Herman Friedman – författare

Biomedical scientists widely acknowledge that individuals' immune respon­ siveness is important in resistance to infections by microorganisms, including fungi. Because of the devastating acquired immunodeficiency syndrome (AIDS) epidemic, caused by the human immunodeficiency retrovirus, it is now accepted that suppressed immune responses, especially cellular immu­ nity, are important contributors to increased individual susceptibility to opportunistic infections-including infections caused by fungi which were at one time thought to be very lowly or nonpathogenic. Within the last few years, there has been an almost explosive increase in interest and studies concerning the nature and mechanisms of the immune response to fungal infections. Many immunologists who are not well versed in mycology have begun to study the nature and mechanisms of antifungal immunity using a wide variety of newer as well as more conventional immunologic technologies, both in vivo and in vitro. Up to the 1980s, however, there was little interest among basic immunologists concerning fungal immunity. This situation has changed dramatically in the past half decade, mainly because of AIDS.

Presenting the basic concepts and clinical implications of respiratory infection, with special emphasis on the role of the immune system, the field's leading researchers contribute detailed chapters on most of the major pathogenic and opportunistic bacteria, fungi, and viruses. Their work will stimulate new research by microbiologists and immunologists, teach clinicians the interaction between microorganisms and the host, and provide health professionals with information necessary to evaluate public health procedures.

DNA tumor viruses have long been useful experimental models of carcinogenesis and have elucidated several important mechanisms of cell transformation. Re­ search in recent years has shown that human tumors have a multifactorial nature and that some DNA tumor viruses may playa key role in their etiology. The aim of this book is to assess our knowledge of DNA tumor viruses by reviewing animal models, mechanisms of transformation, association with human tumors, and possi­ bilities of prevention and control by vaccination. Animal models of tumor virology have contributed significantly to our under­ standing of the epidemiology and pathogenesis of virus-induced tumors. Bovine papillomaviruses induce papillomas in the intestine of cattle. The papillomas undergo a transition to carcinomas in cows feeding on bracken fern, which pro­ duces a toxin with radiomimetic and immunosuppressive functions. This example of cooperation between a virus and chemical carcinogens parallels the cooperative role of human papillomaviruses (HPVs) and herpes simplex virus type 2 (HSV-2) with environmental carcinogens in the pathogenesis of cervical cancer. Likewise, hepatocarcinomas appearing in woodchucks chronically infected by woodchuck hepatitis virus (WIN) provide strong support for the relationship between hepatitis B virus (HBV) infection and human hepatocellular carcinoma. Also, the fact that WIN DNA integrates closely to cellular oncogenes suggests a possible molecular mechanism for the tumorigenesis induced by HBV.

As we approach the end of this millennium, enteric diseases remain impor­ tant public health problems. In many parts of the world, sanitary measures have advanced little over the last century, although some of the governments in those areas are striving to improve facilities for sanitation and to educate their people in proper handling of food, water, sewage, and other modes of transmission of pathogenic microbes. Even in highly developed countries, outbreaks of diarrheal diseases occur today. Globally, the annual morbidity from enteric infections is estimated at several billion and deaths at several million per year. In this volume, descriptions of some of these diseases, of immunity that results from them, of clinical studies that promote under­ standing of individual and community immunity, of molecular factors of pathogenesis, and/or of advances in vaccine development have been pro­ vided by leading researchers. At present, the application of molecular methods is enhancing the identification of protective antigens of many microorganisms. In addition, new methods for design and delivery of vac­ cines are being devised. Perhaps then more effective tools for reducing at least some of these diseases will be available within the next decade. Lois J. Paradise Herman Friedman Mauro Bendinelli vii Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv LOIS J. PARADISE 1. Indigenous Microorganisms as a Host Defense 1 KENNETH H. WILSON 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Composition of Intestinal Biota. . . . . . . . . . . . . . . . . . . . . . . . 2 3. Molecular Approaches to Determine Composition of the Biota . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . 3 4. Role of the Host in Determining the Composition of the Biota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

As a group, rickettsiae, and related bacteria, contain a number of human pathogens that have recently named as causes of 'emerging diseases'. This unique volume offers a thorough and current review of information on the pathogenesis and immune response elicited by members of the genera Rickettsia, Ehrlichia, Coxiella, Orlentia, and Bartonella, in contributions authored by the expert clinicians and researchers who work with these organisms.

Busy clinicians and health practitioners recognize the importance of speedy detection of pathogens to impede the further spread of infection, and to ensure their patients' rapid and complete recovery. This reader-friendly reference is a unique collection of the newest and most effective diagnostic techniques currently in use in clinical and research laboratories. Instructive commentary regarding the application of these often complex methods is provided. This essential text aids readers in selecting the most efficient method, finding the necessary resources, and avoiding the most common pitfalls in implementation.

