Virus infection and apoptosis (issue II) an introduction: cheating death or death as a fact of life?

Apoptosis represents the cell's innate ability to self-destruct and is an important cellular response mechanism against virus infection. The purpose of this series of articles is to critically review significant advances in important areas of virology with respect to virus infection and its relationship with apoptosis. In the Introduction to the first issue (Intern. Rev. Imm., 22: 321-326, 2003), we dedicated these entire two issues to the memory of Dr. Lois K. Miller. Dr. Miller's Ph.D. advisor, Robert D. Wells, and two of her students, Rollie Clem and Lorena Passarelli, contributed touching remembrances of their associations with Dr. Miller. In the Introduction to this issue, an overview of key points of discussion detailed in each chapter of the two issues is provided. The future of the emerging field of viral apoptosis remains bright, indeed.     

A randomized trial of vitamin D supplementation to prevent seasonal influenza and enterovirus infection in children

PurposeThis study aimed to evaluate whether vitamin D supplementation can reduce the incidence of influenza and enterovirus infection in Taiwanese children.MethodsThis randomized, double-blind, controlled trial included children aged two to five years between April 2018 and October 2019 from daycare centers. All the participants were randomly assigned to a vitamin D supplementation group (2000 IU/day) or placebo group for one month. The primary outcome was the incidence of influenza and enterovirus infection in the following six months, and the secondary outcome was the incidence of influenza and enterovirus infection in the children's household members.ResultsTwo hundred and forty-eight children participated. The vitamin D group showed a relative risk reduction of 84% against influenza compared to the placebo group but did not reach statistical significance. Kaplan–Meier curves revealed that the placebo group had a higher probability of influenza infection than the vitamin D group (log-rank test, p = 0.055), but the incidence of enterovirus infection was similar between the two groups (p = 0.946) among children. Among children's household members, the incidence of influenza (p = 0.586) and enterovirus infection (p = 0.528) were both similar between the two groups. All children who were tested for serum 25(OH)D levels after vitamin D intervention had 25(OH)D levels above 30 ng/mlConclusionVitamin D supplementation may have a small preventative effect against influenza infection but does not affect enterovirus infection among preschool children. A high-dose short-term vitamin D intervention might be a way to elevate children's serum vitamin D levels in the first month of starting kindergarten.     

S. O. Lilienfeld and N. G. Waller, “A great pioneer of clinical science remembered: Introduction to the special issue in honor of Paul E. Meehl”. Journal of Clinical Psychology 61(10) 2005, 1201–1207

Originally published in J Clin Psychol 61: 1201–1207, 2005 Through an oversight on the part of Special Issue Co‐Editor Scott O. Lilienfeld, Dr. Joel Weinberger was not listed as a co‐author of the article “In Praise of Clinical Judgment: Meehl's Forgotten Legacy,” in the Introduction (p. 1205) to the Journal of Clinical Psychology Special Issue in Honor of Paul E. Meehl (Vol. 61, Issue 10, October, 2005). The Introduction should have noted that this article was co‐authored by Drs. Drew Westen and Joel Weinberger. Dr. Lilienfeld sincerely apologizes for the error.     

Awareness of cytomegalovirus infection among pregnant women in France

BackgroundCytomegalovirus (CMV) is the most frequent cause of congenital virus infection. Approximately 1% of newborns are infected by CMV at birth with severe consequences among 10% of them. Efficacy of hygienic counselling is nowadays established and should be spread.ObjectiveTo evaluate pregnant women's awareness of cytomegalovirus infection in France.Study designPregnant women receiving prenatal care, at any moment of their pregnancy, in two different obstetrics clinics with different information policies, were asked to complete a written questionnaire about CMV infection.ResultsMore than half (217/362, 60%) of the pregnant women had heard of congenital CMV infection, and most of them (72%) knew the hygiene measures to use to prevent infection. Nevertheless, most could not correctly identify the symptoms associated with congenital CMV disease. Awareness was associated with hospital's policy concerning CMV infection information, the mother's educational level, parity, and employment in health care. Indeed, when information is supposed to be given (hospital A), 74% (vs 34%) know congenital CMV infection and among them the knowledge is more precise.ConclusionsThis study tends to confirm that there is a large gap between knowledge of CMV and the burden of this disease. To bridge this gap, women should receive education about congenital CMV. Hospital-based prenatal education increases awareness and knowledge about CMV and CMV prevention.     

