bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression, Linkage, and Polymorphism of MHC-Related Genes in Rainbow Trout,Oncorhynchus mykiss
Authors: Hansen John D. , Strassburger Pamela , Thorgaard Gary H. , Young William P. , Du Pasquier Louis
Published: December 2022

The architecture of the MHC in teleost fish, which display a lack of linkage between class I and II genes, differs from all other vertebrates. Because rainbow trout have been examined for a variety of immunologically relevant genes, they present a good teleost model for examining both the expression and organization of MHC-related genes. Full-length cDNA and partial gDNA clones for proteasome δ, low molecular mass polypeptide (LMP) 2, TAP1, TAP2A, TAP2B, class Ia, and class IIB were isolated for this study. Aside from the expected polymorphisms associated with class I genes, LMP2 and TAP2 are polygenic. More specifically, we found a unique lineage of LMP2 (LMP2/δ) that shares identity to both LMP2 and δ but is expressed like the standard LMP2. Additionally, two very different TAP2 loci were found, one of which encodes polymorphic alleles. In general, the class I pathway genes are expressed in most tissues, with highest levels in lymphoid tissue. We then analyzed the basic genomic organization of the trout MHC in an isogenic backcross. The main class Ia region does not cosegregate with the class IIB locus, but LMP2, LMP2/δ, TAP1A, and TAP2B are linked to the class Ia locus. Interestingly, TAP2A (second TAP2 locus) is a unique lineage in sequence composition that appears not to be linked to this cluster or to class IIB. These results support and extend the recent findings of nonlinkage between class I and II in a different teleost order (cyprinids), suggesting that this unique arrangement is common to all teleosts.
CD28, IL-2-Independent Costimulatory Pathways for CD8 T Lymphocyte Activation
Authors: Sepulveda Homero , Cerwenka Adelheid , Morgan Tammy , Dutton Richard W.
Published: December 2022

We investigate, here, the mechanism of the costimulatory signals for CD8 T cell activation and confirm that costimulation signals via CD28 do not appear to be required to initiate proliferation, but provide survival signals for CD8 T cells activated by TCR ligation. We show also that IL-6 and TNF-α can provide alternative costimulatory survival signals. IL-6 and TNF-α costimulate naive CD8 T cells cultured on plate-bound anti-CD3 in the absence of CD28 ligation. They act directly on sorted CD8-positive T cells. They also costimulate naive CD8 T cells from Rag-2-deficient mice, bearing transgenic TCRs for HY, which lack memory cells, a potential source of IL-2 secretion upon activation. IL-6 and TNF-α provide costimulation to naive CD8 T cells from CD28, IL-2, or IL-2Rα-deficient mice, and thus function in the absence of the B7-CD28 and IL-2 costimulatory pathways. The CD8 T cell generated via the anti-CD3 plus IL-6 and TNF-α pathway have effector function in that they express strong cytolytic activity on Ag-specific targets. They secrete only very small amounts of any of the cytokines tested upon restimulation with peptide-loaded APC. The ability of the naive CD8 T cells to respond to TCR ligation and costimulatory signals from IL-6 and TNF-α provides a novel pathway that can substitute for signals from CD4 helper cells or professional APC. This may be significant in the response to viral Ags, which can be potentially expressed on the surface of any class I MHC-expressing cell.
Nickel Allergy in Mice: Enhanced Sensitization Capacity of Nickel at Higher Oxidation States
Authors: Artik Suzan , von Vultée Christian , Gleichmann Ernst , Schwarz Thomas , Griem Peter
Published: December 2022

Attempts to induce contact hypersensitivity to nickel in mice using, e.g., Ni(II)Cl2 often failed. Here, we report that sensitization was achieved by injecting Ni(II)Cl2 in combination with either CFA or an irritant, such as SDS and PMA, or IL-12, or by administering nickel at higher oxidation states, i.e., Ni(III) and Ni(IV). Although Ni(II), given alone, was ineffective in T cell priming, it sufficed for eliciting recall responses in vivo and in vitro, suggesting that Ni(II) is able to provide an effective signal 1 for T cell activation, but is unable to provide an adequate signal 2 for priming. Immunization of mice with nickel-binding proteins pretreated with Ni(IV), but not with Ni(II), allowed them to generate nickel-specific CD4+ T cell hybridomas. Ni(II) sufficed for restimulation of T cell hybridomas; in this and other aspects as well, the hybridomas resembled the nickel-specific human T cell clones reported in the literature. Interestingly, restimulation of hybridomas did not require the original Ni(IV)-protein complex used for priming, suggesting either that the nickel ions underwent ligand exchange toward unknown self proteins or peptides or that nickel recognition by the TCR is carrier-independent. In conclusion, we found that Ni(III) and Ni(IV), but not Ni(II) alone, were able to sensitize naive T cells. Since both Ni(III) and Ni(IV) can be generated from Ni(II) by reactive oxygen species, released during inflammation, our findings might explain why in humans nickel contact dermatitis develops much more readily in irritated than in normal skin.
Peptide Dose, Affinity, and Time of Differentiation Can Contribute to the Th1/Th2 Cytokine Balance
Authors: Rogers Paul R. , Croft Michael
Published: December 2022

