Von Gersdorff Research Articles

Locating the Hand and Sense of Touch in Sixteenth-Century Surgical Writings of Ambrose Paré and Hans von Gersdorff

Objective: This article offers two case studies of sixteenth-century surgical approaches to the hand and definitions of the sense of touch in works by Frenchman Ambrose Paré and German Hans von Gersdorff. 
 Method: Through comparative analysis, this article studies references to and treatments of hand ailments in the sixteenth-century surgical manuals printed by Ambrose Paré and Hans von Gersdorff. Research was conducted between 2012-2014, updated in 2023, and focuses specifically on digital versions of Ambrose Paré’s vernacular French “Ten Books of Surgery” collected in his Opera Omnia (1575) held at the Bibliothèque nationale de France and Hans von Gersdorff’s Feldtbuch der Wundartzney (1517) held at the University of Heidelberg, Germany.
 Results: The human hand in the sixteenth century was both a natural and symbolic object whereby the hand offered individuals the immediacy of the sense of touch, established the boundary between those that exercised their hands (manual practitioners), and those who abstained from manual labor in favor of intellectual pursuits (theoreticians). Through discussions of limb amputation, Ambrose Paré located the sense of touch in the soul and not an amputated limb. In contrast, Hans von Gersdorff located the sense of touch in the hand itself, which retained a special power after amputation. 
 Conclusion: The increased reliance on dissection and anatomy, visual arts, personal experience, and publishing in sixteenth-century Europe offers historians a series of divergent surgical rituals and interpretations of the body, specifically the hand and sense of touch. Contemporary theories of embodied cognition mirror the problem of the location of the sense of touch in the mind or in the organ itself found in Paré and Gersorff’s writings.

Images & Color: The Strasbourg Printer Johann Schott (1477–1548) and His Circle

Abstract While most Renaissance scholars working on compendia of learning, geography, surgery, legal history, art history, the Reformation, and botany will be familiar with the name of Johann Schott, few have appreciated the range and impact of the Strasbourg printer’s publications. Here I discuss a handful among the over two hundred books and other materials he printed: Gregor Reisch’s Margarita Philosophica; the edition of Ptolemy’s Geographia with Waldseemüller’s maps; Hans von Gersdorff, Feldtbuch der Wundarzney; and – the main focus this essay – Herbarum vivae eicones, with figures by Hans Weiditz and text by Otto Brunfels. Schott can be seen as an architect or active agent of his publications; his innovative use of images and color can be seen as having progressively developed from his early prints to his celebrated herbal.

Niezrealizowane projekty odbudowy kościoła w Oruni autorstwa gdańskiego architekta miejskiego Carla Samuela Helda

This article discusses widely unknown designs of the Evangelical church in the village of Orunia near Gdańsk from 1816–1819. The concepts preserved in the State Archive in Gdańsk contain as many as eight variants of the reconstruction of the meeting house destroyed during a siege in 1813. The author of these concepts was the contemporary city architect Carl Samuel Held. As a student of Carl Gotthard Langhans (1732–1808), one of the greatest Prussian architects of that time, Held consistently used classicist forms throughout his body of work. His first two designs for the reconstruction of the church in question were in line with the so-called revolutionary classicism. The following six neo-Gothic variants constituted a formal exception in his oeuvre. Moreover, the case of the Orunia church was the only time he ever attempted to design a sacral building. The clumsiness in the use of neo-Gothic forms, as well as the inability to fit into the assumed financial framework contributed to the rejection of Held’s designs. Eventually, the project by August von Gersdorff verified by the head of the Higher Construction Deputy Karl Friedrich Schinkel was the one that was implemented. The construction was completed in 1823. The forms used in the building exhibit inspiration drawn from the Teutonic castle in Malbork. The prime mover behind their use was the Oberpräsident of the Province of West Prussia Theodor von Schön, promoter of the restoration work at the castle. The church in Orunia is the first case of a building with neo-Gothic features in Gdańsk and its area, as well as the first construction with forms intentionally referring to the Malbork Castle, a landmark symbolizing the essence of Germanity.

Convergent Evolution of Mucosal Immune Responses at the Buccal Cavity of Teleost Fish.