The Anatomical Record continues to replace wonder with knowledge through first-hand experience of acupuncture

A group of original papers is assembled for this thematic-papers issue on traditional Chinese medicine (TCM). The idea for a thematic-papers issue came from Associate Editor and Guest Editor, Jicheng Li. Jicheng's idea was to introduce concepts and studies of TCM to the editorial board of The Anatomical Record and the Journal's readership. Thus, nine papers are published that deal with biomarkers, animal models, or treatments of TCM syndromes. Uniquely, Jicheng's effort culminated in acupuncture treatment of the editorial board members by a licensed physician of TCM. We learned, first-hand by Dr. Weixue Wang, about this ancient and vibrant holistic philosophy and medical practice. Our pleasure is to share the topic and our experience with you.     

The use of coroner's autopsy reports to validate the use of targeted swabbing rather than tissue collection for rapid confirmation of virological causes of sudden death in the community

Background and objectivesIn this study, coroner's autopsy reports were used to validate results obtained from respiratory virus screening of swabs rather than tissue collected during autopsy in cases of adult death of unknown cause.Study designCoroner's autopsy samples collected for respiratory virus screening between October 2010 and February 2011, were identified. Autopsy reports were requested from cases positive for a virus. Each report was reviewed to correlate findings at autopsy with the virology result and to determine whether the virus found was listed as a contributing factor in the death.ResultsSixty-four coroner's autopsy cases were identified and a respiratory virus was found in 25 cases. Influenza A(H1N1)pdm09 virus was found most frequently, then RSV and influenza B with a dual influenza A and B infection and a parainfluenza type 1. Where multiple sites were swabbed, the virus was detected in all sites. Autopsy reports for 12 cases were obtained each reporting findings consistent with respiratory infection. Influenza A was always listed as a contributing factor in the death whereas RSV was listed once and influenza B was omitted in one case. The quality of the reports was variable and full histology was less likely to be performed in the elderly.ConclusionsWhile coroner's reports supported the use of swabbing rather than tissue collection, the lack of consistency and omission of the virology findings as contributing factors to death means that the burden of viruses on mortality statistics will remain under-estimated particularly in the elderly.     

The usefulness of TV medical dramas for teaching clinical pharmacology: A content analysis of House,M.D.

IntroductionTelevision medical dramas enjoy great popularity among the general public and university students. These dramas have been used to illustrate important aspects of medical training (doctor–patient relationships, professionalism, ethical conflicts), but their usefulness for discussing the use of drugs in medical care remains unexplored. We analyzed pharmacological issues in House, M.D. to determine their potential usefulness in teaching clinical pharmacology.Material and methodsTwo investigators, blind to each other's responses, reviewed each of the 22 episodes of the first season of House, M.D., recording the main and secondary topics dealt with as well as the drugs portrayed and rating the episode's interest for teaching clinical pharmacology (High/Medium/Low). Discordant ratings were settled by a third (or fourth, if necessary) investigator.ResultsMost episodes included information on drugs; in six, pharmacologic issues were the main topics. The episodes dealt with 115 drugs, mainly anti-infective (16.5%), cardiovascular (12.2%), CNS-acting (12.2%), and analgesic or anti-inflammatory (12.2%) drugs. Five episodes were considered very useful for teaching clinical pharmacology.DiscussionThe episodes of the first season of House, M.D. contained frequent references to drug treatment and pharmacological issues; in a few episodes, the main topic was related with clinical pharmacology. Before medical dramas are recommended as a regular teaching tool, their pedagogical efficacy should be tested empirically.     

