Scanning electron microscopy of the surfaces of hamster embryo cells transformed by herpes simplex virus.

The surfaces of normal hamster embryo fibroblast (HEF) cells were examined by scanning electron microscopy. Surface characteristics of HEF cells were compared to those of cells derived from a primary tumor induced in hamsters following s.c. inoculation of herpes simplex virus type 1-transformed HEF cells (14-012-8-1) and to the surfaces of cells derived from a metastatic tumor to the lung induced by the same cells. The most obvious difference in the surface characteristics of the examined cells was the morphology of the microvilli. In the few HEF cells that possessed microvilli, the distribution was uneven, and the lengths of the microvilli and the filopodia were variable. However, the surfaces of both tumor cell lines showed large numbers of microvilli which were evenly distributed over the surface of the cells, giving an almost "hairy" appearance. Long filopodia were occasionally observed on the surface of the primary tumor cell line and on the cell line derived from the metastatic tumor. Ruffles and blebs were occasionally observed on HEF cells and on the primary tumor cells but were not seen on the cells of the metastatic tumor.

Diabetes mellitus in the guinea pig.

Spontaneous diabetes mellitus has been documented in a colony of guinea pigs. The contagious nature of the disease has been verified, but the nature of the infectious agent is not known. Animals from the original colony or animals exposed to the colony with normal glucose tolerance tests (GTT) became diabetic, as evidenced by elevated one- and four-hour GTT values, and in most cases have significant glycosuria. The severity of pathologic changes in the pancreatic islets parallel, in general, the severity of the clinical symptoms (glycosuria and abnormal GTT). Those animals with severe glycosuria and elevated FBS as well as one- and four-hour GTT values had the most pronounced degranulation and most prominent cytoplasmic inclusions in islet B cells. The severity of scarring in the islets can be correlated with the duration of the overt diabetic state. The other clinical parameters of note were elevated serum triglycerides, normal serum but elevated aortic cholesterol, and absence of ketonemia or ketonuria. The reproductive capacity of diabetic females was compromised. While the clinical manifestations are mild or variable, the presence of significant islet pathology is reminiscent of human juvenile diabetes mellitus. These findings lend support to the concept that infectious and/or immune mechanisms could be operative in the etiology and pathogenesis of human diabetes mellitus.

Clinical Informatics Fellowship Programs: In Search of a Viable Financial Model: An open letter to the Centers for Medicare and Medicaid Services.

In the US, the new subspecialty of Clinical Informatics focuses on systems-level improvements in care delivery through the use of health information technology (HIT), data analytics, clinical decision support, data visualization and related tools. Clinical informatics is one of the first subspecialties in medicine open to physicians trained in any primary specialty. Clinical Informatics benefits patients and payers such as Medicare and Medicaid through its potential to reduce errors, increase safety, reduce costs, and improve care coordination and efficiency. Even though Clinical Informatics benefits patients and payers, because GME funding from the Centers for Medicare and Medicaid Services (CMS) has not grown at the same rate as training programs, the majority of the cost of training new Clinical Informaticians is currently paid by academic health science centers, which is unsustainable. To maintain the value of HIT investments by the government and health care organizations, we must train sufficient leaders in Clinical Informatics. In the best interest of patients, payers, and the US society, it is therefore critical to find viable financial models for Clinical Informatics fellowship programs. To support the development of adequate training programs in Clinical Informatics, we request that the Centers for Medicare and Medicaid Services (CMS) issue clarifying guidance that would allow accredited ACGME institutions to bill for clinical services delivered by fellows at the fellowship program site within their primary specialty.

Neural-epithelial interactions in sensory receptors.

The specific types of relationships that exist between sensory nerve fibers and the associated epithelial cells have been reviewed in a variety of sensory systems. In many sensory systems, perhaps most, specificity of terminal epithelial element provides a degree of specificity to the cytologic pattern of the terminal receptor. We can see examples of such interaction, not only in the case of intraepithelial nerve fibers where nerves tend to be associated with Merkel cells, but also in the case of corpuscular receptors, both of these being examples of mechanosensory systems. Equivalent types of specificity are present within the special senses, where a specific receptor cell can be described. These findings strongly suggest that specificity in the peripheral nervous system is the rule rather than the exception, a thesis proposed over a hundred years ago by F. Merkel.