SummaryThe buccal mucosa (BM) is a critical first line of defense in terrestrial animals. To gain further insights into the evolutionary origins and primordial roles of BM in teleosts here we show that rainbow trout, a teleost fish, contains a diffuse mucosal associated lymphoid tissue (MALT) within its buccal cavity. Upon parasite infection, a fish immunoglobulin specialized in mucosal immunity (sIgT) was induced to a high degree, and parasite-specific sIgT responses were mainly detected in the buccal mucus. Moreover, we show that the trout buccal microbiota is prevalently coated with sIgT. Overall our findings revealed that the MALT is present in the BM of a non-tetrapod species. As fish IgT and mucus-producing cells are evolutionarily unrelated to mammalian IgA and salivary glands, respectively, our findings indicate that mucosal immune responses in the BM of teleost fish and tetrapods evolved through a process of convergent evolution.

Neuronal excitatory amino acid transporter EAAT3: Emerging functions in health and disease

Plasma membrane neurotransmitter transporters maintain extracellular concentrations of neurotransmitters by facilitating transport into the cytosol. This regulation of extracellular neurotransmitters limits binding to receptors and activation of downstream signaling pathways. In addition to this critical function, transporters modulate neuronal activity via direct gating of transporter-associated ion channels and indirectly through trafficking of transporters to and from the plasma membrane. These functions are dependent on diverse expression patterns and levels of the transporters throughout the brain. This diversity is highlighted within the excitatory amino acid transporter family, which consists of five excitatory amino acid transporters found in the mammalian central nervous system (CNS). EAAT1 (GLAST) and EAAT2 (GLT-1) are primarily expressed in astrocytes while EAAT3 expression is mainly observed in many neurons throughout the brain (Holmseth et al., 2012). In contrast, EAAT4 is most prominently expressed in cerebellar Purkinje neurons and EAAT5 is exclusively found in the retina. In general, the astroglial transporters are highly expressed in the brain; EAAT2 is the most abundant, followed by EAAT1 with approximately a 4-fold lower expression (Holmseth et al., 2012). High expression levels of these glial transporters are consistent with their role in glutamate clearance (Lehre and Danbolt, 1998; Rothstein et al., 1996; Tanaka et al., 1997). The role of the neuronal transporter EAAT3 in brain has been more difficult to elucidate. Levels of EAAT3 are approximately 100-fold lower than EAAT2 (Holmseth et al., 2012) but EAAT3 expression is observed throughout the CNS, with enriched expression in the cerebral cortex, hippocampus, cerebellum and basal ganglia (Rothstein et al., 1994; Shashidharan et al., 1997). Given the lack of selective EAAT3 inhibitors, studies have relied on EAAT3 transporters expressed in various cells and endogenous transporters expressed in cultured hippocampal neurons (Diamond and Jahr, 1997; Grewer et al., 2000; Wadiche et al., 1995b), as well as EAAT3 knockout mice (Scimemi et al., 2009) to dertmine the physiological functions of EAAT3. These studies determined that the time course of glutamate in the synaptic cleft is a function of the binding of glutamate to EAATs and that transport of glutamate does not significantly contribute to the amplitude or kinetics of synaptic responses due to the relatively slow transport cycle (Diamond and Jahr, 1997; Tong and Jahr, 1994; Wadiche and von Gersdorff, 2006). Interestingly, EAAT3 knockout mice exhibit few behavioral deficits (Peghini et al., 1997), and antisense oligonucleotide knockdown in the striatum results in minimal elevation of extracellular glutamate levels or neurodegeneration, in contrast to knockdown of EAATs 1 and 2 (Rothstein et al., 1996). The lack of neurodegeneration is particularly surprising given that EAAT3 also serves as a cysteine transporter (Aoyama et al., 2006; Watts et al., 2014; Zerangue and Kavanaugh, 1996). Cysteine is the rate-limiting substrate for the synthesis of the antioxidant glutathione and its extracellular depletion is hypothesized to contribute to neurodegeneration. EAAT3 is also the dominant glutamate transporter in the intestines and provides nutrient absorption from the diet (Hu et al., 2018), but knockout animals appear to grow at a comparable rate to their litter mates (Peghini et al., 1997). The most remarkable initial observation from EAAT3 knockout mice was aminoaciduria due to the absence of EAAT3 in the kidneys (Peghini et al., 1997). The reported lack of overt behavioral abnormalities in the EAAT3 knockout mice suggest that either EAAT3 is not integral to regulation of glutamatergic signaling in the brain or that substantial developmental compensatory changes are induced in these mice. Human genetic studies and constitutive deletion mouse models have now provided evidence that EAAT3 has important roles in regulating neuronal signaling.