Phosphoinositide Metabolism in Drosophila Phototransduction: A Coffee Break Discussion Leads to 30 Years of History

Abstract: The aim of this review is to summarize the history of Dr. Yoshiki Hotta and his collaborators’ contributions to the research field of Drosophila phototransduction. The electroretinogram-defective mutants reported in 1970 by Dr. Hotta and Dr. Seymour Benzer in the article entitled “Genetic dissection of the Drosophila nervous system by means of mosaics” have attracted the interest of many researchers, and have been used as a great tool to dissect the mechanisms underlying phototransduction. The early collaboration of Dr. Hotta with the group of Dr. Tohru Yoshioka, who was studying the roles of phosphoinositides in the nervous system biochemically, combined biochemical and genetic approaches to phototransduction-defective no receptor potential A (norpA) and retinal degeneration A (rdgA) mutants, which led to the hypothesis that phosphoinositide metabolism regulates phototransduction in Drosophila. This was proven later by the identification of the norpA and rdgA mutant genes, which encode phospholipase C and diacylglycerol kinase, respectively. Thus the collaboration of Dr. Hotta and Dr. Yoshioka laid the foundation of our understanding of the role of phosphoinositide metabolism in Drosophila phototransduction. In addition, a collaboration carried out with the group of Dr. Kazushige Hirosawa on the ultrastructural analyses of retinal degeneration mutants, rdgA and rdgB, led to the discovery of the subcellular membrane organelle called submicrovillar cisternae, which is involved in the phosphoinositide metabolism. In this review, the authors will summarize these results, which were inspired by Dr. Hotta's insights.     

Evidence of inability of human cytomegalovirus to reactivate Kaposi's sarcoma-associated herpesvirus from latency in body cavity-based lymphocytes

BackgroundKaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 (HHV-8)) has been determined to be the most frequent cause of malignancies in AIDS patients. It is associated primarily with Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), as well as with multicentric Castleman's disease (MCD).² The switch from the latent to the lytic stage is important in the maintenance of malignancy and viral infection. So far, the mechanism of its reactivation has not been fully understood.ObjectivesHuman cytomegalovirus (HCMV) and KSHV might infect the same cells, and it was found by other groups that several viruses could reactivate KSHV from latency. We investigate whether HCMV infection could reactivate KSHV from latency in body cavity-based lymphocyte (BCBL-1) cells.Study design and resultsLaboratory strains of HCMV cannot infect B cells. In this article, we demonstrate that the UL131-repaired HCMV (vDW215-BADrUL131) derived from AD169 strain is able to infect B lymphocytes. We directly infected KSHV latent cells including BCBL-1 with vDW215-BADrUL131 to evaluate the ability of HCMV to reactivate KSHV. Inconsistent with previous reports in human fibroblast cells, our results provide direct evidence that HCMV is unable to reactivate KSHV from latency-to-lytic infection in BCBL-1 cell lines. As a control, herpes simplex virus type 1 (HSV-1) was shown to be able to reactivate KSHV.ConclusionsOur observations, different from others, suggest that reactivation mechanisms for KSHV might vary in different cells.     

Reappraising Winnicott's The Piggle: A Critical Commentary

The Piggle is one of only two substantial psychoanalytic case histories to be published under Winnicott's name. Winnicott felt that the case and the associated notes and reflections provided important material for discussion. Claire Winnicott – his wife and literary executor – wanted to bring these to an audience, and did so by overseeing the posthumous publication of the work in 1977. The nature and purpose of the work's message is explored in an extended paper published in two parts, in this and the next issue of the Journal. In Part I, published here, the author discusses the work in its historical context alongside other contemporary child analyses (notably Klein's Narrative of a Child Analysis and McDougall's Dialogue with Sammy) and its ambivalent reception by its contemporary audience. The author identifies theoretical issues raised by the material; the use of commotional and conjunctional interpretations; the use of time, and analysis on demand; the place of play in therapy and the role of the parents. He reviews the dialogue between analyst and child as set out in the text, identifying emerging themes. He attempts to understand what the child, Gabrielle, was trying to communicate. He then reviews Winnicott's interpretation of those sessions, identifying areas in which the interpretations may be at odds with what the child was experiencing. At the end the author encourages the reader to re‐read Winnicott's original text before reading the discussion and critical evaluation that forms the basis of the second part of the paper, ‘Discussion and Critique’.     

