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The anesthetic agent as an extra-integumentary foreign body in the respiratory tract. A new theory of general anesthesia.

Two cases are cited of patients who sometimes exhibited a condition of temporary unconsciousness which proceeded to spontaneous recovery without harmful sequelae. This type of cerebral arrest is frequently called general anesthesia:however, these patients had not received any drugs. What they did have was an irritant in the respiratory passages as shown by coughing. Three cases of general anesthesia are described wherein the duration of the phenomenon appeared to be partly due to the presence of an extra-integumentary foreign body, confined to the respiratory passages. In this trio there was evidence that the drugs did not affect the patients in any unusual way, whatever their effects on whichever side of the alveolar walls. Many anesthetic agents act like unabsorbable foreign bodies, in that they enter and leave the body unchanged, despite the fact that they do pierce the integument. Of course, almost everything, except inspirable and expirable air, but including anesthetic agents, is a foreign body in the respiratory tract. On the basis of these considerations, I suggest that one way, in which general anesthetic agents work, is an extra-integumentary foreign bodies, causing Reflex Coma by irritating or stimulating the trigger points in the walls of the respiratory tract, thereby arresting the cerebrum.

Anesthesia, General↗

[Functional and morphological changes in the gastrointestinal tract in experimental burn shock].

The gastrointestinal tract was examined in 56 dogs during burn shock (over 72 hours after injury). It was shown that burn shock entails acute catarrhal or erosive gastroenterocolitis at the basis of which there lie microcirculatory disorders and the decreased content of the "protective mucus" (glycosaminoglycans) in the integumentary epithelium. Combined therapy that normalizes primarily the circulatory channel and output of glycosaminoglycans leads to the reduction of the intensity of the above-mentioned processes in the gastrointestinal wall and prevents, to an appreciable degree, the development of erosive and ulcerous lesions.

Animals↗

Changes in the structure and function of the multicatalytic proteinase (proteasome) during programmed cell death in the intersegmental muscles of the hawkmoth, Manduca sexta.

The intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta are a well-characterized model system for examining the biochemical changes that accompany programmed cell death during development. These giant muscles die during a 30-hr period in response to a decline in the circulating titer of the insect molting hormone 20-hydroxyecdysone. When the ISMs become committed to die, there are dramatic increases in both ubiquitin expression and ubiquitin-dependent proteolysis. Since the multicatalytic proteinase (MCP) is responsible for ATP/ubiquitin-dependent proteolysis in cells, we examined its composition and properties. The purified enzyme from whole larval integumentary tissues resembles MCPs isolated from other species with respect to subunit composition and general catalytic properties. However, when MCP was isolated from condemned ISMs, we observed an approximately ninefold increase in proteinase activity compared to MCP from precommitment muscles. This increase in proteolytic activity was correlated with an approximately eightfold increase in the absolute amounts of MCP protein as determined by Western blotting and densitometry. When purified MCP from condemned muscles was examined by two-dimensional polyacrylamide gel electrophoresis, four new subunits that were not detected in the precommitment muscles were present. Correlated with the addition of these new subunits was a dramatic increase in the levels of immunodetectable MCP throughout the cytoplasm and within the nuclei of dying muscles. These changes in MCP were regulated by the same hormonal signals that mediate cell death. These data are consistent with the hypothesis that when the ISMs become committed to die, more MCP accumulates in cells and new subunits are synthesized that change both the enzymatic properties and the conformation of MCP, which in turn participates in the dramatic proteolysis that accompanies cell death.

Amino Acid Sequence↗

The role of mechanical forces on the patterning of the avian feather-bearing skin: A biomechanical analysis of the integumentary musculature in birds.

The integumentary musculature of birds consists of three distinct components. The smooth musculature comprises feather and apterial muscles, which form a continuous musculo-elastic layer within the dermis. The feather muscles, which consistently include at least erectors and depressors, interconnect contour feathers within pterylae (i.e., feather tracts) along gridlines that are oriented diagonally to the longitudinal and transverse axes of the body. The apterial muscles interconnect pterylae by attaching to the contour feathers along their peripheries. The striated musculature is composed of individual subcutaneous muscles, most of which attach to contour feathers along the caudal periphery of pterylae A new integrative functional analysis of the integumentary musculature proposes how apterial muscles stabilize the pterylae and modulate the tension of the musculo-elastic layer, and how subcutaneous muscles provide the initial stimulus for erector muscles being able to ruffle the contour feathers within pterylae. It also shows how the arrangement of the contour feathers and integumentary muscles reflects the stresses and strains that act on the avian skin. These mechanical forces are in effect not only in the adult, especially during flight, but may also be active during feather morphogenesis. The avian integument with its complex structural organization may, therefore, represent an excellent model for analyzing the nature of interactions between the environment and genetic material. The predictions of our model are testable, and our study demonstrates the relevance of integrated analyses of complex organs as mechanically coherent systems for evolutionary and developmental biology.