Opposing viewpoints exist regarding how Ag dose and affinity modulate Th1/Th2 differentiation, with data suggesting that both high and low level stimulation favors Th2 responses. With transgenic T cells bearing a single TCR, we present novel data, using peptides differing in affinity for the TCR, that show that the time period of differentiation can determine whether Th1 or Th2 responses predominate as the level of initial stimulation is altered. Over the short term, IFN-γ-producing cells were induced by lower levels of stimulation than IL-4-producing cells, although optimal induction of both was seen with the same high level of stimulation. Over the long term, however, high doses of high affinity peptides led selectively to IFN-γ-secreting cells, whereas IL-4- and IL-5-secreting cells predominated with lower levels of initial signaling, brought about by moderate doses of high affinity peptides. In contrast, too low a level of stimulation at the naive T cell stage, with low affinity peptides at any concentration, promoted only IL-2-secreting effectors or was not sufficient for long term T cell survival. These results demonstrate that the level of signaling achieved through the TCR is intimately associated with the induction of distinct cytokine-secreting T cells. We show that dose, affinity, time over which differentiation occurs, and initial production of IL-4 and IFN-γ all can contribute to which T cell subset will predominate. Furthermore, these data reconcile the two opposing views on the effects of dose and affinity and provide a unifying model of Th1/Th2 differentiation based on strength of signaling and length of response.
Intranasal Exposure to Protein Antigen Induces Immunological Tolerance Mediated by Functionally Disabled CD4+ T Cells
Authors: Tsitoura Daphne C. , DeKruyff Rosemarie H. , Lamb Jonathan R. , Umetsu Dale T.
Published: December 2022

In this study we examined the immunological parameters underlying the natural immunity to inhaled nonpathogenic proteins. We addressed this question by examining the effect of intranasal exposure to OVA in both wild-type mice and mice reconstituted with OVA-TCR transgenic CD4+ T cells. Intranasal administration of OVA induced an initial phase of activation during which CD4+ T cells were capable of proliferating and producing cytokines. Although many of the OVA-specific CD4+ T cells were subsequently depleted from the lymphoid organs, a stable population of such T cells survived but remained refractory to antigenic rechallenge. The unresponsive state was not associated with immune deviation due to selective secretion of Th1- or Th2-type cytokines, and the presence of regulatory CD8+ T cells was not required. Moreover, neutralization of the immunosuppressive cytokines IL-10 and TGF-β did not abrogate the induction of tolerance. Inhibition of the interaction of T cells with CD86, but not CD80, at the time of exposure to intranasal Ag prevented the development of unresponsiveness, while selective blockade of CTLA-4 had no effect. Our results suggest that intranasal exposure to Ags results in immunological tolerance mediated by functionally impaired CD4+ T cells via a costimulatory pathway that requires CD86.
T Cell Development in PU.1-Deficient Mice
Authors: Spain Lisa M. , Guerriero Anastasia , Kunjibettu Sudeesha , Scott Edward W.
Published: December 2022

These studies address the role of PU.1 in T cell development through the analysis of PU.1−/− mice. We show that the majority of PU.1−/− thymocytes are blocked in differentiation prior to T cell commitment, and contain a population of thymocyte progenitors with the cell surface phenotype of CD44+, HSAbright, c-kitint, Thy-1−, CD25−, Sca-1−, CD4−, and CD8−. These cells correspond in both number and cell surface phenotype with uncommitted thymocyte progenitors found in wild-type fetal thymus. RT-PCR analysis demonstrated that PU.1 is normally expressed in this early progenitor population, but is down-regulated during T cell commitment. Rare PU.1−/− thymi, however, contained small numbers of thymocytes expressing markers of T cell commitment. Furthermore, almost 40% of PU.1−/− thymi placed in fetal thymic organ culture are capable of T cell development. Mature PU.1−/− thymocytes generated during organ culture proliferated and produced IL-2 in response to stimulation through the TCR. These data demonstrate that PU.1 is not absolutely required for T cell development, but does play a role in efficient commitment and/or early differentiation of most T progenitors.
Recombinant IFN-α (2b) Increases the Expression of Apoptosis Receptor CD95 and Chemokine Receptors CCR1 and CCR3 in Monocytoid Cells
Authors: Zella Davide , Barabitskaja Oxana , Casareto Luca , Romerio Fabio , Secchiero Paola , Reitz Marvin S. , Gallo Robert C. , Weichold Frank F.
Published: December 2022

IFN-α-2b, known as potent immune modulator, can either inhibit or enhance immune cell activity within the tightly regulated microenvironment of inflammation, depending upon the concentration of the cytokine and the activation stage of the cell. Chemokine receptors, which not only mediate chemotaxis of immune cells to the site of inflammation but also affect cellular activation by transferring corresponding signals, represent yet another level of immune regulation. Here we demonstrate that IFN-α increases the expression of CCR1 and CCR3 in primary mononuclear phagocytes, as well as in the monocytoid cell line U937. Enhanced receptor mRNA expression correlated with functional readouts such as increased intracellular calcium mobilization and cell migration in response to ligands. Expression of CCR2b, CCR4, CCR5, and CXCR4 was unchanged or decreased after IFN-α treatment. These observations indicate a differentially regulated cellular signaling relationship of IFN-α pathways and chemokine receptor expression. We also provide evidence that, under these conditions, IFN-α treatment increased the expression of CD95 (Fas, Apo1), resulting in enhanced susceptibility to apoptosis. Taken together, these data add important information for the rational application of IFN-α (2b) in immune and cancer therapies.
A Role for IL-16 in the Cross-Talk Between Dendritic Cells and T Cells
Authors: Kaser Arthur , Dunzendorfer Stefan , Offner Felix A. , Ryan Thomas , Schwabegger Anton , Cruikshank William W. , Wiedermann Christian J. , Tilg Herbert
Published: December 2022