Although virology and immunology are now considered separate disciplines, history shows that these areas ofinvestigation always overlapped and one cannot really exist without the other. This trend has become particularly significant and fruitful in the past few years in the area of herpesvirus research. The genomes of the most important herpesviruses have been sequenced, a significant portion of their genes have been identified, and many secrets of regulation of gene expr- sion have been unraveled. Now this progress sets the stage for a true revolution in herpesvirus research: analysis of interactions between the host and the virus. Because herpesviruses can induce, suppress, and fool the immune system, the most productive herpesvirologists are also expert immunologists, and the current results ofthis interdisciplinary effort are truly remarkable. Because herpesviruses cause many important human diseases, the devel- ment of vaccines against these agents is a very significant goal. This effort is also very challenging because of the complexity of herpesviruses and the lack of sufficient information about immune responses. The remarkable ability of herpesviruses to escape immune responses is - other feature that brings immunology and virology together. Herpesviruses - code many proteins that interact with and down-regulate some key elements of the immune system. Thisproperty of herpesviruses represents amajor challenge in developing strategies against these viruses. On the positive side, these viral proteins also provide novel tools for analyzing specific immune reactions and molecular mechanisms.

This collection of works brings together experts in the field of human retroviral pathogenesis, vaccine development, and the clinical treatment of AIDS. One of the greatest problems facing the development of an effective vaccine against HIV-1 is the ability of the virus, particularly in the immunogenic envelope glycoprotein, to undergo amino acid hypervariability, thus making a vaccine against one envelope glycoprotein ineffective against other viruses due to their mutability.

Introduction and Perspectives This volume is based on the proceedings of the 7th annual symposium on the topic Neuroimmune Circuits, Infectious Diseases and Drugs of Abuse, Bethesda, Maryland, Oc- ber 7–9, 1999. This symposium, as in the past, focused on newer knowledge concerning the relationship between the immune and nervous systems with regards to the effects of drugs of abuse and infections, including AIDS, caused by the immunodeficiency virus. Presentations discussed the brain-immune axis from the viewpoint of drugs of abuse rather than from the subject of the brain or immunity alone. The major aim of this series of conferences has been to clarify the consequences of immunomodulation induced by drugs of abuse in regards to susceptibility and pathogenesis of infectious diseases, both in man and in various animal model systems. The recreational use of drugs of abuse such as morphine, cocaine, and marijuana by large numbers of individuals in this country and around the world has continued to arouse serious concerns about the consequences of use of such drugs, especially on the normal physiological responses of an individual, including immune responses. Much of the recent data accumulated by investigators show that drugs of abuse, especially opioids and cannabinoids, markedly alter immune responses in human populations as well as in experimental animals, both in vivo and in vitro.

Staphylococcus aureus is now acknowledged as being the most important bacterial pathogen of humans. It usually produces localized disease but can be rapidly invasive, spreading through the tissues, invading bone, and seeding the bloodstream to produce a fulminant picture of septic shock, disseminated intravascular coagulation, and rapid death. Moreover, most strains of staph infections are becoming resistant to most antibiotics, thus posing a significant problem for hospitals and health care facilities. This book, a volume in the Infectious Agents and Pathogenesis series, presents chapters by the major researchers in the field.

There is overwhelming evidence that Helicobacter pylori is the major cause of chronic active gastritis and that it may further predispose to peptic ulcers, of which there are several thousand cases in the US each year. The most severe clinical outcomes of H. pylori infection are mucosa-associated lymphoid tissue lymphoma and gastric cancer. Because of these findings, the implications for cancer aetiology are intriguing. This book, a volume in the "Infectious Agents and Pathogenesis" series, presents chapters by major researchers in the field, including Dr. Barry Marshall whose research was responsible for establishing the linking of gastric ulcers with the H. pylori bacterium.

Busy clinicians and health practitioners recognize the importance of speedy detection of pathogens to impede the further spread of infection, and to ensure their patients'' rapid and complete recovery. This reader-friendly reference is a unique collection of the newest and most effective diagnostic techniques currently in use in clinical and research laboratories. Instructive commentary regarding the application of these often complex methods is provided. This essential text aids readers in selecting the most efficient method, finding the necessary resources, and avoiding the most common pitfalls in implementation.