Calcium channels for endocytosis.

Calcium channels for endocytosis.

Use of Advanced Bleeding Control Mechanisms in Athletic Training: A Shift in the Thought Process of Prehospital Care—Part 1: Tourniquets

Two other competencies(Table 1), although not necessarily new to the list ofimmediate emergency management care skills, do requirefurther examination based on the current available scienceand standard of care in prehospital medicine. The purposeof this column is to provide athletic training educators(ATE) with evidence regarding the use of tourniquets in theprehospital setting as well as to be a resource on how toteach the management of external hemorrhage usingtourniquets.Trauma resulting in disruption of soft tissue is classified asan open or closed wound, and any significant loss ofintravascular volume may lead sequentially to hemodynam-ic instability, decreased tissue perfusion, cellular hypoxia,organ damage, and death.

Calcium-Dependent PKC Isoforms Have Specialized Roles in Short-Term Synaptic Plasticity

Posttetanic potentiation (PTP) is a widely observed form of short-term plasticity lasting for tens of seconds after high-frequency stimulation. Here we show that although protein kinase C (PKC) mediates PTP at the calyx of Held synapse in the auditory brainstem before and after hearing onset, PTP is produced primarily by an increased probability of release (p) before hearing onset, and by an increased readily releasable pool of vesicles (RRP) thereafter. We find that these mechanistic differences, which have distinct functional consequences, reflect unexpected differential actions of closely related calcium-dependent PKC isoforms. Prior to hearing onset, when PKCγ and PKCβ are both present, PKCγ mediates PTP by increasing p and partially suppressing PKCβ actions. After hearing onset, PKCγ is absent and PKCβ produces PTP by increasing RRP. In hearing animals, virally expressed PKCγ overrides PKCβ to produce PTP by increasing p. Thus, two similar PKC isoforms mediate PTP in distinctly different ways.

Art and science in the Renaissance: the case of Walther Hermann Ryff.

Few moments in mankind’s history have seen such an impressive cultural revolution as the one that occurred during the Renaissance. An entirely new concept of man emerged, and the philosophical principles of Humanism overcame the old ideas and ideals of the Medieval period. Besides the well-celebrated achievements in the fields of architecture, figurative arts, literature, and philosophy, science also presented important innovations, particularly in medical studies, which were strengthened by the Renaissance concepts of the centrality of humanity and the rejection of dogmatic knowledge. Medical schools had been flourishing throughout Europe since the 11th century, and a new figure was acquiring social and cultural relevance: The surgeon. In previous centuries, surgeons were considered lower level practitioners, since their profession was regarded as a form of craft. The emerging knowledge about human anatomy, partially due to the studies of enlightened artists such as Leonardo da Vinci and Michelangelo, brought a new awareness about the role of surgical treatments. One of the most fascinating aspects of surgery during those times was the fact that it was performed by people representing the Renaissance ideal of polymath— people not only interested in one specific field, but endowed with a creative and inquisitive spirit so powerful that they were often also poets, artists, mathematicians, naturalists, and more. Although surgery had ascended beyond a mere craft, the profession still needed to find its own voice, and the invention of printing offered the chance to spread this new knowledge. The illustrations contained in those precious books made them works of art. As such, surgical knowledge was conveyed through art during the Renaissance. Today, these documents are admired as artwork, but they also can help us reconstruct Renaissance everyday life and trace the evolution of surgical techniques through time. In this column, we focus on one of these amazing books, Grossen Chirurgie (Great Surgery), by the German surgeon Walther Hermann Ryff. The book is considered both a masterpiece of Renaissance printing and among the most accurate sources to understand current concepts of traumatology during the Renaissance.