Dendritic cells (DCs) in the periphery capture and process Ags, migrate to lymphoid organs, and initiate immune responses in T cells. IL-16, the soluble ligand for CD4, is a potent chemoattractant for CD4+ T cells, eosinophils, and monocytes and is mainly derived from activated T cells. Because migration is a fundamental property of DCs, we asked whether IL-16 induces chemotaxis in DCs and whether DCs are a source of IL-16. DCs were generated by culture of monocytes in IL-4 and GM-CSF for 6 days and subsequently highly purified employing magnetic beads. Migration was assayed by nitrocellulose and polycarbonate filter-based assays, and distinction of chemotaxis and chemokinesis was performed by a checkerboard analysis. Messenger RNA and protein data revealed constitutive expression and release of IL-16 by day-6 DCs. Gradients of rIL-16 induced a chemotactic response of DCs. Furthermore, the chemotactic activity of DC supernatant toward DCs themselves and T cells was mainly due to IL-16, because the addition of neutralizing Abs completely abrogated the migratory response. However, after induction of maturation by the addition of TNF-α and PGE2 DCs, neither expressed IL-16 mRNA nor produced IL-16 protein. We conclude that IL-16 may play a role in the trafficking of DCs and may be a major chemotactic signal from DCs toward themselves and toward T cells.
Cell Surface Expression of the Endoplasmic Reticular Heat Shock Protein gp96 Is Phylogenetically Conserved
Authors: Robert Jacques , Ménoret Antoine , Cohen Nicholas
Published: December 2022

In mammals, the heat shock protein gp96 complexed to antigenic peptides elicits T cell adaptive immunity. By itself, however, gp96 can evoke responses that are characteristic of innate immunity. Interestingly, this protein, which resides in the endoplasmic reticulum, is expressed on the surface of certain mouse tumor cells. Given that heat shock proteins are highly conserved, we investigated whether the cell surface expression of gp96 is also evolutionarily conserved. Our data reveal that gp96, most likely containing the endoplasmic reticulum retention motif (KDEL), is expressed on the surface of three different Xenopus lymphoid tumor cell lines, each derived from a different spontaneously arising thymic tumor. Levels of expression differ among the tumor lines tested, with more immunogenic tumors expressing greater amounts of surface gp96. Moreover, a high level of gp96 surface expression is detectable on a subset of Xenopus normal nontransformed splenic lymphocytes (mainly surface IgM+ B cells) but not on other normal cells, including macrophages and nucleated erythrocytes. Surface expression of a gp96 protein homologue occurs also on some, but not all, T and B cell clones derived from peripheral blood cells of the channel catfish, as well as on lymphocyte-like cells, but not on erythrocytes from the hagfish, a primitive agnathan vertebrate lacking markers of an adaptive immune system. gp96 is actively directed to and retained on the plasma membrane of Xenopus lymphocytes and tumor cells and hagfish lymphocyte-like cells by a process that requires vesicular transport. This selective surface expression of gp96 on some immune cells from different vertebrate classes is consistent with an ancestral immunological role of gp96 as danger-signaling molecule.
VIP and PACAP Differentially Regulate the Costimulatory Activity of Resting and Activated Macrophages Through the Modulation of B7.1 and B7.2 Expression
Authors: Delgado Mario , Sun Wei , Leceta Javier , Ganea Doina
Published: December 2022

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP), two structurally related neuropeptides produced and/or released within the lymphoid microenvironment, modulate numerous immune functions. Although primarily antiinflammatory in nature, VIP and PACAP also affect resting macrophages. In this study, we report on in vitro and in vivo dual effects of VIP/PACAP on the expression of B7.1 and B7.2 and on the costimulatory activity for T cells in unstimulated and LPS/IFN-γ-activated macrophages. VIP and PACAP up-regulate B7.2, but not B7.1, expression and induce the capacity to stimulate the proliferation of naive T cells in response to soluble anti-CD3 or allogeneic stimulation. In contrast, both neuropeptides down-regulate B7.1/B7.2 expression on LPS/IFN-γ-activated macrophages and inhibit the endotoxin-induced costimulatory activity for T cells. Interestingly, both the stimulatory and the inhibitory effects of VIP/PACAP are mediated through the specific receptor VPAC1 and involve the cAMP/protein kinase A transduction pathway. The dual effect on B7.1 and B7.2 expression occurs at both mRNA and protein level and correlates with the VIP/PACAP regulation of the macrophage costimulatory activity. Through their regulatory role for resting and activated macrophages, VIP and PACAP act as endogenous participants in the control of immune homeostasis. Their effects depend not only on the timing of their release, but also on the activation and differentiation state of the neighboring immune cells.
Monoclonal Antibodies That Distinguish Between Two Related Digitalis Glycosides, Ouabain and Digoxin
Authors: Parhami-Seren Behnaz , Bell Charles , Margolies Michael N. , Haupert Garner T.
Published: December 2022

