General histological woes: Definition and classification of tissues.

The modern view that the human body is composed of tissues and body fluids, and that there are four basic tissue types, may be a more significant departure from Artistotle's homoeomeres, and from Bichat's membranes and tissues, than commonly appreciated. The older concepts described these body parts as structural and functional parts of organs, whereas it is now commonplace to consider a tissue to be a grouping of similar cells with a variable amount of extracellular matrix. The development of the microscope as a useful tool in human anatomy shifted focus from tissues to cells and led to changes in the definition of tissue and the classification of tissues. Not all of these changes have been consistent with observable facts: many tissues contain diverse cell types, not all "connective tissues" are proper connective tissues, and some specialized tissues are not easily classified as subtypes of one of the four basic types. Here we propose corrective measures, including re-recognition of compound tissues, cataloging all adult human tissue types, and increasing the emphasis on function during the construction of a complete taxonomy of human adult tissues. Specific problems in the current scheme and a preliminary reclassification of human adult tissues are discussed.

Joseph von Gerlach-A Reminder of One of the Pioneers of Histochemistry on the Occasion of His 200th Birthday.

Joseph von Gerlach was an eminent German anatomist and pioneer of histology. He devised various techniques to assess the fine structure of tissues, most notably a procedure of staining histologic sections that marked the beginning of routine staining in histology. Gerlach was also one of the pioneers of microphotography.

Antecedents, development, adoption, and application of Duchenne's trocar for histopathologic studies of neuromuscular disorders in the nineteenth century.

Duchenne de Boulogne was one of the founders of clinical neurology. His name has been eponymically linked to the most common form of muscular dystrophy, originally described by him as pseudo-hypertrophic muscular paralysis or myo-sclerotic paralysis. Obtaining muscle biopsy specimens was essential to gain insight about the etiopathogenensis of the disease. Duchenne invented a novel instrument: l'emporte-pièce histologique, also known as "Duchenne's trocar," to perform muscle biopsies. Following Duchenne's design and instructions, a Parisian company, Charrière, constructed the first instrument probably in 1864. That instrument was essential for Duchenne's description of the histopathological abnormalities typical of pseudo-hypertrophic muscular paralysis. The innovative needle-biopsy technique enabled physicians to analyze the spectrum of pathological changes at varying stages of different neuromuscular diseases. Duchenne's trocar was a forerunner of several types of modern muscle-biopsy needles. His invention was instrumental in the development of the disciplines of muscle pathology and clinical myology.

Para una reconsideración del legado de Ramón y Cajal a las neurociencias / A Reconsideration of the legacy of Ramón y Cajal to the neurosciences

Entre 1887 y 1897 Santiago Ramón y Cajal realizó una serie de estudios micrográficos que jalonarían el debate acerca de la estructura y la fisiología del sistema nervioso al suministrar substrato empírico y guía heurística al marco teórico dentro del cual serían las mismas investigadas en lo sucesivo. El significado del trabajo realizado por Cajal en ese decenio no puede ponderarse sin un serio intento de establecer los pertinentes vínculos entre el mismo, sus antecedentes y su contexto contemporáneo. A tal fin, los apartados primero y segundo abordan el contexto científico en que Cajal elaborara en el periodo indicado la teoría neuronal y la ley de la polarización dinámica, prestando atención a planteamientos convergentes y divergentes de contemporáneos y antecesores. El tercero, por su parte, se dedica a la discusión del marco metodológico de la formulación de las señaladas aportaciones, soslayando recientes conatos de polémica historiográfica en torno a la paternidad de las mismas e incidiendo en que el núcleo del legado de Cajal no ha de buscarse en discusiones de esta naturaleza, sino en el amplio cuerpo de observaciones que recogiera y, muy particularmente, en la profusión de hipótesis mediante las cuales tratara de incardinarlo cabalmente en los marcos teóricos sancionados en ciencias biológicas