Animals↗

The regulation of motile activity in fish chromatophores.

Chromatophores, including melanophores, xanthophores, erythrophores, leucophores and iridophores, are responsible for the revelation of integumentary coloration in fish. Recently, blue chromatophores, also called cyanophores, were added to the list of chromatophores. Many of them are also known to possess cellular motility, by which fish are able to change their integumentary hues and patterns, thus enabling them to execute remarkable or subtle chromatic adaptation to environmental hues and patterns, and to cope with various ethological encounters. Such physiological color changes are indeed crucial for them to survive, either by protecting themselves from predators or by increasing their chances of feeding. Sometimes, they are also useful in courtship and mutual communications among individuals of the same species, leading to an increased rate of species survival. Such strategies are realized by complex mechanisms existing in the endocrine and/or nervous systems. Current studies further indicate that some paracrine factors such as endothelins (ETs) are involved in these processes. In this review, the elaborate mechanisms regulating chromatophores in these lovely aquatic animals are described.

Amino Acid Sequence↗

Botryomycosis in acquired immunodeficiency syndrome.

The first case, to our knowledge, of an integumentary form of botryomycosis is reported in a homosexual man with acquired immunodeficiency syndrome. Anal fistula and ischiorectal and gluteal abscesses developed following severe cryptosporidial diarrhea. Grains composed of gram-positive cocci were identified in the suppurative exudate. The grains had attached to multinucleated macrophages, many of which contained clusters of cocci in their cytoplasm. It is postulated that the cocci were able to survive and probably replicate in the cytoplasm of multinucleated macrophages, and were subsequently extruded as grains. These observations suggest a defect in intracellular killing of cocci by the monocyte-macrophage system. This may relate to failure in induction of control of macrophage activity by T4-inducer subsets.

Abscess↗

Distribution of griseofulvin in the rat: comparison of the oral and topical route of administration.

Effective penetration of griseofulvin across the dermal barrier has been achieved using an anhydrous solvent system of benzyl alcohol (10%), acetone (40%), and isopropanol (50%). There were quantitative differences in the relative accumulation of griseofulvin in skin compared with internal organs, when the topical and oral routes of administration were compared. The topical route enhanced localized concentrations of griseofulvin at the site of application, and these persisted for several days. After daily topical application a steady state was reached at day 3, when the diffusion across the skin barrier and epidermal loss seemed to equal the total amount applied to the skin surface. The application of griseofulvin topically, required a much smaller amount of drug to achieve similar integumentary levels compared with the amount required orally.

Administration, Oral↗

The physiology of flatfish chromatophores.

Most flatfish, of the order Pleuronectiformes, possess a white lower side, and a brown or grey upper side. This upper side can display integumentary patterning with dark areas and colored or white spots. Chromatophores in flatfish are dermal and epidermal melanophores, as well as dermal xanthophores, erythrophores, iridophores, and leucophores, combinations of which contribute to the color and patterning. Cellular studies demonstrate pattern-related differences in numerical distribution between the types of chromatophores, and in their size, both of which will enhance contrast between areas of the pattern. As well as these morphological characteristics, there are also clear physiological differences, with melanophores from various areas of the patterns demonstrating differential responsiveness to background and to stress/excitement stimuli. Regulation of flatfish melanophore responses is predominantly neural, through the sympathetic nervous system; the pituitary hormones in these fish function in maintaining final equilibria in physiological adaptations to backgrounds. Melanophores from main components of patterns also respond differently in vitro to electrical stimulation, to pituitary hormones, and to sympathomimetic drugs and their antagonists. Sensitivity characteristics with alpha- and beta-adrenergic pharmacological reagents in vitro indicate the existence of a pattern-related balance in alpha- and beta-adrenoceptor mediation in melanophore regulation. The patterning mechanism is complex, with both morphological and physiological differences at the chromatophore level, as well as involvement of central processing and control, which remains to be analysed.

Animals↗

Nail changes associated with scleroderma: a case report.