The exogenous digitalis glycosides, ouabain and digoxin, have been widely used in humans to treat congestive heart failure and cardiac arrhythmias. Several reports have also pointed to the existence of endogenous ouabain- and digoxin-like compounds, but their precise roles in mammalian physiology and various disorders of the circulation are not clear. In an attempt to produce specific Abs for the purification and identification of endogenous ouabain-like compounds, somatic cell fusion was used to produce mAbs specific for ouabain. Our attempts to produce ouabain-specific mAbs were unsuccessful when ouabain was coupled to exogenous proteins such as bovine γ-globulins, BSA, and human serum albumin. However, when ouabain was coupled to an Ab of A/J mice origin and the same strain of mouse was used for immunization with ouabain-Ab conjugate, three Abs (1-10, 5A12, and 7-1) specific for ouabain were obtained. In assays of fluorescence quenching and saturation equilibrium with tritiated ouabain, Ab 1-10 exhibited 200 nM affinity for ouabain. These three mAbs are distinguished from existing Abs to ouabain and digoxin by their specificity for ouabain and lack of cross-reactivity with digoxin. Specificity studies showed that the loss of cross-reactivity was correlated with the presence of a hydroxyl group at either position 12β (digoxin) or 16β (gitoxin) of the steroid ring. These Abs can be used to develop assays for detection and characterization of ouabain-like molecules in vivo.
Mitochondria Connects the Antigen Receptor to Effector Caspases During B Cell Receptor-Induced Apoptosis in Normal Human B Cells
Authors: Berard Marion , Mondière Paul , Casamayor-Pallejà Montserrat , Hennino Ana , Bella Chantal , Defrance Thierry
Published: December 2022

We have previously reported that CD40 stimulation sensitizes human memory B cells to undergo apoptosis upon subsequent B cell receptor (BCR) ligation. We have proposed that activation stimuli connect the BCR to an apoptotic pathway in mature B cells and that BCR-induced apoptosis of activated B cells could serve a similar function as activation-induced cell death in the mature T cell compartment. Although it has been reported that caspases are activated during this process, the early molecular events that link the Ag receptor to these apoptosis effectors are largely unknown. In this study, we report that acquisition of susceptibility to BCR-induced apoptosis requires entry of memory B cells into the S phase of the cell cycle. We also show that transduction of the death signal via the BCR sequentially proceeds through a caspase-independent and a caspase-dependent phase, which take place upstream and downstream of the mitochondria, respectively. Furthermore, our data indicate that the BCR-induced alterations of the mitochondrial functions are involved in activation of the caspase cascade. We have found both caspases-3 and -9, but not caspase-8, to be involved in the BCR apoptotic pathway, thus supporting the notion that initiation of the caspase cascade could be under the control of the caspase-9/Apaf-1/cytochrome c multimolecular complex. Altogether, our findings establish the mitochondria as the connection point through which the Ag receptor can trigger the executioners of apoptotic cell death in mature B lymphocytes.
Natural Killing of Xenogeneic Cells Mediated by the Mouse Ly-49D Receptor
Authors: Nakamura Mary C. , Naper Christian , Niemi Eréne C. , Spusta Steven C. , Rolstad Bent , Butcher Geoffrey W. , Seaman William E. , Ryan James C.
Published: December 2022

NK lymphocytes lyse certain xenogeneic cells without prior sensitization. The receptors by which NK cells recognize xenogeneic targets are largely uncharacterized but have been postulated to possess broad specificity against ubiquitous target ligands. However, previous studies suggest that mouse NK cells recognize xenogeneic targets in a strain-specific manner, implicating finely tuned, complex receptor systems in NK xenorecognition. We speculated that mouse Ly-49D, an activating NK receptor for the MHC I ligand, H2-Dd, might display public specificities for xenogeneic target structures. To test this hypothesis, we examined the lysis of xenogeneic targets by mouse Ly-49D transfectants of the rat NK cell line RNK-16 (RNK.Ly-49D). Of the xenogeneic tumor targets tested, RNK.Ly-49D, but not untransfected RNK-16, preferentially lysed tumor cells derived from Chinese hamsters and lymphoblast targets from rats. Ly-49D-dependent recognition of Chinese hamster cells was independent of target N-linked glycosylation. Mouse Ly-49D also specifically stimulated the natural killing of lymphoblast targets derived from wild-type and MHC-congenic rats of the RT1lv1 and RT1l haplotypes, but not of the RT1c, RT1u, RT1av1, or RT1n haplotypes. These studies demonstrate that Ly-49D can specifically mediate cytotoxicity against xenogeneic cells, and they suggest that Ly-49D may recognize xenogeneic MHC-encoded ligands.
p38 Mitogen-Activated Protein Kinase Regulates Human T Cell IL-5 Synthesis
Authors: Mori Akio , Kaminuma Osamu , Miyazawa Keiji , Ogawa Koji , Okudaira Hirokazu , Akiyama Kazuo
Published: December 2022

Involvement of p38 mitogen-activated protein (MAP) kinase in human T cell cytokine synthesis was investigated. p38 MAP kinase was clearly induced in human Th cells activated through the TCR. SB203580, a highly selective inhibitor of p38 MAP kinase, inhibited the induction of p38 MAP kinase in human Th cells. Major T cell cytokines, IL-2, IL-4, IL-5, and IFN-γ, were produced by Der f 2-specific Th clones upon stimulation through the TCR. IL-5 synthesis alone was significantly inhibited by SB203580 in a dose-dependent manner, whereas the production of IL-2, IL-4, and IFN-γ was not affected. The proliferation of activated T cells was not affected. IL-5 synthesis of human Th clones induced upon stimulation with rIL-2, phorbol ester plus anti-CD28 mAb, and immobilized anti-CD3 mAb plus soluble anti-CD28 mAb was also suppressed by SB203580 in the same concentration response relationship. The results clearly indicated that IL-5 synthesis by human Th cells is dependent on p38 MAP kinase activity, and is regulated distinctly from IL-2, IL-4, and IFN-γ synthesis. Selective control of IL-5 synthesis will provide a novel treatment devoid of generalized immune suppression for bronchial asthma and atopic dermatitis that are characterized by eosinophilic inflammation.
CD40 Ligand Blockade Induces CD4+ T Cell Tolerance and Linked Suppression
Authors: Honey Karen , Cobbold Stephen P. , Waldmann Herman
Published: December 2022