Embryonic maturation of sensory terminals of primate facial hairs.

The present study examines the sequence of maturation of sensory nerve terminals that can be identified on primate facial guard hairs. At birth, the sensory innervation of both guard and vellus hairs is mature in that lanceolate, Ruffini, and free nerve ending (FNE) terminals can be identified and resemble those of the adult. Presumptive lanceolate terminals can be identified at the beginning of the third trimester of gestation, and other axons present are either Ruffini or FNEs, but definite identification is not possible. In the latter half of the second trimester only axons arranged circumferentially are present, resembling FNE or Ruffini terminals. Some of these axons directly abut the hair follicle and might eventually become lanceolate endings. The earliest nerve terminals associated with hairs cytologically resemble FNE or Ruffini terminals. At the onset of hair differentiation in the early part of the second trimester, nerves were always associated with developing epithelial hair placodes. Branching Schwann cells in the axons radiating toward the epidermis in these youngest embryos studied were best identified by electron microscopy. The early development of afferent nerve fibers in hairy skin provides an anatomical substrate for the known reflexogenic activity of primate embryos. Adequate cytologic criteria are thus available for the identification of sensory terminals in growing, differentiating, and presumably regenerating axons in primate hairy skin.

Sensory nerve endings in rhesus monkey sinus hairs.

The sensory innervation of primate sinus hairs has been studied by light and electron microscopy. For light microscopy paraffin sections as well as thick frozen sections were impregnated with silver and compared with serial semi-thin sections of tissue prepared for electron microscopy. One type of sensory terminal is present in the epidermis surrounding the hair follicle, and four specific nerve terminals have been identified within the blood sinus. An epidermal rete ridge collar encircles the hair shaft and contains approximately 200 Merkel cell-neurite complexes. Numerous other Merkel cell-neurite complexes are present in the external root sheath of the hair follicle beneath a thick glassy membrane innervated by approximately 65 nerve fibers. At this level 10-15 lanceolate or palisade terminals are situated in the connective tissue. Up to 10 simple encapsulated corpuscles can be identified above the level of lanceolate endings and Merkel cell terminals. Ruffini corpuscles are closely applied to the glassy membrane below the lanceolate and Merkel terminals at the level where nerve fibers penetrate the capsule of the sinus. All of these terminals are supplied by 80-100 large diameter myelinated fibers distributed approximately as follows: 65 innervate Merkel cell-neurite complexes, 15 to lanceolate, 10 to simple corpuscles, and 10 to Ruffini corpuscles. The innervation of the rete ridge collar is independent of that of the sinus consisting of 10-12 fibers derived from the superficial dermal network. Each of these sensory terminals can be correlated with specific functional parameters as described in numerous neurophysiologic studies. Merkel cell-neurite complexes and Ruffini corpuscles ae slowly adapting receptors; lanceolate terminals and simple corpuscles are rapidly adapting receptors.

Degeneration and regeneration of peripheral nerve in the rat trigeminal system. II. Response to nerve lesions.

