An essential component of inflammation is the migration of circulating leukocytes from blood into tissues. This process is characterized by a multistep paradigm of sequential cell adhesion and activation events that lead to the extravasation of specific leukocyte subsets to different tissues in health and disease. The first step of leukocyte extravasation, the rolling of leukocytes, is primarily mediated by the interactions of selectins and their ligands. It has recently become evident that fucosyltransferases are crucial for selectin ligand synthesis, inflammation, and skin homing. This book provides an in-depth overview of the mechanisms of leukocyte trafficking and of the molecular mechanisms of selectin/selectin ligand interactions and discusses options for pharmacological intervention to treat inflammatory diseases.

This acclaimed core text in Dermatology now returns in a thoroughly revised and refocused format. Its clear structuring will enable all readers to find quickly what they need to know and to see how each part fits into the whole, offering a consistent guide for residents wanting a reliable revision aid for the core topics in Dermatology and for physicians in other disciplines interested in individual topics (particularly family physicians specializing in the diagnosis of skin cancer).

This series is intended particularly for young doctors working in hospitals and in primary care and for those involved in training them. The series has been designed to cover growing points in medicine and the authors have been chosen, not just because of their expertise, but also because they are working both in hospitals and the community and are thus sensitive to the problems and needs of doctors in both areas.

Humanhairisananocompositebiological?ber. Maintainingthehealth,feel,shine, color,softness,andoverallaestheticsofthehairishighlydesired. Haircarepr- ucts such as shampoos and conditioners, along with damaging processes such as chemical dyeing and permanent wave treatments, affect the maintenance and groomingprocessandareimportanttostudybecausetheyaltermanyhairprop- ties. Nanoscalecharacterizationofthecellularstructure,mechanicalproperties,and morphological, frictional,andadhesive properties(tribologicalproperties)ofhair areessentialtoevaluateanddevelopbettercosmeticproductsandtoadvancethe understandingofbiologicalandcosmeticscience. Theatomic/frictionforcemic- scope(AFM/FFM)andnanoindenterhavebecomeimportanttoolsforstudyingthe micro/nanoscalepropertiesofhumanhair. Inthisbook,wepresentacomprehensive review of structural, nanomechanical, and nanotribological properties of various hairandskinasafunctionofethnicity,damage,conditioningtreatment,andvarious environments. Variouscellularstructuresofhumanhairand?nesublamellarstr- turesofthecuticleareidenti?edandstudied. Nanomechanicalpropertiessuchas hardness,elasticmodulus,tensiledeformation,fatigue,creep,andscratchresistance arediscussed. Nanotribologicalpropertiessuchasroughness,friction,andadhesion are presented, as well as investigations of conditioner distribution, thickness, and bindinginteractions. Tounderstandtheelectrostaticchargebuilduponhair,surface potentialstudiesarealsopresented. Thebookshouldserveasareferencebookonthebiophysicsofhumanhairand hairtreatments. TheresearchreportedinthisbookwassupportedbyProcter&GambleCo. in Cincinnati,Ohio,andKobe,Japan. IwouldliketothankCarmenLaTorrewhohad assistedinvariouspublicationsonhairresearch. Iwouldalsoliketothankmywife Sudha,whohasbeenforbearingduringthepreparationofthisbook. Powell,OH BharatBhushan November2010 v Contents 1 Introduction-Human Hair, Skin, and Hair Care Products...1 1. 1 HumanHair ...1 1. 1. 1 TheCuticle ...3 1. 1. 2 TheCortexandMedulla...6 1. 2 Skin...7 1. 3 HairCare:CleaningandConditioningTreatments,andDamaging Processes ...10 1. 3. 1 CleaningandConditioningTreatments:Shampoo andConditioner...13 1. 3. 2 DamagingProcesses...18 1. 4 OrganizationoftheBook ...19 2 Experimental Methods...21 2. 1 ExperimentalApparatuses...23 2. 2 ExperimentalProcedure ...26 2. 2. 1 StructuralCharacterizationUsinganAFM...26 2. 2. 2 SurfacePotentialStudiesUsingAFM-Based KelvinProbeMicroscopy...29 2. 2. 3 NanomechanicalCharacterizationUsingNanoindentation ...30 2. 2. 4 InSituTensileDeformationCharacterizationUsingAFM ...32 2. 2. 5 Macroscale Tribological Characterization UsingaFrictionTestApparatus...33 2. 2. 6 Micro/nanotribologicalCharacterizationUsinganAFM...35 2. 3 HairandSkinSamples ...41 3 Structural Characterization Using an AFM ...45 3. 1 StructureofHairCrossSectionandLongitudinalSection ...45 3. 1. 1 CrossSectionofHair...45 3. 1. 2 LongitudinalSectionofHair...45 3. 2 StructureofVariousCuticleLayers...48 3. 2. 1 VirginHair...48 vii viii Contents 3. 2. 2 ChemicallyDamagedHair...50 3. 2. 3 Conditioner-TreatedHair...52 3. 2. 4 EffectofHumidityonMorphologyandCellularStructure ofHairSurface...54 3. 3 Summary...55 4 Nanomechanical Characterization Using Nanoindentation, Nanoscratch, and AFM...57 4. 1 Hardness,Young'sModulus,andCreep...