Although virology and immunology are now considered separate disciplines, history shows that these areas ofinvestigation always overlapped and one cannot really exist without the other. This trend has become particularly significant and fruitful in the past few years in the area of herpesvirus research. The genomes of the most important herpesviruses have been sequenced, a significant portion of their genes have been identified, and many secrets of regulation of gene expr- sion have been unraveled. Now this progress sets the stage for a true revolution in herpesvirus research: analysis of interactions between the host and the virus. Because herpesviruses can induce, suppress, and fool the immune system, the most productive herpesvirologists are also expert immunologists, and the current results ofthis interdisciplinary effort are truly remarkable. Because herpesviruses cause many important human diseases, the devel- ment of vaccines against these agents is a very significant goal. This effort is also very challenging because of the complexity of herpesviruses and the lack of sufficient information about immune responses. The remarkable ability of herpesviruses to escape immune responses is - other feature that brings immunology and virology together. Herpesviruses - code many proteins that interact with and down-regulate some key elements of the immune system. Thisproperty of herpesviruses represents amajor challenge in developing strategies against these viruses. On the positive side, these viral proteins also provide novel tools for analyzing specific immune reactions and molecular mechanisms.

The discovery of the human T cell leukemia virus type I in the late 1970s heralded a new era in retrovirology. For the first time, it was demonstrated that a retrovirus could play a role in the development of a human disease, in this case adult T cell leukemia (ATL). Several years later, the acquired immunodeficiency syndrome (AIDS) epidemic began, and it was dem- strated that a retrovirus, originally designated the human T cell lymp- tropic virus type 3, was the causal agent of this syndrome. This virus, later named the human immunodeficiency virus type 1 (HIV-1), has since been extensively studied in terms of its pathogenesis as well as its ability to elicit immune responses. In that time, a tremendous amount of information has been obtained about the virus. Although recent drug regimens have been useful in significantly lowering viral loads and perhaps maintaining an asymptomatic state among individuals infected with HIV-1, an established “cure” for AIDS eludes us. In addition, the effective drug therapies are very expensive, and are not available to infected people in the third world, where greater than 90% of new infections occur. Furthermore, the development of viral resistance against the drug therapies is an additional concern. Despite extensive study, no effective vaccine has been developed. One of the problems in developing an effective vaccine against HIV-1 is the ability of the virus, particularly in the immunogenic envelop glycoprotein, to undergo amino acid hypervariability.

Staphylococcus aureus is now acknowledged as being the most important bacterial pathogen of humans. It usually produces localized disease but can be rapidly invasive, spreading through the tissues, invading bone, and seeding the bloodstream to produce a fulminant picture of septic shock, disseminated intravascular coagulation, and rapid death. Moreover, most strains of staph infections are becoming resistant to most antibiotics, thus posing a significant problem for hospitals and health care facilities. This book, a volume in the Infectious Agents and Pathogenesis series, presents chapters by the major researchers in the field.

Introduction and Perspectives This volume is based on the proceedings of the 7th annual symposium on the topic Neuroimmune Circuits, Infectious Diseases and Drugs of Abuse, Bethesda, Maryland, Oc- ber 7–9, 1999. This symposium, as in the past, focused on newer knowledge concerning the relationship between the immune and nervous systems with regards to the effects of drugs of abuse and infections, including AIDS, caused by the immunodeficiency virus. Presentations discussed the brain-immune axis from the viewpoint of drugs of abuse rather than from the subject of the brain or immunity alone. The major aim of this series of conferences has been to clarify the consequences of immunomodulation induced by drugs of abuse in regards to susceptibility and pathogenesis of infectious diseases, both in man and in various animal model systems. The recreational use of drugs of abuse such as morphine, cocaine, and marijuana by large numbers of individuals in this country and around the world has continued to arouse serious concerns about the consequences of use of such drugs, especially on the normal physiological responses of an individual, including immune responses. Much of the recent data accumulated by investigators show that drugs of abuse, especially opioids and cannabinoids, markedly alter immune responses in human populations as well as in experimental animals, both in vivo and in vitro.

Chlamydia pneumoniae is a bacteria that is most commonly known for causing colds and pneumonia. However, researchers have recently found a link between C. pneumoniae and atherosclerosis, a clogging of the arteries that causes heart attack and stroke. In addition, ongoing research is showing that certain strains may play a role in asthma, multiple sclerosis, Alzheimer's disease, and arthritis. This volume, part of the Infectious Agents and Pathogenesis series, is a complete portrait of C. pneumoniae and what is currently known about it.

The use of recreational drugs of abuse by large numbers of individuals in this country and abroad has aroused serious concerns about the consequences of this activity. For example, it is recognized that marijuana is currently widely used as a recreational drug in the United States as well as other countries. Similarly, abuse of cocaine, especially crack cocaine, is considered to be an epidemic. “The war on drugs” by the US Government was directly aimed at the illicit use of cocaine, marijuana, and opiates as well as other drugs of abuse. Furthermore, alcohol is also considered a major problem of abuse in this country as well as in many other countries. It is estimated there are at least 10 million alcoholics in the United States alone. A signi?cant portion of those hospitalized with infectious diseases are alcoholics. Similarly, there have been many reports of association between marijuana use and increased susceptibility to infection as well as a re- tion between use of opiates and infections. The relationship between drug abuse and increased incidence of various infections has stimulated increased investi- tion of whether and how such drugs affect immune function, especially imp- tant for resistance against infectious agents. During the last decades, a wide variety of studies have shown that drugs of abuse, including marijuana, cocaine, or opiates, as well as alcohol, alter both neurophysiological as well as pathological responses of individuals.