The CD40-CD40 ligand (CD40L) interaction is a key event in the initiation of an adaptive immune response, and as such the therapeutic value of CD40L blockade has been studied in many experimental models of tissue transplantation and autoimmune disease. In rodents, transplantation of allogeneic tissues under the cover of anti-CD40L Abs has resulted in prolonged graft survival but not tolerance. In this report, we show that failure to induce tolerance probably results from the inability of anti-CD40L Abs to prevent graft rejection elicited by the CD8+ T cell subset. When the CD8+ T cell population is controlled independently, using anti-CD8 Abs, then tolerance is possible. Transplantation tolerance induced by anti-CD4 mAbs can often be associated with dominant regulation, manifested as infectious tolerance and linked suppression, both of which are mediated by CD4+ T cells. We show here that CD4+ T cells rendered tolerant using anti-CD40L therapy exhibit the same regulatory property of linked suppression, as demonstrated by their ability to accept grafts expressing third party Ags only if they are expressed in conjunction with the tolerated Ags. This observation of linked suppression reveals a hitherto undocumented consequence of CD40L blockade that suggests the tolerant state is maintained by a dominant regulatory mechanism. Our results suggest that, although anti-CD40L Abs are attractive clinical immunotherapeutic agents, additional therapies to control aggressive CD8+ T cell responses may be required.
4-1BB Ligand, a Member of the TNF Family, Is Important for the Generation of Antiviral CD8 T Cell Responses
Authors: Tan Joyce T. , Whitmire Jason K. , Ahmed Rafi , Pearson Thomas C. , Larsen Christian P.
Published: December 2022

4-1BB (CD137) is a costimulatory molecule expressed on activated T cells and interacts with 4-1BB ligand (4-1BBL) on APCs. To investigate the role of 4-1BB costimulation for the development of primary immune responses, 4-1BBL-deficient (4-1BBL−/−) mice were infected with lymphocytic choriomeningitis virus (LCMV). 4-1BBL−/− mice were able to generate CTL and eliminate acute LCMV infection with normal kinetics, but CD8 T cell expansion was 2- to 3-fold lower than in wild-type (+/+) mice. In the same mice, virus-specific CD4 Th and B cell responses were minimally affected, indicating that 4-1BB costimulation preferentially affects CD8 T cell responses. This result contrasts with our earlier work with CD40L-deficient (CD40L−/−) mice, in which the CD8 T cell response was unaffected and the CD4 T cell response was markedly impaired. When both 4-1BBL- and B7-dependent signals were absent, CD8 T cell expansion was further reduced, resulting in lower CTL activity and impairing their ability to clear LCMV. Altogether, these results indicate that T cells have distinct costimulatory requirements: optimal CD8 responses require 4-1BBL-dependent interactions, whereas CD4 responses are minimally affected by 4-1BB costimulation, but require CD40-CD40L and B7-dependent interactions.
Observations on the Standardization of Antipneumococcus Serum by the Protection Test
Authors: Odell Helen R.
Published: December 2022

It is important to record the fact that antipneumococcus sera may maintain their protective activity without appreciable evidence of deterioration for eight or more years. By the method for measuring the potency of different sera used in the foregoing tests, the ratios between the potency of the standard serum and the test sera were remarkably uniform, indicating the accuracy of the technic. Irregularities are attributed largely to variations in the susceptibility of the mice. The variation in protection, which occurred with both standard and test sera from time to time, must in general be attributed to changes in virulence of the standard culture. Dilution of the culture is not an adequate criterion when cultures of excessively exalted virulence are used.

Minor modifications, such as special attention to environmental conditions during growth of the pneumococcus and the use of more mice, which were adopted in the later years, have further increased the reliability and usefulness of the test.

As stressed in an earlier paper (11), a standard control serum is essential to the standardization of antipneumococcus serum, and it must be included in every test.
Studies on the “Toxins” of Hemolytic Streptococci
Authors: Ando K. , Nishimura H.
Published: December 2022

Summary and Conclusions

The specific toxin has been almost completely precipitated by the addition of 2 volumes of alcohol both from culture filtrate and from the broth culture itself, and easily obtained in a form of solution by simple saline extraction of this precipitate. The specific toxin is not easily dialyzable. No precipitation occurred when 2 volumes of alcohol were added to one volume of dialyzed culture filtrate, but abundant precipitate of the specific toxin was observed when in addition to alcohol a small amount of saturated salt solution was added to the dialyzed filtrate. A small portion of the specific toxin may be precipitated by acid from a culture filtrate, dialyzed filtrate and crude specific toxin (solution of alcoholic precipitate). When the alcoholic precipitate of specific toxin was dissolved in a small amount of saline solution, an insoluble part remained. The suspension and the washings from this insoluble part caused positive skin reactions on white pigs, while the washings from an acid precipitate of the culture filtrate or crude specific toxin gave no skin reaction on the same animals even in a higher concentration. Accordingly, the acid precipitate seems to contain the specific toxin not merely by adsorption, but perhaps in a form of chemical combination, probably, with nucleoprotein.
Hypersensitiveness to Diphtheria Bacterial Products
Authors: Neill James M. , Sugg John Y. , Richardson Lurline V.
Published: December 2022

This paper reports the anaphylactic reactions of guinea pigs immunized with toxoid and subsequently injected intravenously either with phenolized filtrate containing the toxin antigen or with formolized filtrate containing the toxoid antigen. It was proved that the acute death of the antitoxic immune animals represented true anaphylactic reactions specific to bacterial products contained in diphtheria filtrate.