Jacques Barzun, the noted Columbia University historian of ideas and culture, once described the feeling that some people experience when they come upon a new reference book. He wrote: "Hand over to one of us a new Dictionary, "Companion," or Guide, and our eyes first light up and then turn dreamy: we have seized the volume and are off, arm in arm with the guide i or companion. ..." The book now in your hands made my eyes light up. Thyroid Disorders with Cutaneous Manifestations is that kind of book. Heymann, who has been fascinated by this sometimes controversial subject for decades, has brought not only his own expertise, but that of many experts from the fields of the skin and the thyroid gland. Steven Jay Gould wrote about overlapping and nonoverlapping magisteria-this book demonstrates just how much important overlap there is. But it also covers the basics in such a way that dermatologists can find what they need to know about the thyroid and thyroidologists can find what they need to know about the skin. Thyroid Disorders with Cutaneous Manifestations falls neatly into the tra- tion of medical monographs that become standards. They fulfill the roles of gathering, digesting, and synthesizing current knowledge, and they do so in a way that review articles cannot approach and that the scientific literature is not designed to accomplish.

Major skin diseases, including acne, psoriasis and eczcma, affect the majority of the population at some time in their lives. In general, these diseases are physically and psychologically disfiguring for the sufferers; furthermore, by their very chronic nature skin diseases, unlike most other disease processes, present both acute and chronic therapy problems. In addition, the chronic nature of these diseases can present certain economic problems. Firstly, chronic therapy is becoming increasingly expensive and secondly, patients adhering to a strict treatment regimen will frequently be absent from their gainful employment for either medical consultation or treatment. Given that in all NATO countries the average age of the population is continually increasing, these chronic skin diseases will increase in importance in the coming years. Furthermore, as the average population age increases, additional disease processes such as skin photodamage and carcinogenicity risk becoming major areas of therapeutic concern. This book reviews in detail the major scientific areas of interest for research and clinical scientists working in skin pharmacology and toxicology. The basic principles relating to an understanding of how drugs and chemicals may influence either the skin or the body as a whole are discussed in detail by recognized international scientific experts.

Liposuction began as a contouring procedure but has evolved into the treatment of obese patients, gynecomastia, ptosis, macromastia, and even patients who have complications from heart disease or diabetes. Other disorders such as axillary sweat hypersecretion, lipomas, and angiomas are also potential disorders that may be treated with liposuction.

Physicians performing liposuction must be adequately trained and experienced in the potential and actual complications before attempting to perform liposuction. Patient safety is the most important aspect of all surgeries, but especially of cosmetic surgery, which is an elective procedure.

New technology helps improve results but experience, care, and skill of the cosmetic surgeon is necessary to obtain optimal results that satisfy the patient.