Between 1887 and 1897, Santiago Ramón y Cajal carried out a series of micrographic studies that would mark the debate about the structure and the physiology of the nervous system, establishing the theoretical framework for its study in the 20th century. The nature and meaning of the task undertaken by Cajal could not be fully weighed without a serious attempt to establish the pertinent links between such task, its antecedents and its contemporary context. To this end, the first and second sections address the scientific context in which, during the aforementioned period, Cajal elaborated the neuron doctrine and the dynamic polarization law, focusing on the convergent and divergent approaches of previous and contemporary researchers. The third section, on the other hand, is devoted to the discussion of the methodological framework of the formulation of the abovementioned contributions, avoiding recent attempts of historiographical controversy about its paternity and emphasizing that the core of Cajal’s legacy does not have to be sought in discussions of this nature, but in the wide body of observations he collected and, particularly, in the profusion of hypotheses he used in order to incardinate those contributions within the theoretical frameworks sanctioned in biological sciences

A comprehensive evaluation for the treatment of lupus nephritis.

Systemic lupus is the prototypic human autoimmune disease. It is a kaleidoscope of autoreactivities, with clear indications of both a genetic and environmental basis. Indeed, it is a disease that can manifest in virtually every tissue and organ and can also be found spontaneously in a number of animal species, including dogs, cats and horses. Moreover, there are multiple murine models of lupus, the first of which, New Zealand Black (NZB) mice, were discovered in 1959. Despite an enormous effort from scientists in multiple disciplines, the etiology of lupus remains elusive and the introduction of new therapies has been disappointing. Fortunately, significant advances have occurred to help patients through the general principles of internal medicine, including antibiotics, dialysis, and of course use of steroids and immunosuppressive agents. However, the magic bullet has yet to be discovered. One of the major causes of morbidity in lupus remains lupus nephritis and there has been significant effort and encouragement in understanding the pathogenesis, renal histologic classification, and use of therapeutic protocols to induce and sustain remission of lupus nephritis. Indeed, the first use of evidence-based clinical trials in lupus was initiated by Dr. Alfred D. Steinberg at NIH in pioneering studies involving either oral or intravenous pulses of cyclophosphamide, azathioprine or corticosteroids alone and/or some combination. Cyclophosphamide intravenously proved to be superior and the use of cyclophosphamide in combination with methylprednisolone remained the standard protocol for the treatment of lupus nephritis for decades. Although alternative therapies have been introduced, including mycophenolate mofetil, the use of therapies first pioneered at NIH may still be considered standard of care in the appropriate indications. More targeted therapies are much desired. In this review we provide a comprehensive overview of lupus nephritis and the evolution of clinical treatments.

Discovering the structure of nerve tissue: Part 3: From Jan Evangelista Purkyne to Ludwig Mauthner.

The previous works of Purkyne, Valentin, and Remak showed that the central and peripheral nervous systems contained not only nerve fibers but also cellular elements. The use of microscopes and new fixation techniques enabled them to accurately obtain data on the structure of nerve tissue and consequently in many European universities microscopes started to become widely used in histological and morphological studies. The present review summarizes important discoveries concerning the structure of neural tissue, mostly from vertebrates, during the period from 1838 to 1865. This review describes the discoveries of famous as well as less well-known scholars of the time, who contributed significantly to current understandings about the structure of neural tissue. The period is characterized by the first descriptions of different types of nerve cells and the first attempts of a cytoarchitectonic description of the spinal cord and brain. During the same time, the concept of a neuroglial tissue was introduced, first as a tissue for "gluing" nerve fibers, cells, and blood capillaries into one unit, but later some glial cells were described for the first time. Questions arose as to whether or not cells in ganglia and the central nervous system had the same morphological and functional properties, and whether nerve fibers and cell bodies were interconnected. Microscopic techniques started to be used for the examination of physiological as well as pathological nerve tissues. The overall state of knowledge was just a step away from the emergence of the concept of neurons and glial cells.

Discovering the Structure of Nerve Tissue: Part 2: Gabriel Valentin, Robert Remak, and Jan Evangelista Purkyne.

During the 1830s, the use of improved microscopic techniques together with new histological methods, including tissue fixation, allowed more precise data to be obtained concerning the structure of nerve tissue of animals as well as humans. The present article, based on the translations of original texts never before published, brings together for the first time the discoveries of famous scholars Gustav Valentin, Robert Remak, and Jan Evangelista Purkyne, who made their significant discoveries in the field of neuroscience almost simultaneously and shows how their findings affected each other. In addition, this article also contains digitally remastered and reconstructed figures published in the original works of Valentin, Remak, and Purkyne and they are displayed for the first time in high quality. Although the fundamental discoveries of these famous scholars did not imply the discovery of nerve cells as we know them today, they were certainly a very important basis for further research of many other eminent scholars during the second half of the nineteenth century.