While it was recognized that other constituents participate to some extent, the evidence as a whole indicated that the toxin or toxoid antigen is the principal agent of the anaphylactic reaction of antitoxic immune guinea pigs to unheated filtrates containing a relatively large proportion of toxin or toxoid. The complications due to the substances other than toxin or toxoid are least prominent if one uses both for the immunization and for the intravenous test, minimal amounts of unheated filtrate in which toxoid is the dominant antigen, and finally selects for intravenous test the individual guinea pigs that had been “earliest” in antitoxin production. As might be expected, the complications become more prominent if either the immunization or the intravenous anaphylaxis test is made with diphtheria filtrate in which toxin or toxoid is not the dominant antigen (e.g., filtrates of weakly toxicogenic strains or heated filtrates of toxicogenic strains).

Most of the experiments were made with toxoid-immunized guinea pigs, but after a proper rest period animals immunized with toxin-antitoxin gave anaphylactic reactions to intravenous injection of formolized toxoid-containing filtrates.
Could mid-upper arm circumference be a valid proxy to the body mass index for elderly persons?
Authors: Goswami Anil Kumar , Sathiyamoorthy Ramadass , Mani Kalaivani , Kant Shashi , Gupta Sanjeev Kumar
Published: December 2022

Introduction:

In elderly persons, due to physiological, anatomical, and functional changes, body mass index (BMI) may not be suitable for the assessment of nutritional status. Mid-upper arm circumference (MUAC) can be a proxy indicator to identify underweight and overweight/obesity among elderly persons. This study aimed to estimate the correlation between MUAC and BMI, and the cutoffs for MUAC using receiver operating characteristic (ROC) analysis.

Material and Methods:

This survey was carried out in a resettlement colony of Delhi. The participants were residents of the area who were aged 60 years or older, and selected by a simple random sampling technique. The arm span, weight, and MUAC of the participants were measured. The correlation between MUAC and BMI for gender and age group was calculated. The ROC curve was also constructed.

Results:

A total of 946 eligible participants were enrolled. The correlation between MUAC and BMI was 0.67 (P < 0.001) and 0.76 (P < 0.001) among men and women, respectively. The MUAC cutoff for underweight was <25 cm with a sensitivity of 68.8% and specificity of 84.9%. The area under the curve (AUC) was 0.84 (0.80–0.88). The MUAC cutoff for overweight/obesity was ≥27 cm with a sensitivity of 83.9% and specificity of 64.9%, and AUC was 0.78 (0.75–0.82).

Conclusion:

The MUAC of the participants increased as the BMI of the participants increased. MUAC cutoff was determined using the ROC curve for underweight and overweight/obesity among elderly persons.
Assessment of sleep quality among postgraduate residents of a tertiary care hospital in Kashmir
Authors: Yousuf Awhad Mueed , Qazi Tanzeela Bashir
Published: December 2022

Introduction:

The Postgraduate medical training is long and emotionally taxing. These occupations are associated with stress and good workload along with night shifts which effects the sleep quality. Studies have documented that high levels of stress among medical residents have been associated with sleep problems. Our study aims to investigate sleep quality among the postgraduate residents of a tertiary care hospital using Pittsburgh Sleep Quality Index.

Material and Methods:

It was a cross sectional study that was conducted from 1 November 2021 to 31 December 2021. Study participants included Postgraduate medical residents working at a tertiary care hospital in district Srinagar of Kashmir valley. A total of 400 participants took part in the study.

Results:

The mean age of the participants was 33.4 years (S.D 4.9). Majority of the participants (54%) were females. The mean global Pittsburgh Sleep Quality Index score (±SD) for sleep quality was 8.46 (±4.5) with a median score of 6 and Inter Quartile Range of 6.5.

Conclusion:

Poor sleep quality was reported in 75% of the residents. This highlights the need for awareness about this problem. There is a need for early interventions in order to introduce flexible working hours for medical residents and to provide shifts of manageable durations.
Utilization of modern family planning methods among women of reproductive age group in North-Central Nigeria; rural – urban comparison
Authors: Hassan Ikrama , Lucky Changkat , Michael Anazodo , Caleb Odonye Eselema , Hellen Kwakipi , Adaku Ezeala , Ahmed Lawal Abdulmumuni , Ezekiel Tomen , Anna Joshua , Oyeleke Bello Surajudeen
Published: December 2022

Introduction:

Contraception is one of the most successful developmental interventions, unique in women empowerment and population control. Family planning (FP) reinforces the right to determining the number and spacing of children. Hence, we determine the utilization of modern FP methods among urban and rural dwellers.

Material and Methods:

This is a cross-sectional study of reproductive age women in Lafia, Nigeria. Ten primary healthcare centers (PHCs) each were selected from the urban and rural locations over 6 months using multi-staged sampling technique. Questionnaire was administered, and the data were analyzed using SPSS V 23. P < 0.05 was considered significant.