The course of vibrissa sensory receptor denervation and subsequent reinnervation was studied following transection or crush of the rat infraorbital nerve. Eighteen hours after nerve lesion, the large-diameter myelinated nerves supplying the lanceolate receptors of the intermediary zone and the Merkel cells of the stratum basale contained areas of focal axoplasmic abnormalities, and some of the nerve terminals exhibited vacuolization, mitochondrial swelling, and disruption of the neurofilament pattern. The Merkel cells and lanceolate receptors of the intermediary zone were completely deafferented by 24 hours after the nerve injuries. The Ruffini complex, free nerve endings and lanceolate receptors of the inner conical body, as well as the free nerve endings and lanceolate receptors of the connective tissue below the Ringwulst, were completely normal 24 hours after crush or transection of the nerve. These receptors underwent progressive degeneration from days 2 through 6 and the vibrissa was totally denervated by day 7. Regenerating axons were first seen entering the vibrissae 2 weeks after the crush lesion and 1 month following nerve transection. Except for a slight decrease in the percentage of Merkel cells innervated, vibrissae from post-crush animals were virtually indistinguishable from normal by 3 months. In contrast, vibrissae from rats subjected to the transection lesion exhibited evidence of misdirected axons and abnormally reinnervated receptors throughout the course of regeneration. Axons entering the hairs with the main vibrissal nerve were observed contributing to the innervation of the inner conical body, an area normally supplied exclusively by the conus nerve. Many of the lanceolate receptors contained multiple unmyelinated axons, and the usually highly ordered circular innervation of the inner conical body was markedly abnormal. It is suggested that these results may help explain the faulty sensory localization and abnormal sensations reported by patients suffering a peripheral nerve injury.

A comparative light microscopic analysis of the sensory innervation of the mystacial pad. II. The common fur between the vibrissae.

The innervation to the common fur between the vibrissae was examined in the hamster, mouse, rat, gerbil, rabbit, guinea pig, and cat. Samples were taken from central locations among the more caudal vibrissae in the mystacial pad and processed with Richardson's variant of the Bielschowsky silver technique or with Winkelmann's silver technique to selectively stain peripheral axons and terminals. Additional samples were taken among the rostral vibrissae in the rat. We found major unpredictable species-related variations in the distribution of receptor types, innervation density, and the quantity of innervation in the skin between neighboring vibrissae. The common fur is composed of numerous larger guard hairs and even more numerous smaller vellus hairs. The guard hairs usually are richly innervated with fully developed piloneural complexes composed primarily of a pallisade of lanceolate endings and a circumferential array of Ruffini and free nerve endings. The vellus hairs are usually innervated by individual or shared free nerve endings. The piloneural complexes in the cat, rat, and mouse are usually complete, whereas those in the other species were usually incomplete and lacked Ruffini endings. There is considerable interspecies variation in the relative quantity of innervation between homologous neighboring vibrissae. The quantity of innervation is related to a combination of receptor completeness, innervation density, and distance between vibrissae. The quantity of intervibrissal fur innervation is by far highest in the cat, relatively high in the rabbit, relatively low in the hamster and caudal mystacial pad of the rat, and lowest in the mouse, gerbil, guinea pig, and rostral mystacial pad of the rat. The differences in the innervation between the cat and the rabbit correlate well with published physiologic data on types of receptor units. Also, barrels are most prominent in species having relatively low quantities of intervibrissal innervation and are less prominent or absent in species having high quantities of intervibrissal innervation.

Degeneration and regeneration of peripheral nerve in the rat trigeminal system. I. Identification and characterization of the multiple afferent innervation of the mystacial vibrissae.

Light and electron microscopic techniques were utilized to examine the sensory innervation of the rat mystacial vibrissa. Each vibrissa is innervated by a large nerve bundle that enters the hair below the level of the Ringwulst and a smaller bundle (conus nerve) that pierces the capsule at the top of the hair. The main nerve bundle innervates four types of sensory receptors: (1) free nerve endings (FNEs), (2) lanceolate receptors in the connective tissue below the Ringwulst, (3) Merkel cell-neurite complexes in the outer root sheath, and (4) lanceolate receptors in the intermediary zone. The smaller nerve bundle innervates the area of the sinus hair referred to as the conical body and supplies (1) a Ruffini corpuscle, (2) FNEs, and (3) lanceolate receptors in the inner conical body. The Ruffini complex of the inner conical body and the FNEs of the dense connective tissue below the Ringwulst have not been identified in previous morphological studies of the rat sinus hair. The Ruffini corpuscle, characterized by the compartmentalization of collagen bundles by Schwann cells and fibroblasts (septal cells), encircles the hair shaft in a manner analogous to the Ruffini complexes of nonsinus hairs. Identification of this receptor in the rat vibrissa provides an anatomic explanation for physiological recordings of mystacial primary afferents with slowly adapting type II properties in the rat.