Comments on the history of the Biological Stain Commission, Inc.

Nearly 89 years ago, the Society of American Bacteriologists appointed Dr. Harold Conn to form a committee to standardize the stains and dyes used in biological and medical research and diagnosis. Dr. Conn's efforts led to formation of the Committee on the Standardization of Biological Stains, later incorporated as the Biological Stain Commission. This article traces some of the events and factors that shaped the course of the Biological Stain Commission into its current form and functions. Its principal function is to ensure that the biological and medical communities have access to high quality, dependable and consistent biological dyes and stains.

Abelardo Gallego (1879-1930) and his contributions to histotechnology: the Gallego stains.

The Gallego general tissue stain is used in histology and histopathology and stains beautifully connective tissue, in which all nuclei are stained in magenta red, epithelial cytoplasm in red-yellow, connective tissue is stained in brilliant green, muscle in olive green, and keratinized epithelium and blood in grass green. There is also Gallego's method for differential staining of elastic tissue that enables a complete differentiation between elastic and collagenous connective tissue. The elastic tissue is stained in brilliant fuschin red, while collagen is stained in brilliant green. Abelardo Gallego was born in Spain on September 10, 1879. He was appointed as professor of Pharmacology and Therapeutics at the Faculty of Veterinary Medicine at the University of Santiago de Compostela, Spain, and in 1921 became full-time professor of Histology and Pathology in Madrid supported by Ramón y Cajal. Gallego conducted extensive research into veterinary pathology. Don Abelardo was a quiet, reserved, but friendly, sensitive, optimistic and persistent person. Weakened by a bout of bronchitis, Gallego died aged 51 on February 3, 1930, and was buried at the Almudena Cemetery, in Madrid. Gallego was one of the most outstanding scientists of Spanish veterinary medicine and some of his achievements are reviewed.

The growth cone as seen through Cajal's original histological preparations and publications.

During the development of the nervous system, each neuron must contact its appropriate target cell in order to establish its specific connections. More than a century ago, Ramon y Cajal discovered an amoeboid-like structure at the end of the axon of developing nerve cells. He called this structure the growth cone [cono de crecimiento] and he proposed that this structure was guided towards its target tissue by chemical substances secreted by the different cells that line its course. We have reviewed the discovery of the growth cone by Cajal using his original publications, his original scientific drawings, and by studying his histological preparations conserved at the "Instituto Cajal" (Madrid, Spain).(1) We found a very good correlation between the structure of the growth cone in the Golgi-impregnated and reduced silver-nitrate-stained material used by Cajal, and that which is revealed with present-day methods. Finally, Cajal's view of the function of the growth cone and his chemotactic hypothesis will also be considered in the light of present-day knowledge.

Los "cuadernos de campo" y esbozos histológicos en la obra de Salvador Gil Vernet / Field notebooks and histologic drawings in the work of Salvador Gil Vernet

Trabajo basado en 11 libretas de campo, con sus anotaciones y descripciones de las preparaciones anatómicas macro y microscópicas. Existe además un cuaderno con varios dibujos hechos a mano y a lápiz de mina negra, que reproducen la anatomía microscópica del cuello; además cinco láminas de formato 60x40 cm. de dibujos histológicos, varias preparaciones histológicas, así como algunos papeles de carta con el membrete de Don Salvador en sus distintas facetas institucionales (AU)

Our work is based on 11 field notebooks with his notes and descriptions of macroscopic and microscopic anatomic preparations. There is also one notebook with several handmade drawings on black lead pencil, reproducing the microscopic anatomy of the bladder neck; there are also five 60 x 40 cm prints with histologic drawings, several histologic preparations, as well as several letter papers with Dr. Salvador's letterhead in his various institutional aspects (AU)

Diagnostic value of micro-CT in comparison with histology in the qualitative assessment of historical human postcranial bone pathologies.