Recovery of a cytopathogenic agent from patients with non-diphtheritic croup and from Day-Nursery children. I. Properties of the agent

Summary A microbial agent, probably viral in nature, was recovered from the throat and faeces of patients with non-diphtheritic croup and from Day-Nursery-children. The agent is cytopathogenic in human embryo lung tissue cultures and after adaptation in monkey kidney cells, but not in common laboratory hosts or embryonated eggs. The agent haemagglutinates human erythrocytes. H-I tests were possible to perform. No complement-fixation was obtained with the agent as antigen. An antigenic analysis of 19 strains showed only one serological type to be prevalent. No relation was found to Polio, Echo, Adenoviruses, CA-virus, parotitic, or Sendai virus. No relationship was found to B or C group influenza virus, but FM-1 A` showed some relation in H-I tests, although not in neutralizing tests. Other evidence is presented, suggesting the relation with influenza virus A` to be improbable.The authors are indebted to Dr.K. Jensen (Sendai), Dr.R. M. Chanock (CA-virus), Dr.L. Heller (influenza antigens, antiserum and strains), Dr.A. Svedmyr (Adenovirus and Echo virus), and Dr.W. J. Mogabgab (Strain 2060) for making available sera and/or strains.     

Assessment of hepatitis B surface antigen negative blood units for HBV DNA among replacement blood donors in a hospital based blood bank in Nigeria

BackgroundHepatitis B virus infection is one of the greatest threats to blood safety all over the world. The laboratory algorithm based on only the detection of hepatitis B surface antigen (HBsAg) leaves a gap for infected HBsAg negative donors to donate blood during the “window period” (WP) and late stages of infection.ObjectiveTo estimate the frequency of the presence of HBV deoxyribonucleic acid (DNA) in HBsAg negative blood units screened using two different assays for HBsAg in a high endemic region.MethodsFrozen serum aliquot of 100 replacement blood donors who donated blood units that were HBsAg negative were retrieved and tested for HBV DNA. Sample positive for HBV DNA was sequenced by Sanger''s method, genotyped and the viral load was determined.ResultsOne sample (1%) was positive for HBV DNA. The HBV viral load of the sample was 768,000 IU/ml. The partial S-gene of the Hepatitis B virus isolated was genotype E using the NCBI viral genotyping tool.ConclusionsThere is still a risk of HBV infected blood unit escaping detection when donor testing is limited to HBsAg screening. The use of NAT which can substantially reduce HBV infected blood donors from the donor pool should be considered.     

BOOK REVIEWS

Book Reviewed in this article: Non-Compliance in Winnicott's Words: A Companion to the Work of D. W. Winnicott by Alexander Newman. Unconscious Logic: An Introduction to Matte Blanco's Bi-Logic and its Uses by Eric Rayner. Sexual Abuse Recalled. Treating Trauma in the Era of the Recovered Memory Debate edited by Judith Alpert. Brief Versus Long Psychotherapy by James Paul Gustafson. What Do Psychoanalysts Want? The Problem of Aims in Psychoanalytic Therapy by Joseph Sandler and Anna Ursula Dreher. The Cosmic Circle: The Unification of Mind, Matter and Energy by R. Langs and A. Badalamenti (with L. Thomson).     