The contributors to this book have spent time and effort presenting the cosmetic and plastic surgeon as much information as possible on the techniques and uses of liposuction for cosmetic and non-cosmetic surgery purposes.

Skin diseases caused by aquatic organisms are continually on the increase owing to the great number of people who now converge on the hydrosphere for holidays, sports and professional activities. Aquatic skin diseases are no longer only a seasonal affliction but can be observed at any period, thanks to the tourist boom promoting aquatic holidaymaking throughout the year. This book aims to contribute to the knowledge of some aquatic animals that have only developed a poisonous apparatus to protect themselves and adapt to their environment, as well as of the various clinical pictures induced by different pathogenic mechanisms. Besides the afflictions caused by biotoxins, skin reactions to microscopic organisms present in seawater, freshwater, swimming pools and aquariums are described, together with some non-biotic forms induced by direct contact with salt and freshwater. A better knowledge of the aquatic environment may help people to enjoy this enthralling habitat at lesser risk.

The Microsystems Series has as its goal the creation of an outstanding set of textbooks, references, and monographs on subjects that span the broad field of microsystems. Exceptional PhD dissertations provide a good starting point for such a series, because, unlike monographs by more senior authors, which must compete with other professional duties for attention, the dissertation becomes the sole focus of the author until it is completed. Conversion to book form is then a streamlined process, with final editing and book production completed within a few months. Thus we are able to bring important and timely material into book form at a pace which tracks this rapidly developing field. Our first four books in the series were drawn from the more physics-oriented side of the microsystems field, including such diverse subjects as computer-aided design, atomic-force microscopy, and ultrasonic motion detection. Now, with Sangeeta Bhatia's work, we enter the realm of biology. Her use of artifically structured substrates to encourage the liver cells to form orderly assemblies is a fine example of how microfabrication technology can contribute to cell biology and medicine. I am pleased to be able to add this very new and very interesting work to the Microsystems Series. Stephen D. Senturia Cambridge MA Microfabrication in Tissue Engineering and Bioartificial Organs Foreword One of the emerging applications of microsystems technology in biology and medicine is in the field of tissue engineering and artificial organs. In order to function, cells need to receive proper signals from their environment.

The book provides a comprehensive overview of the current state, and the new concepts for the future directions of modern cancer therapy. Bringing together all the relevant aspects from basic and applied science, and the clinical experiences of this new direction in medicine, it is an up-to-date summary of the activities in the field and will be the basis for evaluating future progress in this area.

This method of local anaethesia, developed by a dermatologist and a pharmacologist, is presented to demonstrate its use in cosmetic liposuction and other procedures. Richly illustrated to show details of the technique and with serialphotographs of many clinical cases, the book explains the advantages of this new technique and provides practical instruction in how to perform it.

The disciplines of rheumatology and dermatology are involved in the care of several diseases that share cutaneous and locomotor as well as, quite often, systemic involvement. While traditionally remaining separate, it has long been recognized that there are several areas of common interest in these two specialties. Indeed, this had been realized by sev- eral far-sighted physicians, both rheumatologists and dermatologists, such asG. Rodnan and 1. Gilliam. A number of books have been published over the past few years specifi- cally dealing with skin involvement in the connective tissue diseases, both inherited and acquired. These include The Skin in Rheumatic Disease, by C. R. Lovell, P. 1. Maddison, and G. V. Campion (Chapman and Hall Medical, 1990), Connective Tissue Diseases o(the Skin, edited by C. M. Lapiere and T. Krieg (Marcel Dekker, Inc. 1993), and Cutaneous Manifestations of Rheumatic Diseases, edited by R. D. Sontheimer and T. T. Provost (Wil- liams and Wilkins, 1996). However, despite this shared interest, meetings combining the two specialties were generally limited to small interest groups. It had long been felt that a workshop should be organized that could bring together the views of specialists from the two areas and focus on the challenges that this common ground brings to these two disciplines.