Micro-computed tomography (muCT) is of great interest for palaeopathological examination because it is less invasive than histology. This study evaluates the diagnostic value of muCT for postcranial macerated bones. We investigated five specimens (osteomyelitis, tuberculosis, trauma, osteosarcoma and hypertrophic osteoarthropathy) of a pathology reference series by muCT and polarised light microscopy. The 3D muCT images allow an easy orientation within the specimen. Surface structures, thickness, continuity of the cortex and number, thickness and orientation of the trabeculae can be evaluated. The high number of muCT slices helps to choose the most interesting areas for further investigations. Grey value images display the degree of mineralisation. Yet, the differentiation between woven and lamellar bone is only possible using polarised light microscopy. muCT is a tool of high value for the examination of postcranial bone disorders. It cannot replace histological examinations completely because it cannot assess the bone quality (woven or lamellar). For the choice of the optimal location where slices for the microscopic investigation are later cut in heterogeneous samples, muCT is very useful. Therefore, we suggest performing the muCT examination first, followed by histology if necessary.

[Historical review of development of neuro-historogical techniques and three-dimensional reconstruction of individual neurons].

The image of neuron proposed by Barker in 1899 is until now useful. However this image could be said to be only a schema based on the data obtained by various histological techniques developed in the latter half of the nineteenth century. Although thereafter many careful observations on neuronal architecture have been made, much still remains to be done for revealing their true geometry. In our histological analysis with Golgi-stained materials in the cat, it was found that the reflecting illumination showed the somal surface and its relationship with the dendrites in clear relief. With this method it was possible to develop a new approach for photogrammetric representation of the neuronal soma as well as for following the total course of dendrites in successive serial sections that had been cut off by the microtome knife. This has provided a means for estimating precisely the dimensions of the neuron. In addition, by means of the intra-axonally injection of HRP in cats, the intramedullary course of physiologically identified afferent fibers originating from various muscles in lumbosacral region was also reconstructed three-dimensionally from serial sections. The results thus obtained revealed that the collaterals belonging to groups Ia, Ib and II fibers of the muscles examined showed some typical differences in their courses and in their terminations in the gray matter. The results of extra-cellular injection of BDA (Sato F. et al., 2000) into the Nucl. subthalamicus in monkeys also cited as this sort of work. It should be emphasized that, whether classic manual method or more effective modern techniques are used, three-dimensional reconstruction is the most important factor for studying the comlete axonal geometry of individual neurons, of which effects may be said, at least at present, to be still methodologically incomplete.

Evolution of the silver and gold stains in neurohistology.

Scientific investigations depend on the reliability of the observations that can be made. This reliability is determined in part by the understanding of the techniques and technology used to make the observations. The limitations and the strengths of the methodology and the equipment used must be evaluated thoroughly. The extent to which this is and has been the case for the use of the metal based stains in neuroscience is the subject of this paper. I evaluate the metallic stains used for neuroscience from several perspectives. I review briefly the state of neurohistology prior to its "golden years," 1870-1910. Then I trace the development of the silver based stains used for neurohistology. I wanted to discuss the reasoning used by the originators of the silver based techniques in developing their specific procedures, but discovered that while procedures may be published, the methods and ideas used to arrive at the final procedures are not usually described in published work.

Central projections of the vestibular nerve: a review and single fiber study in the Mongolian gerbil.

The primary purpose of this article is to review the anatomy of central projections of the vestibular nerve in amniotes. We also report primary data regarding the central projections of individual horseradish peroxidase (HRP)-filled afferents innervating the saccular macula, horizontal semicircular canal ampulla, and anterior semicircular canal ampulla of the gerbil. In total, 52 characterized primary vestibular afferent axons were intraaxonally injected with HRP and traced centrally to terminations. Lateral and anterior canal afferents projected most heavily to the medial and superior vestibular nuclei. Saccular afferents projected strongly to the spinal vestibular nucleus, weakly to other vestibular nuclei, to the interstitial nucleus of the eighth nerve, the cochlear nuclei, the external cuneate nucleus, and nucleus y. The current findings reinforce the preponderance of literature. The central distribution of vestibular afferents is not homogeneous. We review the distribution of primary afferent terminations described for a variety of mammalian and avian species. The tremendous overlap of the distributions of terminals from the specific vestibular nerve branches with one another and with other sensory inputs provides a rich environment for sensory integration.