A case report and literature review on the association of nail changes and scleroderma was presented. The exact etiology of these nail changes seen in scleroderma and of the disease entity itself, has not yet been determined. The current treatment regimen, which is at best supportive, was discussed. Proper treatment of the nail changes depends on a good understanding of what to expect as the disease or condition progresses to its later stages. The extent and severity of the onychodystrophy can be correlated with the duration of the disease. Nonetheless, there are still questions that remain to be answered regarding the nail changes associated with scleroderma. For example, are these nail changes the result of Raynaud's phenomenon and its associated arterial insufficiency, or are they a normal sequelae of the integumentary degeneration so characteristic of scleroderma? Whatever the answer may be, it should be recognized that these changes are a source of clinical concern. Practitioners should take note of this clinical entity and record their findings so that these perplexing questions, as well as many others, may be discussed in the future.

Adult↗

In vivo ovine flap model to evaluate surgical infection and tissue necrosis.

Although the inciting causes and the end results of soft tissue infection are well described, we have not achieved a quantitative methodistic description of the sequence of events in between. The following study presents an isolated in vivo model which will allow specific manipulations and quantifications of the events of integumentary infection. Pedicle flaps were raised on the buttock of the adult range ewe and it was multiply inoculated with Staphylococcus aureus, and followed for 96 hr. This pedicle contains not only a well-defined artery, vein, and nerve, but also a well-developed efferent lymphatic vessel. In addition, the distal portion of the flap is primarily supplied by a musculocutaneous arterial perforator, making the distal flap a watershed area. Anatomic, radiologic, and vital stain injection studies confirmed these results. The sheep model was found to be superior to the pig model both in terms of its anatomy (the addition of an efferent lymphatic vessel) as well as the disposition of the sheep which was more compliant than that of the pig. We believe that this flap will allow multiple manipulations and provide an in vivo isolated system to study the pathobiology of soft tissue infection.

Animals↗

Chloride transport across the integumentary epithelium of Manduca sexta (Lepidoptera: Sphingidae).

Moulting fluid of Manduca sexta contains high concentrations of potassium and bicarbonate (100 mM) and low concentrations of chloride (5 mM). This fluid begins to disappear from the exuvial space approximately 9-10 h before the actual shedding of the integument. During this time, the integument can be isolated in an Ussing cell and electrical properties measured in vitro. In a normal 32 mM KHCO3 saline, potential difference (PD) is around 10 mV, exuvial side positive, and short-circuit current (SCC) is 15-20 microA cm-2. Substitution of chloride slightly reduces both PD and SCC, although resistance does not change significantly. Measurement of chloride transport in the absence of K+ indicates that 100% of the SCC can be accounted for by the net chloride flux (approximately 2 microA cm-2). The Km and Jmax for transepithelial chloride transport are 14 mM and 0.1 microEq cm-2 h-1. Bilateral potassium addition stimulates chloride transport, doubling net chloride flux as potassium concentration increases from 2 to 5 mM. Chloride net flux is not inhibited by the presence of furosemide (1 mM), nor in HCO3- -free saline by thiocyanate (1 or 10 mM) or acetazolamide (0.1 mM), but is inhibited by 100% N2. The pattern of chloride transport in M. sexta is similar to that previously reported for the rectum of locusts. As chloride is normally at low concentrations in the moulting fluid, it is suggested that this transport system acts to maintain low intracellular concentrations which may be necessary for enzymatic functions in the epidermal cells and has little importance in fluid transport.

Animals↗

Recognition of melanoma cell antigens with antibodies present in sera from patients with vitiligo.

BACKGROUND: Patients with vitiligo show specific losses of integumentary melanocytes, probably due to autoimmunity against melanocytes. We attempted to determine the presence of antibodies against pigment cell antigens in the sera of vitiligo patients. METHODS: Detergent-solubilized human melanoma cells were submitted to electrophoretic separation and immunoblotted against serum samples obtained from 19 patients with vitiligo and from 20 age- and sex-matched healthy individuals. RESULTS: Eighty-nine per cent of patients with vitiligo had antibodies to one or more pigment cell antigens. Similar antibodies were detected in 20% of healthy individuals. Antigens of 165, 90, and 68 kDa were recognized by the antibodies present in sera from 11%, 26%, and 37% of vitiligo patients, respectively, and in none of the normal sera. All patients with familial vitiligo also had antibodies to these three proteins. CONCLUSIONS: Proteins of 165, 90, and 68 kDa are specifically recognized by antibodies present in the sera of vitiligo patients and in all patients with genetic vitiligo. Whether or not these proteins might be implicated in the destruction of melanocytes by the immune system in vitiligo remains to be evaluated.