Biometrics in dermatology is an essential tool where data evaluation results in valid interpretations. This book will be the first in this area. One part of the book will describe principal aspects of dermatological research focussing on practical advice. A special part will cover applied biometrics to provide the clinician and researcher with state-of-the-art guidelines to assess the severity of common skin diseases. An additional aspect that will be of interest to pharmacologists addresses pharmacologic assays.

Metastases determine malignancy. The main attention so far has been focused upon organ metastases. The molecular mechanisms thereof, while far from being totally elucidated, are increasingly well understood. Modern diagnostic tools now enable detection and precise localization of small lesions. In contrast, our knowl edge and diagnostic capabilities regarding metastatic spread to the'lymphatic system are rather limited. However, there have re cently been a number of interesting advances. It is the aim of this volume to submit these developments to detailed analysis. The therapeutic relevance of enhanced sensitivity in detection of lymph node metastases has to be considered in the light of in creased morbidity versus eventual prognostic improvements by modification of therapy. An interesting concept which might im prove diagnostic accuracy while reducing operative morbidity is the "sentinel node" technique. Surgical standards are lacking, however, and many fundamental questions pertaining to precise lymphatic mapping remain unanswered. Whether the sentinel node concept is of general relevance or whether it is applicable in only a few organs remains to be determined. This book offers intensive discussion of the concept from methodological and tu mor biological viewpoints. World-renowned experts with long term involvement in related basic and clinical research provide the reader with a broad survey of actual knowledge together with a critical appraisal of recent and future developments. We sincerely hope this book succeeds in providing an outlook as a reference for all clinicians on future prospects and serving and researchers in this extremely important field.

Allergy is one of the major health problems of most modern societies. Allergic diseases have increased in prevalence during the last decades; the reasons for this increase are unknown, there are only hypothetical concepts for explanation. The series New Trends in Allergy now covers five volumes origin- ing from special international symposia, started in 1980 and held every 5 years, which highlight specific areas of progress in allergy research and practice. The idea behind the 5-year interval between these s- posia is that real new developments do not occur very often and c- tainly not every year. The contents of this book focus on specific areas where progress in allergy research has shown fascinating developments, such as: - Elucidation of the complex genetic basis of atopy - The influence of environmental pollutants as well as natural biolo- cal environmental factors on allergy - Gene-environment interactions in the development of allergy - Psycho-neuro-immunological aspects of allergic sensitisation and disease - The nature and function of dendritic cells in skin and mucous m- branes - Interactions between lymphocytes and effector cells, such as mast cells, eosinophils and neutrophils - Allergen carriers, allergen release and bioavailability, allergen str- ture - Atopic eczema - Asthma and rhinoconjunctivitis - Food allergy and anaphylaxis - Pharmacotherapy - Unspecific (e. g.

It is remarkable how much we take for granted the tremendous energy and vitality that the sun provides earth's inhabitants. As we enter the new millennium, it is worthwhile to review how our ancestors perceived the biologic effects of sunlight, and how science and medicine have advanced our knowledge about the biologic effects of light. At the turn of the century, a multitude of investigators explored the use of sunlight and artificial radiation for treating a multitude of diseases. These explorations gave rise to photodynamic therapy, phototherapy, and chemophototherapy. However, enthusiasm for using sunlight and artificial radiation to treat disease was dampened with the birth of pharmacology. It was the goal of the Fifth International Arnold Rikli Symposium on the Biologic Effects of Light, held in Basel, Switzerland, on November 1-3, 1998, to review the history of phototherapy and have some of the world's leading experts on the biologic effects of light provide new perspectives on the positive and negative effects of light. The general topics included a broad range of biologic effects of sunlight, artificial ultraviolet radiation and electromagnetic radiation. Special sessions on radiation and vitamin D and bone health, photoimmunology, biopositive effects of UV radiation, effects of electromagnetic currents and fields, and ocular and non-ocular regulation of circadian rhythms and melatonin, should be of particular interest to readers of Biologic Effects of Light.

Proof of the efficacy of dermatological products is a prerequisite for clinical testing and registration. Now, efficacy claims for cosmetics must be equally substantiated. This book provides a concise, practical but comprehensive overview of experimental models used to screen, develop and select dermatological and cosmetic formulations. The authors are recognized specialists in their field and use a standardized approach to the projects facilitating the reading for the stressed scientist, for the R+D managers general view as well as for the beginners in the field.