Successive waves of differentiation of cutaneous afferents in rat mystacial skin.

The present study has traced the sequence of maturation of sensory receptors in the mystacial pad of postnatal rats. At birth the follicle-sinus complexes (F-SC) are well innervated by deep vibrissal nerves although the number of axons entering the sinus is less than that in the adult. The innervation of the F-SC by the conus or superficial vibrissal nerves derived from skin nerves that form the superficial dermal nerve plexus is limited to the Merkel rete ridge collar at birth, and the innervation to the inner conical body is conspicuously absent. The inner conical body innervation begins to appear 3-4 days after birth and rapidly matures over the week. By 3 weeks of age the F-SCs have a mature sensory innervation. At birth small guard hairs are present in the intervibrissal pelage and are associated with scant axons of the superficial dermal nerve plexus, but no mature sensory terminals are present. The sensory innervation of the intervening pelage begins to differentiate during the second week and mature piloneural complexes can be recognized by 3 weeks of age. Innervation to vellus hairs is still developing at 3-4 weeks of age. These maturational changes in peripheral sensory innervation correlate with gradual changes in the structure of barrels in the first somatosensory cortex (SI). Sequential waves of differentiation of sensory receptors appear to be a general feature of neural development.

Fetal development of primate chemosensory corpuscles. I. Synaptic relationships in late gestation.

Fetal macaque chemosensory corpuscles during the last part of gestation contained chemosensory, sustentacular, and undifferentiated basal cells. Sustentacular cells had apical secretory granules and no specialized contacts with axons. Chemosensory cells contained basal collections of 80-100 nm dense core granules, and specialized axonal contacts of three types--afferent synapses, efferent synapses, and subsurface cisternae. Afferent synapses were commonly present on electron opaque cells with many 80-100-nm granules, typical 40-60-nm synaptic vesicles, and a few cisternae of smooth or granular endoplasmic reticulum. Cells with subsurface cisternae and/or efferent synapses were usually electron lucent, lacked vesicles and granules, and contained numerous intracytoplasmic cisternal elements. A continuum of intermediate forms was observed. It is postulated that transition of synaptic arrays accompanies the maturation of individual chemosensory cells.

A cytologic study of Grandry corpuscle development in chicken toe skin.

The developmental sequence of Grandry corpuscles was traced in the toe skin of embryonic, young and adult chickens by light and electron microscopy. The developing Grandry cells as well as Schwann cells can first be identified at stage 38 (approximately 12 days of incubation) due to the cytoplasmic content of scattered secretory granules of approximately 100 nm in diameter. Such developing Grandry cells are always associated with nerve fibers. During late stages (stages 40-42, 14-16 days of incubation) several immature Grandry cells formed cell clusters in the dermis. Such cell clusters were always in contact with growing nerve tips of Schwann cells. Immature Grandry cells were separated from one another and dispersed in the connective tissue compartment at stages 44-45 (near hatching). By the time of hatching the developing Grandry cells began to have the morphological characteristics of adult cells. They were relatively large in cell diameter (approximately 10 micron) containing numerous secretory granules and bundles of filamentous material. These cells had finger-like cytoplasmic processes. The Grandry cells at this time had an intimate relationship with nerve fibers and satellite cells. The fact that Grandry cells were always associated with nerve fibers throughout development would support the hypothesis that Grandry cells are derived from neural elements, perhaps neural crest. Satellite cells of Grandry corpuscles are apparently derived from Schwann cells. Grandry cells and corpuscles are adult in form by two to three months of age.

The early embryogenesis of papillary (sweat duct) ridges in primate glabrous skin: the dermatotopic map of cutaneous mechanoreceptors and dermatoglyphics.