Antibodies↗

Effect of heavy metals on the uptake of [3H]-L-histidine by the polychaete Nereis succinea.

Integumentary uptake of [3H]-L-histidine by Nereis succinea was measured in the presence and absence of selected heavy metals and the amino acid L-leucine in 60% artificial seawater (ASW). The time course of 10 microM [3H]-L-histidine uptake into worms over a 60 min incubation was approximately doubled in the presence of 0.5 microM zinc and when calcium in the incubation medium was reduced from 6 mM to 5 microM the stimulatory effect of zinc on amino acid accumulation was reduced and uptake under the latter conditions was approximately half that of the control. Zinc stimulation of [3H]-L-histidine influx was a hyperbolic function of zinc concentration over the range 0 to 50 microM metal and displayed an apparent activation or affinity constant of 385+/-127 nM Zn(2+). The hyperbolic stimulatory effect of 1 microM Zn(2+) on the time course of 10 microM [3H]-L-histidine uptake was abolished in the presence of 25 microM L-leucine, suggesting that this amino acid shared the same transport system as [3H]-L-histidine and acted as a potential competitive inhibitor. Influx of [3H]-L-histidine was a hyperbolic function of external amino acid concentration and displayed an apparent affinity constant (Km) of 23.71+/-5.02 microM and an apparent aximal velocity (J(max)) of 4701+/-449 pmol/g dry wt.x15 min. Addition of 0.5 microM zinc resulted in a four-fold increase in J(max) and a doubling of K(m), suggesting the effect of the metal was mostly on the rate of amino acid transport. [3H]-L-histidine influx was mildly stimulated by Fe(2+) (0.5 microM), but was unaffected by either Ag(+) or Al(3+) (both at 0.5 microM). These results suggest that [3H]-L-histidine uptake into worm integument may take place by the classical Na(+)-independent L-transport system shared by L-leucine and regulated by exogenous calcium and other divalent metal concentrations.

Animals↗

Integumentary L-histidine transport in a euryhaline polychaete worm: regulatory roles of calcium and cadmium in the transport event.

Integumentary uptake of L-[(3)H]histidine by polychaete worms (Nereis succinea) from estuarine waters of Oahu, Hawaii was measured in the presence and absence of calcium and cadmium using a physiological saline that approximated the ion composition of 60 % sea water. In this medium 1 micromol L(-1) cadmium significantly increased (P<0.01) the uptake of 10 micromol L(-1)L-[(3)H]histidine, while 1 micromol L(-1) cadmium plus 25 micromol L(-1)L-leucine significantly decreased (P<0.01) amino acid uptake. L-[(3)H]histidine influx was a sigmoidal function (n=2. 21+/-0.16, mean +/- s.e.m.) of [L-histidine] (1?50 micromol L(-1)) in the absence of cadmium, but became a hyperbolic function with the addition of 1 micromol L(-1) cadmium. A decrease of calcium concentration from 6 to 0 mmol L(-1) (lithium substitution) significantly increased (P<0.01) amino acid influx in the presence and absence of cadmium. Calcium significantly reduced (P<0.01), and cadmium significantly increased (P<0.01), L-[(3)H]histidine influx J(max), without either divalent cation affecting amino acid influx K(t). Variation in external sodium concentration (0?250 mmol L(-1)) had no effect on 10 micromol L(-1)L-[(3)H]histidine influx, but amino acid entry was a sigmoidal function of both [cadmium] (n=2.34+/-0.44) and [lithium] (n=1.91+/-0.39) in the absence of calcium. A model is proposed for transapical L-[(3)H]histidine influx by a transporter that resembles the classical sodium-independent L-system carrier protein that is regulated by the external divalent cations calcium and cadmium.

Animals↗

Peripheral patterns of calcitonin-gene-related peptide general somatic sensory innervation: cutaneous and deep terminations.