This book is based upon a series of papers originally presented at a NATO Advanced Studies Workshop of the same title held at the study Center HI Cappuccini," a converted monastery in San Miniato, a small village located between Pisa and Florence, Italy, in October 1991. Authors were asked to submit their completed chapters by the following February; these were then scanned onto computer disks, edited and returned to the authors for final revision, and updating, with a final deadline of February 1993. The authors were encouraged to make whatever modifications they wanted, especially regarding updating their chapters, with an eye to making the final product both comprehensive and current. In this we succeeded beyond our expectations, with most chapters extensively altered and many completely re-written and significantly expanded. Thus, although the original meeting was held in 1991, the chapters in this volume may be regarded as current from at least February, 1993, with some of the final updated revisions received as late as July, 1993. This book, as agreed in our original contract, has been delivered to the publisher "camera-ready. " This means that all of the scanning, editing, proofing and typesetting were done here, by the office of the Department of Dermatology at the New Jersey Medical School. We essentially produced the book, which the publisher, for the most part, then photocopied. This has been an enormous burden, borne mainly by my colleague in this division, Robert A.

Over the generations the skin has been the site for immunization against smallpox. This method of immunization was described in a letter written by Lady Mary Montagu on April 1, 1717 in Adrianopole, Turkey: "The small-pox, so fatal, and so general amongst us, is here entirely harmless by the invention of ingrafting, which is the term they give it. . . The old woman comes with a nut-shell full of the matter of the best sort of small-pox . . . She immediately rips open (the skin) with a large needle . . . and puts into the vein as much venom as can lie upon the head of her needle, and after binds up the wound. There is no example of anyone that died of it; and you may believe that I am satisfied of the safety of this experiment since I intend to try it on my dear little son" (Letters from the right Honourable Lady Mary Montagu 1709-1762. Published by J. M. Dent and Co. London, 2nd edition, September, 1906, p. 124. ) The "variolation" method was, 80 years later, markedly improved by the use of cowpox virus, as reported by Edward Jenner in 1796. The successful method of intradermal immunization against smallpox and later against other virus diseases is in fact based on the presence of anitigen-presenting dendritic cells in the skin.

Significant progress has been made in recent years in understanding the origins of cutaneous maligant melanoma. Knowledge of the relationship between solar radiation and melanoma has changed and it now appears that both the character and timing of exposure may be more important than total cumulative dose in accounting for risk. The melanoma-sunlight model may prove an instructive heuristic exercise for environmental epidemiology, as we currently tend to restrict ourselves to a search for uniform total dose--response relationships between cancers and suspected environmental carcinogens. The study of the relationship between acquired melanocytic nevi and melanoma has led to useful new information about predictors of melanoma risk, and in addition has opened new perspectives on the development of nevi in children. Definition of the factors for nevus development in children may lead to the possibility of primary prevention programs for melanoma in younger generations of children. Recent new evidence suggests that certain occupational groups may be at elevated risk of melanoma. A great deal of work is going into the study of ways of screening high risk populations in order to detect melanoma at its earliest stages when current treatment protocols are most effective. The visibility of lesions on the skin challenges classical definitions of early detection and screening in epidemiology.

