Undoing Institutional and Racial Trauma Through Interprofessional, Trauma-Informed Education.

Trauma-informed care is a transdisciplinary framework that existed well before 2020, but it is now more imperative to teach it and incorporate it into medical education. This paper describes a novel interprofessional curriculum and its focus on trauma-informed care-notably, including institutional and racial trauma-that was implemented by Yale University for medical, physician associate, and advanced practice registered nursing students.

Etoposide induction of tumor immunity in Lewis lung cancer.

Purpose: To determine if the antineoplastic effect of etoposide includes alteration in Lewis lung cancer cells which evoke an immunologic response in C57B1/6 host mice.

Methods And Results: Of C57B1/6 mice injected with 10(6) Lewis lung cancer (3LL) cells followed by treatment with a single 50 mg/kg dose of etoposide (VP-16), 60% survived over 60 days, in contrast to untreated control mice which died within 30 days. Approximately 40% of surviving mice rejected a subsequent challenge with 3LL.

Naturally occurring insulin autoantibodies in neonates of normal pregnancies and their relationship to insulinemia and birth weight.

Objective: The objectives of this study were to determine whether insulin autoantibodies are present in umbilical cord blood from normal pregnancies, determine whether cord blood insulin autoantibody levels correlate with respective maternal levels at delivery, determine whether cord blood insulin autoantibody levels are related to cord blood or maternal insulin levels, and to determine what relationship neonatal birth weight has with either cord blood insulin autoantibody and insulin levels or maternal insulin autoantibody and insulin levels.

Study Design: Paired umbilical cord and maternal serum samples were taken from 70 normal subjects at delivery. Measurements of serum insulin autoantibody (competitive charcoal radiobinding assay) and insulin (radioimmune inhibition assay) levels were performed.

Differences in humoral insulin-antibody response among inbred Lou/M rats and epitope presentation differences in ELISA and radioimmune titration.

Insulin antibodies were not detected in an insulin-capture enzyme-linked immunosorbent assay (ELISA), but they were easily detected in an insulin-copolymer-capture ELISA. Thus, there is a high degree of steric hindrance because of the proximity of the epitopes on the insulin monomer. This is circumvented by substituting an insulin copolymer for insulin in the capture ELISA.

Effect of isologous and autologous insulin antibodies on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lou/M rats.

The in vivo bioavailability, distribution, and metabolic fate of 125I-labeled insulin complexed to isologous and autologous antibodies were studied in inbred Lou/M rats. There was an impaired bioavailability of the 125I-insulin bound to the isologous and autologous antibodies. Very little of the 125I-insulin in these immune complexes could bind to insulin receptors on hepatocytes or renal tubular cells and be degraded, because the amounts of 125I from degraded 125I-insulin in the blood or secreted into the stomach were markedly attenuated in both cases for at least 30 min after injection.

Effect of IgG subclasses on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lewis rats.

The bioavailability, distribution, and metabolic fate of 125I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min.

Scintigraphic distribution of complexes of antiinsulin antibodies and 123I-insulin. In vivo studies in rats.

Clearance of immune complexes made of antiinsulin antibodies and 123I-insulin was studied with scintillation scanning in anesthetized rats. Complexes made with purified guinea pig antiinsulin IgG2 (cytophilic isotype) were rapidly cleared by the liver whereas those made with IgG1 remained in the plasma, as did 123I-labeled IgG1 or IgG2 of control animals. Hepatic clearance of insulin-antiinsulin IgG complexes was not inhibited by either an excess of insulin or decomplementation, thereby ruling out interaction with insulin and C3b receptors.

Insulin resistance in total lipodystrophy: evidence for a pre-receptor defect in insulin action.

The cause of insulin resistance in lipodystrophic diabetes is unknown but has generally been ascribed to dysfunction at either the receptor or post receptor level. In a 14 year-old girl with total acquired lipodystrophy, subcutaneous and intravenous insulin requirements approximated 600 units daily. However, circulating total and free insulin levels were not increased, and during testing by the euglycemic clamp method, the glucose response to increasing free insulin concentrations was within the range found in eight subjects with insulin-dependent diabetes.

Immunologic implications of insulin delivery and the role of immune complexes in diabetic sequelae.

Insulin has been studied as a model antigen in relation to the functions of immune sensing, modulating, and effector responses to antigens. Each of these immune responses has been associated to the major histocompatibility complex in animals and man. This report summarizes key features of established involvement of antigens in the immune response to various insulin preparations.

Cardiovascular complications.

This report summarizes the current state of knowledge concerning the cardiovascular system in various animal models of diabetes and presents their major strengths and weaknesses for studying the important research questions in the field. Nonhuman primates have many desirable features for studies on the macrovascular and cardiac complications of the disease as well as risk factor alterations, but their availability, cost, and maintenance present practical disadvantages. The spontaneous rodent models of diabetes currently are not considered very useful for cardiovascular research, but they have not been well characterized with respect to most aspects of their cardiovascular system.