The distribution of calcitonin-gene-related peptide (CGRP) immunoreactivity (IR) was studied in peripheral tissues of rats. The ganglionic origin, somatosensory nature, and anatomic relations of this thin-axon population were evaluated with particular emphasis on possible nociceptive roles. In animals untreated with colchicine, CGRP-IR is found in a vast proportion of small- and medium-diameter sensory ganglion cells that give rise to numerous thinly myelinated and unmyelinated axons that display CGRP-IR throughout the body. The integumentary innervation consists, in part, of an extensive subpapillary network largely traced to dermal blood vessels, sweat glands, and "free" nerve endings, some of which are found within regions containing only mast cells, fibroblasts, and collagen. Dermal papillae contain CGRP-IR axons surrounding each vascular loop; other papillary axons end freely or occasionally surround Meissner corpuscles. Intraepithelial axons enter glabrous epidermal pegs, branching and exhibiting terminals throughout the stratum spinosum. A similar pattern is found in hairy skin with additional innervation entering the base and surrounding the lower third of each hair follicle, but apparently not supplying sebaceous glands and arrector pili muscle. Axons innervating nonkeratinized oral epithelium are similar or greater in number and distribution compared to epidermis, often with more extensive branching. The high density of intraepithelial CGRP-IR innervation does not appear to correlate with the sensitive mechanoreceptor-based increase in spatial sensory discriminative capacities in the distal portions of the limb. In deep somatic tissues, CGRP-IR is principally related to vasculature and motor end plates of striated muscle, but there is an extensive network of thin axons within bone, principally in the periosteum, and focally in joint capsules, but not in relation to muscle spindles or tendon organs. These findings, together with the distribution in cranial tissues described in an accompanying paper (Silverman and Kruger: J. Comp. Neurol. 280:303-330, '89), are considered in the context of a "noceffector" concept incorporating the efferent role of these sensory axons in various tissues. It is suggested that involvement in tissue maintenance and renewal during normal function, as well as following injury, may predominate over the relatively infrequent nociceptive role of this peptidergic sensory system.

Animals↗

Comparative properties of tobacco hornworm, Manduca sexta, carbonic anhydrases.

Comparative properties of midgut, fat body and integumentary carbonic anhydrases (CAs) were measured as functions of CA-catalyzed CO2 hydration or p-nitrophenylacetate (pNPA) hydrolysis in feeding larvae and pharate pupae. Alkali metal cations fully reverse the halide anion inhibition of CA catalyzed CO2 hydration during the larval but not the pharate pupal stages in development. Concentrations of acetazolamide required to inhibit 50% of tissue-specific CA-catalyzed CO2 hydration (I50) were approximately 10(-8) M. The activity profiles between pH 6.0 and 9.0 had well-defined optima around pH 8.0 with activity declining dramatically above the optima. When CA-catalyzed pNPA hydrolysis was measured between 4 and 37 degrees C, insect enzymes failed to exhibit positive Q10 values between 25 and 37 degrees C. The affinities of the hornworm CAs toward pNPA were determined with stage- and tissue-specific Km ranging from 0.42 to 8.0 X 10(-3) M. It is concluded that tissue and stage-specific CAs exist in M. sexta, whose properties appear to differ markedly with those previously reported for mammalian enzymes.

4-Nitrophenylphosphatase↗

Composite tissue allografts in rats: IV. Graft-versus-host disease in recipients of vascularized bone marrow transplants.

This laboratory has used a composite tissue allograft model as a vehicle for studies on a new type of bone marrow transplant, the vascularized bone marrow transplant. The model consists of a rat hind limb transplant that incorporates integumentary musculoskeletal, and lymphopoietic tissues. These transplants, in comparison with conventional marrow transplants, have the advantage of providing a syngeneic microenvironment and immediate engraftment of both mature and progenitor hemopoietic cells at the time of transplantation. The characteristics of graft-versus-host disease were studied in this model. Lewis X Brown Norway F1 (LBN RT-1(1+n)) rats received hind limbs from Lewis (LEW RT-1(1)) donors (n = 19). Animals were observed daily for signs of graft-versus-host disease. Necropsies were performed. A minority of animals developed lethal disease (7 of 19 recipients) and demonstrated cachexia with concomitant histopathologic changes of the disease. Acute and chronic groups emerged with distinct clinical courses, which are similar to other models of this disease. Recipients of vascularized bone marrow transplants (limb transplants) showed clinical and histopathologic changes of the disease. The transplants may be used as a model of graft-versus-host disease in humans. Most interestingly, the transplant has a lower incidence of disease compared with other methods of bone marrow transplantation and represents an alternative to conventional bone marrow transplantation, which deserves further exploration. It may be possible to develop a new technique for bone marrow transplantation based on this surgical approach. It is proposed that the transfer of vascularized blocks of bone/marrow into prospective recipients as opposed to cellular bone marrow transplants may be preferable.

Animals↗