The present study documents the early innervation of the epidermis prior to the onset of differentiation of the papillary (sweat duct) ridge in glabrous digital skin of rhesus monkey embryos measuring 45, 50 and 55 mm (crown-rump) length. We observed small papillary ridges, spaced at a distance of approximately 40 microns, projecting into the dermis in the center of the distal glabrous digital pad of digits 2-5 in the 55-mm embryo. The other digital pads lacked any sign of ridge formation. A two-dimensional, approximately hexagonal grid of afferent nerves was present in the superficial dermis of all digital and palmar pads. At regular intervals of approximately 40 microns, afferent nerves ascended from the superficial dermal nerve plexus and innervated the overlying epidermis. By electron microscopy, axonal growth cones were identified contacting Merkel cells that projected several microns down into the superficial dermis in the digital pad of digit 3. Thus, the earliest wave of differentiated dorsal root ganglion neuroblasts innervates Merkel cells. Schwann cells partially encircled these growing axon tips and could be identified by the presence of rough endoplasmic reticulum and free ribosomes. The youngest embryo studied had no sign of ridge formation; however, axons ascended from the superficial dermal nerve net at 30-40-microns intervals to innervate the epidermis. We conclude that afferent nerve fibers provide a two-dimensional grid that could modulate the spacing and arrangement of the papillary or sweat duct ridges of successive digits. Such an interaction is possible between digits based on the overlapping dermatotopic maps of each rete ridge. An abnormal fingerprint could thus reflect abnormal dorsal root ganglion neuroblasts expressed through mesenchyme and epidermis.

Degeneration and regeneration of peripheral nerve in the rat trigeminal system: III. Abnormal sensory reinnervation of rat guard hairs following nerve transection and crush.

The present study was undertaken in an attempt to better understand the abnormalities of cutaneous sensibility that are present in patients following nerve injury with concomitant cutaneous denervation and subsequent reinnervation. Reinnervated intervibrissal pelage of the rat mystacial pad was studied in silver-impregnated sections 3 and 5 months after transecting and 2 and 5 months after crushing the infraorbital nerve. The sensory terminals on guard and vellus hairs were analyzed in serial paraffin sections and in thick frozen sections. In normal rat mystacial skin, approximately nine/ten of innervated guard hairs have a typical piloneural complex consisting of a palisade of highly regular lanceolate terminals surrounded by circularly arranged Ruffini terminals and free nerve endings (FNEs). The remaining one of ten innervated guard hairs has only circularly arranged presumptive FNEs and Ruffini terminals. Vellus hairs, either singly or in clusters, typically have only circularly arranged terminals that in many cases are simple FNEs. We first recognized abnormalities in innervation of hairs following nerve transection and fully expected nerve terminals to be completely normal following nerve crush. Almost all reinnervated sensory nerve terminals associated with guard hairs were markedly abnormal following nerve transection and quantitatively abnormal following nerve crush. Following nerve transection, lanceolate terminals were almost completely absent, and they were remarkably reduced in number following nerve crush. Vellus hairs when reinnervated typically lacked the complex circular presumptive Ruffini terminals. These findings may be in part the basis for the abnormal cutaneous sensory perceptions (dysasthesias and paresthesias) noted in human subjects following damage to nerves with subsequent sensory reinnervation of the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal development of primate chemosensory corpuscles. II. Synaptic relationships in early gestation.

Fungiform papillae contained well-developed chemosensory corpuscles in macaque monkey fetuses with crown-rump lengths of 5.0-9.0 cm. These fetuses corresponded to stages from the last part of the first and beginning of the second trimester of gestation. Chemosensory cells extended from the epithelial basal lamina to the taste pore anlage at the apex of the corpuscle and had typical afferent synaptic contacts with presumptive gustatory axons. Apical secretory granules, the distinctive cytologic feature of sustentacular cells, were absent. Cells with cytologic characteristics intermediate between chemosensory cells and basal extragemmal cells were considered to be differentiating chemosensory (DC) cells and appeared to arise from existing basal cells as well as undifferentiated postmitotic cells. Although extragemmal cells were extensively coupled by gap junctions which are apparent in electron micrographs of thin sections, similar junctions were absent from chemosensory and DC cells. While having minimal structural requirements for transduction and transmission of sapid stimuli (i.e., an intraoral surface and afferent synaptic contacts) chemosensory cells lacked efferent synapses and subsurface cisternae, which can be observed at later stages of gestation. Axoaxonic synapses, present between gustatory axons in the intragemmal and extragemmal epithelium and in the subgemmal connective tissue, were observed with greater frequency than at later stages of gestation. We conclude that the differentiation of chemosensory cells precedes the differentiation of sustentacular cells by several weeks. This fact lends support to the concept that chemosensory cells are a unique identifiable cells type in all chemosensory corpuscles.