The use of recreational drugs of abuse by large numbers of individuals in this country and abroad has aroused serious concerns about the consequences of this activity. For example, it is recognized that marijuana is currently widely used as a recreational drug in the United States as well as other countries. Similarly, abuse of cocaine, especially crack cocaine, is considered to be an epidemic. “The war on drugs” by the US Government was directly aimed at the illicit use of cocaine, marijuana, and opiates as well as other drugs of abuse. Furthermore, alcohol is also considered a major problem of abuse in this country as well as in many other countries. It is estimated there are at least 10 million alcoholics in the United States alone. A signi?cant portion of those hospitalized with infectious diseases are alcoholics. Similarly, there have been many reports of association between marijuana use and increased susceptibility to infection as well as a re- tion between use of opiates and infections. The relationship between drug abuse and increased incidence of various infections has stimulated increased investi- tion of whether and how such drugs affect immune function, especially imp- tant for resistance against infectious agents. During the last decades, a wide variety of studies have shown that drugs of abuse, including marijuana, cocaine, or opiates, as well as alcohol, alter both neurophysiological as well as pathological responses of individuals.

An AIDS vaccine is still elusive and HIV treatment continues to develop multidrug resistance at alarming rates. Because of the similarities between HIV and immune deficiency infections in a variety of animals, it is only natural that scientists use these animals as models to study pathogenesis, treatment, vaccine development and many other aspects of HIV.Part of the series Infectious Agents and Pathogenesis, this volume reviews the immune deficiency virus in a variety of hosts. Pathogenesis, vaccine and drug development, epidemiology, and the natural history of the monkey, mouse, cat, cow, horse, and other animal viruses are detailed and compared to HIV. Also included are chapters on the history and future of animal models, as well as a chapter on ethical and safety considerations in using animal models for AIDS studies.

The threat of bioterrorism has become a major challenge for the twenty-?rst century. However, the potentials of infectious agents as bioweapons have been recognized for centuries. Throughout history there have been attempts to i- tiate infectious disease outbreaks and epidemics during warfare. In the last decade the attention of the biomedical community, as well as governments and the United Nations, has increasingly focused on the threat of bioterr- ism, especially the use of biological and/or chemical weapons against military and civilian populations. As an example, there is now much interest conce- ing microbial infection and bioterrorism in the medical microbiology and - munologycommunities. Thisvolumeaddressessuchconcernsandemphasizes bothbasicandclinicalconcepts,aswellasproblematicimplicationsofinfection by various microbes now recognized as potential bioterrorism agents. The ?rst chapter by Drs. Andrew Canons, Philip Amuso, and Burt And- son from the University of South Florida is an overview of the biotechnology of bioterrorismbothinthepublichealthresponsetopossibleactsofbioterrorism, aswellasfortheconcernsaboutthemisuseofbiotechnology.Thesecondch- ter is a historical perspective of microbial bioterrorism by Dr. Steven Morse, Director of the Bioterrorism Division at the Center for Disease Control and Prevention in Atlanta, GA. This chapter describes in detail historical aspects concerning the early use of biological agents in warfare, development and international conventions to prohibit the use of such weapons, and a brief - scription of important incidents of infectious agents as bioterrorist agents and use during the last few centuries. The next chapter by Dr. Sandra Gompf from the University of South Florida discusses the role of public health physicians and infectious diseases specialists in the control of microbial bioterrorism.

Legionella pneumophila is an emerging human pathogen that resides in natural environments as a parasite of freshwater. There have been new developments in this field including the publication of three whole genome sequences, the discovery of a developmental cycle and novel cyst-like highly infectious form, and the bacteria have been used as a probe for macrophage cellular function to unravel fundamental new knowledge in the area of cellular biology. Legionella has also become a model system for the study of innate as well as adaptive immunity. Information on Legionella continues to increase in the U.S. and abroad. Columbia University has started the first Legionella Genome Project with a multi-million dollar grant from the NIH. In addition, The European Working Group for Legionella infections was formed in 1986. Members are scientists with an interest in improving knowledge and information on the clinical and environmental aspects of legionnaires' disease through developments in diagnosis, management and treatment of the disease. The volume brings together all of the lastest research on this pathogen, the interest in which is rapidly growing.