Effects of insulin on wound healing in diabetic mice.

In the present study wound healing was examined in normal C57B1/6 male mice, diabetic mice, non-treated; and in diabetic mice treated with insulin. Small dermal wounds were made in the ears of the mice 40 h after the initial injection of insulin or vehicle alone. All animals were biopsied 8 h later.

Wound healing in normal and diabetic Chinese hamsters.

Wound healing was examined in normal and diabetic, non ketotic Chinese hamsters by morphological and morphometric methods. Dermal, perforating wounds were made in the ears of the hamsters and the response to injury was evaluated in tissue biopsies. The response in normal hamsters was characterized by vascular and cellular migration and pronounced infiltration of polymorphonuclear leukocytes into the area closest to the wound (zone 1).

The effect of antisera to insulin, 2-deoxyglucose-induced hyperglycemia, and starvation on wound healing in normal mice.

Wound healing was examined in normal C57BL/6 male mice treated with antiserum to insulin or 2-deoxyglucose (2-DG) and in mice starved for 33 h. Hyperglycemia was induced after antiserum or 2-DG treatment; the blood glucose was lowered in the starved mice when compared with controls. Small dermal wounds were made in the ears of the mice 1 h after the initial injection of antisera or 2-DG.

Phagocytosis and chemotaxis of macrophages from normal and diabetic mice.

Experiments were designed to study the chemotaxis and phagocytic functions of mouse peritoneal exudate macrophages from normal and chronic diabetic mice. There was no difference in the total number of white blood cells (WBC's), or the total number of any one type of leukocyte (i.e.

Decreased incidence of HLA-A11 and increased incidence of HLA-B8 in a North American population of insulin dependent diabetics.

Seventy-four North American Caucasian insulin dependent diabetics are presented and compared to 100 healthy controls relative to HLA-A and B locus antigens. A highly significant increase in the frequency of HLA-B8 was found (p < 0.01, relative risk 3.

Induction of hyperglycemia with insulin antibodies to B-chain determinants.

Insulin antibodies measured by a radioimmune method (ABR) are significantly better inducers of hyperglycemia than are insulin antibodies measured by an immune hemolysis method (ABH) when injected intraperitoneally into mice. The ability to induce hyperglycemia by an insulin antiserum can be predicted by the titer of ABR measured. ABR interact in vitro with determinants severely perturbed on nickel-insulin, partially perturbed on proinsulin and desasparagine-desalanine insulin, and unaffected on zinc-insulin or zinc-free monocomponent insulin.

The effect of zinc on insulin metabolism.

Experiments were designed to study the effect of Zn on in vivo and in vitro insulin metabolism. The in vivo experiments involved pretreating mice with either Zn or Na, followed by ip [125I]iodoinsulin injection. Pretreatment of mice with Zn resulted in an accelerated and increased magnitude of binding of [125I]iodoinsulin to the liver compared to mice pretreated with Na.

Effects of zinc ion on the conformation of antigenic determinants on insulin.

Comparison of c.d. spectra of Zn-insulin with Zn2+-free insulin demonstrated significant differences.

Structural studies of insulin and insulin derivatives using various immunologic indicators and antibody populations.

These studies suggest that the immunologic indicator in the radioimmune assay, 125I-iodoinsulin, selects antibody populations from within the antiserum that interact with determinants distant from the solvent surface on the insulin molecule to which iodine is substituted. Evidence is presented that the connecting peptide of proinsulin is in close proximity to regions on the solvent surface of the A-chain of insulin that include the tyrosyl residues at A-14 and A-19. A marked immunologic cross-reaction between derivatives of insulin with perturbations in the regions of tyrosyl A-14 and A-19 was noted in the radioimmune assay employing desalanine-(B-30)-desasparagine-(A-21)-insulin antiserum.

Wound healing: a model for the study of diabetic angiopathy.

Wound healing as a model for diabetic angiopathy has been studied by light and electron microscopy. Biochemical studies of the rate of incorporation of 3H-proline and 3H-thymidine into collagen and DNA, respectively, have confirmed the morphologic observations. In both the normal and the diabetic, there was a marked decrease in the rate of collagen and DNA synthesis, suggesting that most of the cells in the biopsies were stunned by the injury and ceased DNA replication during the initial phase.

[127-I]- or carrier-free [125-I]monoiodoinsulin.

Insulin was enzymatically moniodinated with 127-I or 125-I, and an improved method of purification by anion exchange chromatography was employed. (127-I)Monoiodoinsulin was identified by spectrophotometric analysis and its molar extinction coefficient determined to be 6.31 times 10-3 M-1 cm minus 1.