A comparative light microscopic analysis of the sensory innervation of the mystacial pad. I. Innervation of vibrissal follicle-sinus complexes.

This comparative study was conducted to provide a detailed, comprehensive description of the innervation to the follicle-sinus complex (F-SC) of mystacial vibrissae and to determine if interspecies variability in the innervation of the F-SCs may be related to differences in the structure or existence of barrels in the primary somatosensory (SI) cortex. Two silver techniques (Winkelmann on 100 micron-thick-frozen sections and Sevier-Munger on 8 micron-thick paraffin sections) were applied to comparable mystacial skin samples from adult hamsters, mice, rats, gerbils, rabbits, guinea pigs and cats. The basic structure and innervation of the F-SCs is the same in all species. Six distinct populations of sensory receptors are identified at consistent locations: Merkel endings in the epidermal rete ridge collar at the mouth of the follicle; circularly disposed presumptive lanceolate, Ruffini, and free nerve endings (FNE) in the inner conical body; longitudinal lanceolate endings in a dense palisade in the mesenchymal sheath at the level of the ring sinus; Merkel endings in the external root sheath at the level of the ring sinus; scattered corpuscular and FNEs (possibly lanceolate or Ruffini endings) in the cavernous sinus; and a few FNEs in the dermal papilla. In each F-SC, the first two locations are supplied by several superficial vibrissal nerves that arise from several small nerves that also innervate the skin between the vibrissae. These superficial nerves may innervate more than one F-SC. The next three locations are supplied by a single large deep vibrissal nerve that is derived directly from a row fascicle of the infraorbital nerve. Each deep nerve innervates a single F-SC. The source of the papilla innervation was not found. The ring sinus locations are consistently the most heavily innervated in all species. The number of axons in comparable deep vibrissal nerves is similar among the rodents, higher in the cat, and lower in the rabbit. Innervation of the inner conical body varies considerably, being dense in species that vigorously whisk their vibrissae (hamster, mouse, rat, and gerbil) and sparse or absent in species that minimally or never whisk (guinea pig, rabbit, and cat). Innervation to the cavernous sinus is sparse particularly in hamsters and gerbils. The innervation to the rete ridge is uniquely absent in the rabbit.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of different methods of protecting the myocardium on lysosomal activation and acid phosphatase activity in the dog heart after one hour of cardiopulmonary bypass.

The present study was undertaken to determine the involvement of cardiac lyososomes in injury to the myocardium after cardiopulmonary bypass. Twenty conditioned mongrel dogs, weighing 15 to 18 kilograms, were fasted overnight, anesthetized with sodium pentobarbital (30 mg. per kilogram), intubated, and maintained on positive-pressure ventilation. The femoral artery and femoral vein were cannulated for pressure measurements. After median sternotomy, intravenous heparin was administered (3 mg. per kilogram) before the aorta and the superior and inferior venae cavae were cannulated for bypass. Bypass was instituted with a Travenol modular pump and a Bentley pediatric bubble oxygenator and heat exchanger. The ultrastructural effects on the myocardium and the acid phosphatase activity in the left ventricle were compared in dogs exposed to bypass for 1 hour with varying types of myocardial support: perfusion of the coronary arteries, normothermic ischemic arrest, or selective cardiac hypothermia. The morphology of control hearts and hearts fixed after 1 hour of coronary perfusion were similar. The distribution and structure of subcellular lysosomes were the same and showed identical patterns of acid phosphatase activity. Normothermic ischemic arrest was associated with a loss of glycogen stores, disrupted sarcoplasmic reticulum and T tubules, vacuolization and decrease in matrix density of mitochondria, and separation of the intercalated discs. Lysosomal activity was absent except for occasional residual bodies in the nuclear pole zone of the myocardial cells. Selective cardiac hypothermia produced results superior to those from normothermic ischemic arrest. Although these hearts showed proliferation of the lysosomal compartment, the organelles responsible for excitation-contraction coupling were spared.