The basic principles of the phenomenon "erection" have been known since the pioneering work of Kolliker, Eckhard and Langley in the nineteenth century. Nonetheless, under the influence of Freud, erectile dysfunction was predominantly at tributed to psychogenic factors. A more liberal perception of sexuality since the 1960s, the development of new and refined diagnostic techniques, and the expansion of basic research activity resulted in a new concept of erectile dysfunction, identifying arteriogenic, venogenic, endocrinologic or myopathic (cavernous smooth muscle dysfunction) factors. From this research other considerations such as autonomic innervation, cavernous endo thelial intactness or impaired neurotransmitter pool are being introduced into routine clinical assessment. A reevaluation of psychogenic etiology with a consequential new concept of psy chogenic impotence is on the rise. In this book the new concepts of basic knowledge on cavernous smooth muscle function and its supraspinal, spinal, and local control; the new diagnostic approaches in psychogenic and autonomic factors; and the new developments of reconstructive therapeutic options for the patient have been tied together. Outstanding and internationally renowned experts in the field of erectile dysfunction have given detailed insight into the latest basic and clinical developments. Well-established diagnostic and thera peutic techniques are presented by experienced colleagues. We hope that this book will help the reader to get an overview of the current concepts of erection. Furthermore, we hope that international collaboration in basic and clinical research in the field of erectile dysfunction will render an update necessary in the near future.

In the future' the decade of the 1990s will likely be viewed as a Golden Age for retinoid research. There have been unprecedented research gains in the understanding of retinoid actions and physiology; since the retinoid nuclear receptors were first identified and the importance of retinoic acid in develop mental processes was first broadly recognized in the late 1980s. Between then and now, our knowledge of retinoid action has evolved from one of a near complete lack of understanding of how retinoids act within cells to one of sophisticated understanding of the molecular processes through which retinoids modulate transcription. In this volume, we have tried to provide a comprehensive update of the present understanding of retinoid actions, with an emphasis on re cent advances. The initial chapters of the volume, or Section A, focus on the physicochemical properties and metabolism of naturally occurring retinoids: - N OY provides an uncommonly encountered view of retinoid effects from the perspective of the physiochemical properties of retinoids. - V AKIANI and BUCK lend a perspective on the biological occurrence and actions of retro- and anhydro-retinoids. Section B considers both the retinoid nuclear receptors and their mechanisms of action as well as synthetic retinoids that have been used exper imentally to provide mechanistic insights into receptor actions and have potential therapeutic use for treating disease: - PIEDRAFITA and PFAHL provide a comprehensive review of retinoid nuclear receptor biochemistry and molecular biology.

Until now, the general belief has been that premature baldness (male pattern bald- ness: M.P.B., or androgenetie alopeeia) is a hereditary eondition that progresses with age and for which there is no eure. If the father is bald, it is assumed that the ehild may also be destined to be bald sometime in the future. The existing theory throughout the world is that the eentral portion of the hair follicle is the hair root, and hair ean never regrow if the hair root has been removed. Dr. Inaba has introdueed a new theory that the eentral portion of the hair folliele is not only the hair root but the upper isthmal portion elose to the duet opening of the sebaeeous gland. This is a totaUy new understanding of the hair growth mechanism and the hair eyele. In his experienee in the surgieal removal of the sweat glands, whieh also removes the hair root, Dr. Inaba has found inereasing evidenee that hair regrows if the sebaeeous gland is left intaet.

It is a great pleasure for me to see this work in print. As outlined by Dr. Traupe, at least 20 different types of ichthyosis have been identified to date. This book will effectively help to establish a correct diagnosis, as a basis for genetic counseling. Dr. Traupe proposes a new classification of the ichthyoses, based on reason able clinical criteria. He lets the reader share in his enormous knowledge and safely guides him through the difficult field of nomenclature. He describes the particular nature of these scaling disorders in a manner as simple as possible. During the last few years, research on ichthyosis has become a fascinating scientific challenge due to the introduction of novel investigative approaches. The main advantage of this book lies in the fact that the author successfully combines recent achievements made in lipid analysis, enzymology, electron microscopy, and molecular genetics. Heiko Traupe began his career in dermatology 11 years ago, as a resident in the Department of Dermatology in Munster. As we were both interested in the genetic aspects of skin diseases, this was the starting point of a most fruitful collaboration, which is still continuing. During our common work in Munster, Dr. Traupe was able, thanks to his unceasing clinical curiosity, to describe many novel aspects within the field of ichthyosis, and I took pride in coauthoring papers on new items such as cryptorchidism as a fea ture associated with X-linked recessive ichthyosis, autosomal dominant lamellar ichthyosis, and alopecia ichthyotica."