A History of Depressed Skull Fractures from Ancient Times to 1800

The story of managing depressed fractures illustrates how knowledge of proven value does not always get handed down. Celsus was the first to describe sensible management for depressed fractures. As he wrote in Latin this was forgotten. Galen’s Greek writings survived forming the basis of management until the sixteenth century. In 1517, Hans von Gersdorff published a formidable illustrated surgical text. One illustration depicts an instrument for elevating depressed bone fragments. It looked dramatic but could not work and its defects were finally defined in the eighteenth century. Ambroise Paré used a bone punch just as we do today, but no later surgeon mentions this, though the instrument was well known. Elements of chance, fashion, emotionally powerful illustrations, and perhaps stubbornness had a profound effect on management delaying rational treatment for centuries.

Synaptic Ribbons Influence the Size and Frequency of Miniature-like Evoked Postsynaptic Currents

Nonspiking cells of several sensory systems respond to stimuli with graded changes in neurotransmitter release and possess specialized synaptic ribbons. Here, we show that manipulations to synaptic ribbons caused dramatic effects on mEPSC-like (mlEPSC) amplitude and frequency. Damage to rod-bipolar cell ribbons using fluorophore-assisted light inactivation resulted in the immediate reduction of mlEPSC amplitude and frequency, whereas the first evoked response after damage remained largely intact. The reduction in amplitude could not be recovered by increasing release frequency after ribbon damage. In parallel experiments, we looked at mlEPSCs from cones of hibernating ground squirrels, which exhibit dramatically smaller ribbons than awake animals. Fewer and smaller mlEPSCs were observed postsynaptic to cones from hibernating animals, although depolarized cones were able to generate larger mlEPSCs. Our results indicate that ribbon size may influence mlEPSC frequency and support a role for ribbons in coordinating multivesicular release.

Surgeon or Lexicographer? The Latin-German Glossaries in Addendum to Hans von Gersdorff's Feldtbuch der Wundarzney

At the end of his Feldtbuch der Wundarzney (Strasburg / Schott 1517), Hans von Gersdorff inserts three Latin-German glossaries (anatomy, pathology and medical herbs). It’s the first time a printed German surgical handbook includes a glossary, thus explicitly recognizing the existence of a potential understanding problem posed by the abundance of classical terminology in these specific semantic fields. In this study, the structure and organization of these three glossaries are analysed, paying particular attention not only to the selection of the Latin headwords and the choice of the vernacular rendering(s) of the Latin headwords, but also to their relation to the surgical technical terminology employed by the author in the treatise itself. In this way, it is possible to ascertain whether this, in nuce, specialized dictionary had been conceived as simply instrumental to the didactic purposes of the handbook, or aimed at pursuing a more universal goal, in the same way as today’s technical dictionaries.

Spikes in Mammalian Bipolar Cells Support Temporal Layering of the Inner Retina

In the mammalian retina, 10-12 different cone bipolar cell (BC) types decompose the photoreceptor signal into parallel channels, providing the basis for the functional diversity of retinal ganglion cells (RGCs). BCs differing in their temporal properties appear to project to different strata of the retina's inner synaptic layer, based on somatic recordings of BCs and excitatory synaptic currents measured in RGCs. However, postsynaptic currents in RGCs are influenced by dendritic morphology and receptor types, and the BC signal can be transformed at the axon terminals both through interactions with amacrine cells and through the generation of all-or-nothing spikes. Therefore, the temporal properties of the BC output have not been analyzed systematically across different types of mammalian BCs. We recorded calcium signals directly within axon terminals using two-photon imaging and show that BCs can be divided into ≥eight functional clusters. The temporal properties of the BC output were directly reflected in their anatomical organization within the retina's inner synaptic layer: faster cells stratified closer to the border between ON and OFF sublamina. Moreover, ≥three fastest groups generated clear all-or-nothing spikes. Therefore, the systematic projection pattern of BCs provides distinct temporal "building blocks" for the feature extracting circuits of the inner retina.