Intravascular plastic catheters. How they potentiate tumor necrosis factor release and exacerbate complications associated with sepsis.

We tested the hypothesis that long-term intravascular cannulation exacerbates the harmful effects of an infectious challenge. Four groups of rats were initially studied: rats without intravascular catheters or infection (group 1), rats without catheters with a polymicrobial infection (group 2), rats with catheters but no infection (group 3), and rats with catheters and infection (group 4). Infected animals had an increased mortality and generated a significantly increased tumor necrosis factor response compared with noninfected animals. Animals with catheters and infection generated far less cardiac output than animals from the other three groups. No histologic changes differentiated the four groups. Therefore, the presence of a sterile intravascular catheter significantly increases cardiac dysfunction and mortality rates in rats with chronic bacteremia. These results suggest that intravascular plastic catheters potentiate the destructive cascade of events produced by the host in response to bacteremia.

The enigma of sensitivity in Pacinian corpuscles: a critical review and hypothesis of mechano-electric transduction.

The present report reviews the physiological and morphological specializations of Pacinian corpuscles and other mechanoreceptors that are present in the skin and connective tissues of the body as well as the cochlea. The remarkable sensitivity of Pacinian corpuscles is such that the only form of mechanical energy that could be perceived by a Pacinian corpuscle is a sound wave. In fact the human finger as demonstrated by Munger and Ide (1987) can perceive sound waves when water is the coupling agent. The structural specializations are equally remarkable with extensive membrane specializations of both the inner core and inner portion of the outer core. The halves of the inner core are each coupled with gap junctions and the inner portion of the outer core joined with numerous tight junctions. The cleft regions have specializations involving the axolemma that consist of numerous axonal spines containing bundles of filaments projecting into the cleft of the inner core. These structural specializations are thought to represent specializations for mechano-electric transduction analogous in many respects to the hair cells of the cochlea. A hypothesis for mechano-electric transduction is presented that may account in part for the extreme sensitivity of Pacinian corpuscles and other mechanoreceptors.

Multiple afferent innervation of primate facial hairs--Henry Head and Max von Frey revisited.

Large guard hairs as well as small vellus hairs are multiple innervated having lanceolate terminals of variable number. Ruffini corpuscles consisting of fine axonal ramifications are arranged circularly and located external to the lanceolate terminals. Free nerve endings (FNE's) can also be identified on some hairs distinct from Ruffini terminals. Ruffini terminals and FNE's are usually innervated by axons from the superficial dermal nerve net whereas lanceolate terminals are innervated by axons from the deeper portions of the dermal nerve net. All guard hairs have both types of terminals (lanceolate and Ruffini) confirming Hoggan and Hoggan, Retzius and Symonowicz, and most guard hairs have presumptive FNE's. Many vellus hairs have only small Ruffini endings or FNE's. The diameter of axons supplying Ruffini terminals is 1-2 micrometer and those to lanceolate terminals is 2-4 micrometers. Axons innervating lanceolate and Ruffini terminals branch rarely as correlated with small punctate receptive fields. FNE's branch widely and are correlated with large receptive fields of known nociceptors. The multiplicity of anatomically defined terminals is consistent with the known diversity of physiologically defined hair mechanoreceptive afferents as well as perceptual complexity of human hairy skin. The concept of multiple innervation of hairs confirms Head's prediction and could provide the anatomical basis of Head's basic thesis of altered sensibilities in nerve regeneration (i.e. epicritic and protopathic responses). Head's concept of two separate nervous systems, however, is an over-simplification in the light of current knowledge.