassumed the host hematologic phenotype, but only one animal in the normal to spherocytic group reverted to themutant phenotype.

Submitted on May 24, 1966 Accepted on July 18, 1966     

MAST CELL DISTRIBUTION,ACTIVATION, AND PHENOTYPE IN ATHEROSCLEROTIC LESIONS OF HUMAN CAROTID ARTERIES

Immunohistochemical staining for mast cell tryptase and chymase was used to examine the distribution, activation, and tryptase/chymase phenotype of mast cells (MCs) in 250 samples of atherosclerotic lesions (type I to VI) of human carotid arteries. Dual immunolocalization and histochemical techniques were used to identify the associations of MCs with macrophages, smooth muscle cells, and extracellular matrix components. Whereas normal carotid arteries contained very few MCs within the intima, atherosclerotic lesions showed increased MC numbers with variable focal accumulations. MCs were identifiable from the earliest stages of atherosclerosis, and especially at the shoulder regions of the fully formed atheroma. They were observed in close association with macrophages (HAM56 positive) and extracellular lipid, as well as at sites of foam cell formation. MCs and diffuse tryptase staining were also evident within sites of new calcification and around small calcified deposits. Extensive MC activation/degranulation, as judged by diffuse extracellular tryptase staining, was a common feature of the advanced atherosclerotic plaques complicated by fissure, haemorrhage, and thrombus formation. Moreover, such sites of extracellular MC tryptase were often associated with localized oedema and disruption of the stromal matrix. MCs which contained both tryptase and chymase (the MC_TC phenotype) represented approximately 80–95 per cent of all MCs. These studies are the first to demonstrate significant numbers and focal accumulations of MCs in all developmental stages of atherosclerotic carotid arteries. Since MCs contain or express a variety of potent mediators, their release could profoundly influence the development and pathological complications of atherosclerotic plaques. © 1997 John Wiley & Sons, Ltd.     

Sex and Intrauterine Position Influence the Size of the Gerbil Hippocampus

Sex differences in home range size and spatial ability are predictive of sex differences in the relative size of the hippocampus in rodents. Such differences in behavior and hippocampal volume are presumed to be, in part, the result of differences in perinatal exposure to hormones. We predicted from differences in the size of home ranges of male and female Mongolian gerbils (Meriones unguiculatus) in the wild that the hippocampus of male gerbils would be relatively larger than that of females. We examined the effect of prenatal hormonal influences on hippocampal size by comparing hippocampal volume of males and females from 2F and 2M intrauterine positions to that of randomly selected males and females. We found that, as predicted, randomly selected males had a significantly larger hippocampus, relative to telencephalon, than did randomly selected females. However, males and females from 2F and 2M intrauterine positions did not differ in relative hippocampal size. Possible explanations for the absence of a sex difference in hippocampal size in male and female gerbils from 2F and 2M intrauterine positions are discussed.     

Unexpected Immunoresponse to Gal and APA Antigens in Diabetic Type 1 Patients Receiving Neonatal Pig Islets After 6 Years

Cotransplantation of porcine islets and Sertoli cells into preimplanted subcutaneous devices improve metabolic control in type 1 diabetic patients, and survive grafted for more than 4 years. We report here, further assessment of the endocrine and porcine nature of the surviving cells and the immune responses elicited toward Gal α(1,3)-Gal β(1,4)-GlcNAc (Gal) antigen in patients who received a second and third transplants. No immunosuppressive drugs were administered. We were able to immunostain insulin- and glucagon-positive cells in all biopsies of patients and Sertoli cell markers in 60.9% of biopsies. Additionally, all biopsies tested, amplified the porcine COII gene. Patients demonstrated an increase in antipig antibodies in response to the first transplant with a decreasing response toward the second and third transplants. In all transplants, the IgG levels promptly returned to basal values after 3–4 months. The long-term survival of porcine cells and the reduced humoral immune response to multiple transplants indicate a form of tolerance. We have not been able to find CD25-positive cells, indicating that it is probably an immune accommodation of the graft.     

A new metric for quantifying performance impairment on the psychomotor vigilance test

We have developed a new psychomotor vigilance test (PVT) metric for quantifying the effects of sleep loss on performance impairment. The new metric quantifies performance impairment by estimating the probability density of response times (RTs) in a PVT session, and then considering deviations of the density relative to that of a baseline‐session density. Results from a controlled laboratory study involving 12 healthy adults subjected to 85 h of extended wakefulness, followed by 12 h of recovery sleep, revealed that the group performance variability based on the new metric remained relatively uniform throughout wakefulness. In contrast, the variability of PVT lapses, mean RT, median RT and (to a lesser extent) mean speed showed strong time‐of‐day effects, with the PVT lapse variability changing with time of day depending on the selected threshold. Our analysis suggests that the new metric captures more effectively the homeostatic and circadian process underlying sleep regulation than the other metrics, both directly in terms of larger effect sizes (4–61% larger) and indirectly through improved fits to the two‐process model (9–67% larger coefficient of determination). Although the trend of the mean speed results followed those of the new metric, we found that mean speed yields significantly smaller (～50%) intersubject performance variance than the other metrics. Based on these findings, and that the new metric considers performance changes based on the entire set of responses relative to a baseline, we conclude that it provides a number of potential advantages over the traditional PVT metrics.     

REDIRECTING T LYMPHOCYTE SPECIFICITY USING T CELL RECEPTOR GENES

Redirecting T cells by transferring T cell receptor (TCR) genes from tumor-associated antigen (TAA)-reactive T cell clones into human peripheral blood lymphocytes (PBL) has therapeutic potential for the treatment of diseases, including cancer. T cell specificity can be altered using retroviruses encoding TCR &#102 and TCR &#103 chain genes, or chimeric immunoglobulin (cIg) genes containing signaling domains of CD3 &#145 or Fc &#108 RI- &#110. This review evaluates recent studies using TCRs and cIgs to redirect T cell specificity and discusses some of the technical and biological hurdles that need to be addressed before these approaches can be successfully used to treat patients.