Activation of metabotropic glutamate receptors improves the accuracy of coincidence detection by presynaptic mechanisms in the nucleus laminaris of the chick

Interaural time difference (ITD) is a major cue for localizing a sound source and is processed in the nucleus laminaris (NL) in birds. Coincidence detection (CD) is a crucial step for processing ITD and critically depends on the size and time course of excitatory postsynaptic potentials (EPSPs). Here, we investigated a role of metabotropic glutamate receptors (mGluRs) in the regulation of EPSP amplitude and CD in the NL of chicks. A non-specific agonist of mGluRs ((±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid; t-ACPD) reduced the amplitude and extent of depression of excitatory postsynaptic currents (EPSCs) during a stimulus train, while the paired pulse ratio and coefficient of variation of EPSC amplitude were increased. In contrast, the amplitudes of spontaneous EPSCs were not affected, but the frequency was reduced. Thus, the effects of t-ACPD were presynaptic and reduced the release of neurotransmitter from terminals in the NL. Expression of group II mGluRs was graded along the tonotopic axis and was stronger towards the low frequency region in the NL. Both group II (DCG-IV) and group III (l-AP4) specific agonists reduced EPSC amplitude by presynaptic mechanisms, and the reduction was larger in the low frequency region; however, we could not find any effects of group I-specific agonists on EPSCs. The reduced EPSP amplitude in DCG-IV improved CD. A specific antagonist of group II mGluRs (LY341495) increased the amplitude of both EPSCs and EPSPs and enhanced the depression during a stimulus train, indicating constitutive activation of mGluRs in the NL. These observations indicate that mGluRs may work as autoreceptors and regulate EPSP size to improve CD in the NL.

Activity-Induced Long-Term Potentiation of Excitatory Synapses in Developing Zebrafish Retina In Vivo

Neural activity-induced long-term potentiation (LTP) of synaptic transmission is believed to be one of the cellular mechanisms underlying experience-dependent developmental refinement of neural circuits. Although it is well established that visual experience and neural activity are critical for the refinement of retinal circuits, whether and how LTP occurs in the retina remain unknown. Using in vivo perforated whole-cell recording and two-photon calcium imaging, we find that both repeated electrical and visual stimulations can induce LTP at excitatory synapses formed by bipolar cells on retinal ganglion cells in larval but not juvenile zebrafish. LTP induction requires the activation of postsynaptic N-methyl-D-aspartate receptors, and its expression involves arachidonic acid-dependent presynaptic changes in calcium dynamics and neurotransmitter release. Physiologically, both electrical and visual stimulation-induced LTP can enhance visual responses of retinal ganglion cells. Thus, LTP exists in developing retinae with a presynaptic locus and may serve for visual experience-dependent refinement of retinal circuits.

Coupled Control of Desensitization and Gating by the Ligand Binding Domain of Glutamate Receptors

The kinetics of ligand gated ion channels are tuned to permit diverse roles in cellular signaling. To follow high-frequency excitatory synaptic input, postsynaptic AMPA-type glutamate receptors must recover rapidly from desensitization. Chimeras between AMPA and the related kainate receptors demonstrate that the ligand binding domains alone control the lifetime of the desensitized state. Mutation of nonconserved amino acids in the lower lobe (domain 2) of the ligand binding domain conferred slow recovery from desensitization on AMPA receptors, and fast recovery on kainate receptors. Single-channel recordings and a correlation between the rate of deactivation and the rate of recovery across panels of mutant receptors revealed that domain 2 also controls ion channel gating. Our results demonstrate that the same mechanism that ensures fast recovery also sharpens the response of AMPA channels to synaptically released glutamate.

Voltage-Dependent Calcium Channels at the Plasma Membrane, but Not Vesicular Channels, Couple Exocytosis to Endocytosis

Although calcium influx triggers endocytosis at many synapses and non-neuronal secretory cells, the identity of the calcium channel is unclear. The plasma membrane voltage-dependent calcium channel (VDCC) is a candidate, and it was recently proposed that exocytosis transiently inserts vesicular calcium channels at the plasma membrane, thus triggering endocytosis and coupling it to exocytosis, a mechanism suggested to be conserved from sea urchin to human. Here, we report that the vesicular membrane, when inserted into the plasma membrane upon exocytosis, does not generate a calcium current or calcium increase at a mammalian nerve terminal. Instead, VDCCs at the plasma membrane, including the P/Q-type, provide the calcium influx to trigger rapid and slow endocytosis and, thus, couple endocytosis to exocytosis. These findings call for reconsideration of the vesicular calcium channel hypothesis. They are likely to apply to many synapses and non-neuronal cells in which VDCCs control exocytosis, and exocytosis is coupled to endocytosis.