Theory of mind in Asperger's syndrome,schizophrenia and personality disordered forensic patients

Introduction. The ability to conceptualise other individuals' mental states is dependent on having a ‘theory of mind’ (ToM). Individuals with Asperger's syndrome typically display ToM impairments, as do some individuals with schizophrenia, notably those with paranoid delusions. The presenting features of these and other individuals, such as those with some personality disorders, particularly in forensic patients, are often unclear. ToM performance was examined to see whether it could distinguish forensic patients with Asperger's syndrome from other patient groups. Methods. The performance of three male patient groups (N = 39) detained in high security psychiatric care, including those with Asperger's syndrome, schizophrenia (with paranoid delusions and/or auditory hallucinations as their predominant symptoms), or a dissocial and/or borderline personality disorder were compared using the revised eyes task and the modified advanced ToM test. Results. The Asperger's syndrome and schizophrenia groups performed significantly worse than the personality disorder group on both ToM measures. However, the Asperger's syndrome and the personality disorder groups had significantly higher levels of general intellectual functioning than the schizophrenia group. Conclusions. Whilst ToM performance may help to discriminate patients with Asperger's syndrome or schizophrenia from personality disorder ed patients, a wide range in performance made it difficult to specify a patient to a particular group. Theoretical and methodological issues are discussed along with the usefulness of ToM assessments with forensic patients.     

The relationship between cell apoptosis dysfunction and FEN1 E160D mutation in lupus nephritis patients

Objective: This study aims to evaluate the role of FEN1 E160D mutation in lupus nephritis (LN) patients with cell apoptosis dysfunction.

Methods: (1) Cell apoptosis was detected from 50 paraffin samples obtained from renal biopsies of patients with Class IV LN by TUNEL method and the relationship of the systemic lupus erythematosus disease activity index 2000 (SLEDAI 2000) and renal tissue cell apoptotic index (AI) was discussed. (2) FEN1 gene 61563142–61563342 containing E160D were analysed by extracting genomic DNA from peripheral blood collected from the above 50 LN patients and 25 patients with nephrectomy caused by renal trauma. The difference between these two groups was statistically significant.

Results: Cell apoptosis was detected in all patients with LN, and correlation analysis results revealed a positive relationship between SLEDAI 2000 and AI (r?=?0.39, p?=?.032). The FEN1 gene 61563142–61563342 fragment had site mutations at C/??(+61563189), A/T (+61563198), A/??(+61563204), G/T (+61563303), and T/C (+61563304). However, no statistical significance was found between LN patients detected with cell apoptosis and healthy individuals.

Conclusions: This study revealed that cell apoptosis dysfunction plays a key role in the pathogenesis of LN, even though the difference in FEN1 gene 61563142–61563342 between LN patients and healthy individuals was not statistically significant. Larger sample size studies or genome-wide association studies are needed.     

Impaired dendritic cell maturation in response to pandemic H1N109 influenza virus

BackgroundInfection with pandemic A/H1N1/2009 influenza virus led to hospitalisation of patients not expected to be at risk of severe disease from seasonal influenza infection.ObjectivesWe sought to establish whether (i) DC maturation was compromised in patients experiencing severe pandemic influenza infection, (ii) the pandemic virus differed from seasonal influenza virus in its ability to induce DC maturation and (iii) there was an associated inability to activate memory B cells or induce antibody.Study designPeripheral blood mononuclear (PBMCs) cells were sampled from individuals with confirmed acute pandemic A/H1N1/2009 influenza infection or from healthy vaccinated controls. DCs were differentiated from the PBMC and tested for their ability to mature following stimulation with pandemic virus, seasonal H3N2 influenza virus or LPS. Serum samples from the patients were used to assess seroconversion to influenza and the levels of influenza specific memory B cells in PBMC were also determined.ResultsDCs obtained from all individuals exhibited negligible maturation marker upregulation when exposed to pandemic A/H1N1/2009 virus but showed a strong response to the seasonal H3N2 virus and LPS. Robust levels of memory B cell were obtained in both groups and patients seroconverted to the virus.ConclusionsOverall, the ability of patient's DC to mature in response to different stimuli was no different to that of control subjects DCs. Importantly, panH1N109 virus failed to induce substantial DC maturation in any individual, contrasting with seasonal virus, but this did not result in failure to mount memory B cell and antibody responses to the virus.     