Results:

Most participants were aged between 20 and 29 years. The prevalence of using modern methods of FP was 17.3%. More than three quarters of urban women are using contraceptives compared with one quarter of rural women. There was a difference between those who ever used measures to delay pregnancy and their locations, P = 0.049. Women in the rural areas use the cycle beads, while those in the urban areas use the injectables. Need for more children was the most common reason for discontinuing FP, others are FP failure, absence of spouse, and fear of side effects. Age of the participants was found to be a good predictor of using modern FP method, P = 0.022.

Conclusion:

There is low prevalence of modern FP utilization in this study despite knowing where to access the services (PHCs). Three of four urban women are using FP compared with one out of four among rural women. The cycle beads and the injectables were the most common methods. Age is a major determinant of using FP.
Morbidity profile and dynamics of determinants of health-seeking behaviour in geriatric population of Chandigarh, India
Authors: Puri Sonia , Bhandari Praizy , Goel N. K. , Sharma Munish Kumar , Lehl Sarabmeet Singh , Gupta Monica
Published: December 2022

Introduction:

Aging is a natural process that usually results in physiological, biological, emotional, and financial decline. As a result, a robust health system is required to meet their escalating health needs. Through this study, we got an opportunity to study the morbidity profile of the elderly and to assess their health-seeking behavior and its determinants in urban areas of Chandigarh.

Material and Methods:

The sample consisted of 360 participants. Multistage and proportionate sampling techniques were used to recruit study subjects. A structured interview was carried out to get information on the different parameters of health-seeking behavior of the elderly population.

Results:

The most pervasive determinant of health-seeking behavior was perceiving health issues related to age, no family support, and health-care expenditure.

Conclusion:

The elderly had a positive behavior toward seeking help with regard to health care. Multiple morbidities were evident among the elderly, and modern medication was the greatest choice. Improved perspective toward health, easy accessibility, and awareness regarding the disease may contribute to the willingness of seeking help for the health-care needs.
Health-related quality of life
Authors: Singh Pallika , Rasania S. K.
Published: December 2022

Quality of life (QoL) is a multidimensional concept and an essential health component that usually includes both positive and negative aspects of life. The measure of health-related QoL (HRQOL) enables health agencies and social partners to address areas of public health importance and formulate policies which eventually demonstrate the impact of health on QoL. Women form an important pillar of society as they are the primary caretaker of children and elders in every country of the world and therefore, the QoL of women determines the health of the next generation and future public health challenges for families, communities, and the health-care system. Providing health services at par with quality is the need of the hour and a very important health goal considering women's health. Poor delivery of clinical care, failure to meet the professional standards of patient care by health-care providers, mistreatment and abuse by health-care professionals, and inequitable delivery of care are some of the key issues in the delivery of quality maternal health-care services in India and therefore primary health-care professionals should be made familiar with the concept of the HRQoL in the community they are serving. Indian health-care systems need to address to the inequalities and taking off the consumer-centric, market approach of privately run corporate health facilities along with setting up of accountability of all the stakeholders to provide quality care, especially in the government-run facilities and creating a promising environment in health care for women focusing on pregnant and postpartum mothers.
Efficacy of Modified Ventilator-Associated Pneumonia Prevention Bundles on Ventilator-Associated Pneumonia Incidence Rate in the Intensive Care Unit
Authors: Yuvaraj A.
Published: December 2022

Ventilator-associated pneumonia (VAP) is defined as pneumonia that develops in an intubated patient after 48 h of mechanical ventilation. In India, there is a paucity of literature in terms of compliance to VAP prevention bundles and their benefits. The aim of this study was to compare the reduction of VAP incidence rates amongst patients who received existing VAP prevention bundles and modified VAP prevention bundles. This pilot study was conducted in the adult intensive care unit of a tertiary care hospital. There were 60 patients in all, 30 patients in each group. The diagnosis of VAP was based on the clinical presentation and correlation with Clinical Pulmonary Infection Score. The incidence of VAP was 3/435 ventilator days (6.80%) in the patients receiving a modified VAP prevention bundle. In the conventional VAP prevention bundle group, the incidence of VAP was six episodes per 439 ventilator days (13.60%). Our study concluded that the modified VAP prevention bundle is effective in reducing the incidence of VAP amongst intubated patients.
Cornual Pregnancy
Authors: Dorathy Irene
Published: December 2022

Ectopic pregnancy is one of the major causes of maternal morbidity and mortality. Most ectopic pregnancies are diagnosed very late when mothers present with symptoms of rupture, and it can be fatal. Cornual pregnancy is a rare type of ectopic pregnancy where the gestational sac is implanted in the cornua of the uterus. It is more dangerous than other ectopic pregnancies, contributing to significant maternal mortality and morbidity. It is most often misdiagnosed or diagnosed late. Here is a case report of a patient who presented with recurrent cornual pregnancy and was managed appropriately and effectively at a tertiary hospital.
An observational study on health-related quality of life and persistent symptoms in COVID-19 patients after hospitalization at a tertiary care centre
Authors: Shah Chirali , Keerthi B. Y , Gali Jayasri Helen
Published: December 2022

Aim:

The study aims to determine persistent symptoms and effects of COVID-19 infection on the quality of life (QOL) at 1 and 3 months after the acute phase of the disease in mild, moderate and severe cases.

Methods:

The prospective observational study was conducted among patients with confirmed COVID-19 who had been treated and discharged after hospitalization from February 2021 to June 2021. All patients were interviewed at 1 and 3 months post discharge to assess persisting symptoms and health-related QOL. QOL was assessed using European Quality Of Life 5-Dimensions 3-Levels (EQ-5D-3L) and EuroQol-visual analogue scales (EQ-VAS).