Disruption of Smad4 impairs TGF-β/Smad3 and Smad7 transcriptional regulation during renal inflammation and fibrosis in vivo and in vitro

The mechanism by which TGF-β regulates renal inflammation and fibrosis is largely unclear; however, it is well accepted that its biological effects are mediated through Smad2 and Smad3 phosphorylation. Following activation, these Smads form heteromeric complex with Smad4 and translocate into the nucleus to bind and regulate the expression of target genes. Here we studied the roles of Smad4 to regulate TGF-β signaling in a mouse model of unilateral ureteral obstruction using conditional Smad4 knockout mice and in isolated Smad4 mutant macrophages and fibroblasts. Disruption of Smad4 significantly enhanced renal inflammation as evidenced by a greater CD45(+) leukocyte and F4/80(+) macrophage infiltration and upregulation of IL-1β, TNF-α, MCP-1, and ICAM-1 in the obstructed kidney and in IL-1β-stimulated macrophages. In contrast, deletion of Smad4 inhibited renal fibrosis and TGF-β1-induced collagen I expression by fibroblasts. Further studies showed that the loss of Smad4 repressed Smad7 transcription, leading to a loss of functional protein. This, in turn, inhibited IκBα expression but enhanced NF-κB activation, thereby promoting renal inflammation. Interestingly, deletion of Smad4 influenced Smad3-mediated promoter activities and the binding of Smad3 to the COL1A2 promoter, but not Smad3 phosphorylation and nuclear translocation, thereby inhibiting the fibrotic response. Thus, Smad4 may be a key regulator for the diverse roles of TGF-β1 in inflammation and fibrogenesis by interacting with Smad7 and Smad3 to influence their transcriptional activities in renal inflammation and fibrosis.

Calcium-Dependent Synaptic Vesicle Trafficking Underlies Indefatigable Release at the Hair Cell Afferent Fiber Synapse

Sensory hair cell ribbon synapses respond to gradedstimulation in a linear, indefatigable manner, requiring that vesicle trafficking to synapses be rapid and nonrate-limiting. Real-time monitoring of vesicle fusion identified two release components. The first was saturable with both release rate and magnitude varying linearly with Ca(2+), however the magnitude was too small to account for sustained afferent firing rates. A second superlinear release component required recruitment, in a Ca(2+)-dependent manner, of vesicles not in the immediate vicinity of the synapse. The superlinear component had a constant rate with its onset varying with Ca(2+) load. High-speed Ca(2+) imaging revealed a nonlinear increase in internal Ca(2+) correlating with the superlinear capacitance change, implicating release of stored Ca(2+) in driving vesicle recruitment. These data, supported by a mass action model, suggest sustained release at hair cell afferent fiber synapse is dictated by Ca(2+)-dependent vesicle recruitment from a reserve pool.

V-ATPase Membrane Sector Associates with Synaptobrevin to Modulate Neurotransmitter Release

Acidification of synaptic vesicles by the vacuolar proton ATPase is essential for loading with neurotransmitter. Debated findings have suggested that V-ATPase membrane domain (V0) also contributes to Ca(2+)-dependent transmitter release via a direct role in vesicle membrane fusion, but the underlying mechanisms remain obscure. We now report a direct interaction between V0 c-subunit and the v-SNARE synaptobrevin, constituting a molecular link between the V-ATPase and SNARE-mediated fusion. Interaction domains were mapped to the membrane-proximal domain of VAMP2 and the cytosolic 3.4 loop of c-subunit. Acute perturbation of this interaction with c-subunit 3.4 loop peptides did not affect synaptic vesicle proton pump activity, but induced a substantial decrease in neurotransmitter release probability, inhibiting glutamatergic as well as cholinergic transmission in cortical slices and cultured sympathetic neurons, respectively. Thus, V-ATPase may ensure two independent functions: proton transport by a fully assembled V-ATPase and a role in SNARE-dependent exocytosis by the V0 sector.