Detection of SRV/D shedding in body fluids of cynomolgus macaques and comparison of partial gp70 sequences in SRV/D-T isolates

We previously reported the isolation of a novel subtype of SRV/D-Tsukuba (SRV/D-T) from two cynomolgus monkeys (Macaca facicularis) in the breeding colony of Tsukuba Primate Research Center (TPRC). We surveyed for SRV/D infection in the TPRC cynomolgus colony using SRV/D-specific PCR primer sets designed based on the entire gag region sequence. The only SRV/D subtype detected in the colony was SRV/D-T with a positive infection rate of 22.4% (n = 49). It has been reported that the mode of transmission of SRV/D is via contact with virus shed in the body fluids. In this report, to investigate the infection route of SRV/D-T in monkeys at TPRC, we performed virus isolation and PCR for detection of the SRV/D genome from peripheral blood mononuclear cells (PBMCs), plasma, saliva, urine, and feces. Virus isolation and PCR detection were positive in plasma, saliva, urine, and fecal samples from all monkeys on which virus was isolated from PBMCs. This suggests that the spread of SRV/D-T infection in TPRC is via contact with virus shed in saliva, urine, and/or feces. Also, comparison of sequences of gp70 on multiple SRV/D-T isolates revealed that there was little intra- and inter-monkey variation, suggesting that SRV/D-T is fairly stable.     

APOPTOSIS IN AUTOIMMUNE AND NON-AUTOIMMUNE THYROID DISEASE

The elimination of autoreactive T cells in the thymus involves the process of programmed cell death. Animal model studies, using the lpr and gld strains of mice, have identified FAS receptor (FAS) and FAS ligand (FAS-L) as important components of this mechanism. Whether FAS and FAS-L are also implicated in the autoimmune destruction of a target organ, such as the thyroid, remain hypothetical. An accompanying paper in this issue has addressed the question by FACS and immunocytochemical analysis of FAS expression and apoptosis in thyrocytes grown in culture and in intact thyroid tissues obtained from Hashimoto's thyroiditis, multinodular goitre and Graves' disease. The overall results suggest that the degree of FAS expression on target cells may determine their sensitivity to T-cell mediated cytotoxicity in the absence of perforin or granzyme directed apoptosis mechanisms. © 1997 John Wiley & Sons, Ltd.     

Identification and functional analysis of the putative anti-apoptotic gene iap4 of Spodoptera litura nucleopolyhedrovirus

Baculoviruses possess two types of anti-apoptotic genes, p35 and inhibitor of apoptosis (iap). In this study, we cloned a novel IAP family member, Splt-IAP4, from Spodoptera litura nucleopolyhedrovirus (SpltNPV). ScanProsite analysis of Splt-IAP4 amino acid sequence show that it contain a baculovirus IAP repeat (BIR) motif at the N-terminal portion from 18 to 61 amino acid and a Zinc finger RING motif near its C-terminus. Baculovirus IAPs could be divided into five types from IAP1 to IAP5 according to amino acid sequence homology, so the Splt-IAP4 was grouped into IAP4 because of containing a single BIR motif. Alignment of the six IAP4s in sequenced baculovirus genomes indicated that the Splt-IAP4 gene shared 74% amino acid sequence similarity with Spodoptera littoralis NPV (SpliNPV) IAP4 higher than other baculovirus IAP4 proteins, suggesting evolutionary conservation. In transient expression assay, Splt-IAP4 was not able to suppress apoptosis induced by a mutant AcMNPV deficient in p35 (vAcAnh) infection and rescue the mutant virus replication from apoptosis in Sf-9 cells. Cell viabilities analysis showed that Splt-IAP4 could not inhibit or delay the apoptosis of Sf-9 cells induced by vAcAnh infection. In summary, Splt-IAP4 had no anti-apoptotic function during vAcAnh-infected Sf-9 cells.