Results:

In total, 388 out of 479 discharged following COVID-19 infection were included. The median age of patients was 48 years, with 62.6% male predominance. Most of the COVID-19 cases were mild (67.01%). Most common presenting symptom was fever (69.8%). EQ-5D-3L showed that the problems reported at 3-month follow-up were significantly less when compared to 1-month follow-up (p < 0.001), and QOL significantly improved after 3 months in non-intensive care unit (ICU) patients when compared to ICU patients (p = 0.007). The mean EQ-VAS score significantly improved at 3 months when compared to 1 month (80.34 ± 12.77 vs. 91.69 ± 12.34; P < 0.001). The severity of illness was correlated with QOL (p < 0.007).

Conclusion:

The study results demonstrate ongoing improvement in the QOL and persistent symptoms, while a minority still were symptomatic after 3 months post-COVID-19 illness.
Navigating patient journey in early diagnosis of lung cancer in India
Authors: Biswas Bivas , Talwar Deepak , Meshram Priti , Julka Pramod K. , Mehta Anurag , Somashekhar SP , Chilukuri Srinivas , Bansal Abhishek
Published: December 2022

Lung cancer (LC) is one of the leading causes of cancer deaths worldwide. In India, the incidence of LC is increasing rapidly, and a majority of the patients are diagnosed at advanced stages of the disease when treatment is less likely to be effective. Recent therapeutic developments have significantly improved survival outcomes in patients with LC. Prompt specialist referral remains critical for early diagnosis for improved patient survival. In the Indian scenario, distinguishing LC from benign and endemic medical conditions such as tuberculosis can pose a challenge. Hence, awareness regarding the red flags—signs and symptoms that warrant further investigations and referral—is vital. This review is an effort toward encouraging general physicians to maintain a high index of clinical suspicion for those at risk of developing LC and assisting them in refering patients with concerning symptoms to specialists or multidisciplinary teams as early as possible.
Prevalence of pre-extensively drug-resistant tuberculosis (Pre XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) among extra pulmonary (EP) multidrug resistant tuberculosis (MDR-TB) at a tertiary care center in Mumbai in pre Bedaquiline (BDQ) era
Authors: Utpat Ketaki V. , Rajpurohit Rakesh , Desai Unnati
Published: December 2022

Background:

Drug-resistant tuberculosis (DR-TB) is the most exigent and calamitous challenge encountered in treatment of TB. Extra pulmonary (EP) DR-TB poses a complex diagnostic and therapeutic challenge owing to myriad of presentations and paucibacillary nature. Data available on this subset is limited. We studied the prevalence of EPDR-TB cases among the total DR-TB cases visiting our Programmatic management of Drug-Resistant TB (PMDT) site. We also studied the demographic and microbiological profile of these cases and analyzed the prevalence of pre-extensively drug-resistant TB (pre XDR-TB) and extensively drug-resistant TB (XDR-TB) among patients of EPDR-TB in pre Bdq era.

Results:

Of the 1086 DR-TB patients, 64 (5.89%) were cases of EPDR-TB. Seven out of 64 (10.93%) were primary EPDR-TB. The site wise distribution of cases was 34 (53.125%) lymph node DR-TB, 18 (28.125%) pleural DR-TB, 9 (14.0625%) spinal DR-TB/paraspinal abscess/psoas abscess, 1 case (1.5625%) each of abdominal DR-TB, sternal and gluteal abscess. On the basis of the second-line drug susceptibility testing (DST), patients were grouped into: (1) multidrug-resistant TB (MDR-TB), (2) MDR-TB with fluoroquinolone (FQ) resistance {pre XDR XDR-TB (FQ)}, (3) MDR-TB with second-line injectable (SLI) resistance {pre XDR XDR-TB (SLI)}, (4) XDR-TB. Of the 64 patients, 43 (67.185%) had MDR-TB, 19 (29.687%) had preXDR-TB (FQ), none had preXDR-TB (SLI) and 2 (3.125%) had XDR-TB. Gastro esophageal reflux disease (GERD) was the most common comorbidity seen in 26 (40.6%) patients, followed by anemia in 5 (7.8%), psychiatry problems 5 (7.8%), hypertension in 3 (4.6%), renal disorders in 2 (3.1%) while thyroid disorder, HIV and thalassemia in 1 each (1.5%).

Conclusion:

EPDR-TB forms a small but significant proportion of total DR-TB. Lymph node DR-TB is its most common subclass. Our study emphasises the momentousness and essentiality of baseline DST to FQ and SLI in patients of DR-TB. This enables an appropriate modification of therapy at baseline itself to better the treatment outcomes.

We observed a strikingly high proportion of preXDR-TB (FQ) in our study group.
Biomarkers in severe asthma
Authors: Gvalani Aanchal , Athavale Amita , Gupta Disha
Published: December 2022

Asthma is a chronic condition of bronchial hyper-reactivity associated with inflammation ranges from mild to severe form. It affects 1 – 18% of the population globally and it is estimated that > 300million people in the world have asthma. Of this 5 – 10% have severe asthma. while the proportion of patients suffering from severe are smaller, the morbidity and mortality are higher in this group. With the advances in our understanding of the pathophysiology of asthma there is a need to understand the role of various biomarkers. We live in an era of precision medicine and today there is a clear unmet need to understand targeted therapies. This review aims to raise awareness to the available biomarkers used in clinical practice in India and their role in predicting response to targeted therapies.