Sensory processing in the deep spinal dorsal horn of neurokinin-1 receptor knockout mice.

Background: The neurokinin-1 receptor and its primary ligand, substance P, are widely recognized as contributing to the spinal processing of nociceptive stimuli, yet the specific function of the neurokinin-1 receptor remains unclear.

Methods: To better clarify these functions, the authors examined the neurophysiologic responses of L4-L5 neurons in the deep dorsal horn to acute mechanical, thermal, and electrical stimuli in knockout and wild-type mice. In addition, the capacity of knockout and wild-type mice to show wind-up to repeated C-fiber stimuli and to show sensitization after cutaneous mustard oil was assessed.

A novel gene expressed in human keratinocytes with long-term in vitro growth potential is required for cell growth.

The herpes simplex virus large subunit of ribonucleotide reductase differs from its counterparts in eukaryotic and prokaryotic cells and in other viruses in that it contains a unique domain that codes for a distinct serine-threonine protein kinase that activates the Ras/MEK/MAPK mitogenic pathway and is required for virus growth. Previous studies suggested that ribonucleotide reductase protein kinase was co-opted from a cellular gene. Cellular genes similar to ribonucleotide reductase protein kinase were not cloned, however, and their function is unknown.

Nerve injury-induced mechanical but not thermal hyperalgesia is attenuated in neurokinin-1 receptor knockout mice.

Mice lacking the gene encoding for substance P and neurokinin A, or the NK-1 receptor, exhibit alterations in behavior to various acute nociceptive stimuli. However, behavioral responses of NK-1 mutant animals have not been well characterized in models of chronic pain. We studied the behavioral responses of NK-1 knockout and wild-type control mice to thermal and mechanical stimuli before and after inducing chronic neuropathic pain by unilateral ligation of the L5 spinal nerve.

Neurokinin-1 receptors are involved in behavioral responses to high-intensity heat stimuli and capsaicin-induced hyperalgesia in mice.

Background: The neurokinin-1 (NK-1) receptor and its ligand, substance P, are thought to play important roles in nociception and hyperalgesia. This study evaluated the role of the NK-1 receptor in processing noxious stimuli in normal and inflammatory states.

Methods: Behavioral responses to heat and mechanical and chemical stimuli were studied in NK-1 receptor knockout mice and wild-type control mice.

Characterization of an aFGF gene expression vector with therapeutic potential.

Background: Topical application of growth factors to wounds has proven to be suboptimal in achieving epithelial growth and accelerating healing. We propose transfection of fibroblasts with a gene for acidic fibroblast growth factor (aFGF) which will allow continuous, local delivery of the growth factor to wounds, ulcerative lesions, or healing tissues.

Methods: We utilized a pMEXneo vector containing the human aFGF gene with a secretory signal sequence from the hst/KS3 gene to obtain continuous secretion of therapeutic doses of aFGF.

Neuropeptide regulation of proinflammatory cytokine responses.

Severe traumatic injuries and infections are frequently accompanied by life-threatening shock and are associated with increases in the proinflammatory cytokines, particularly tumor necrosis factor alpha (TNF-alpha). The body's first perception of injury is the nociceptive or pain response. This response is induced at the site of injury and is transmitted systemically by sensory neuropeptides, the tachykinins, released from sensory afferent c-fiber neurons.

HIV infection and aging: mechanisms to explain the accelerated rate of progression in the older patient.

Age is an important predictor of progression in HIV infections. Not only do older individuals' develop AIDS more rapidly than younger persons, they die more quickly after developing an AIDS-defining illness. While the elderly have higher morbidity and mortality rates from viral and bacterial infections, the mechanism(s) responsible for the more rapid progression of HIV infection in older individuals has not been described.

Effect of hemocarboperfusion on organ blood flow and survival in porcine endotoxic shock.

Objective: To evaluate the effects of hemocarboperfusion on hemodynamics, organ blood flow, and survival in endotoxin shock.

Design: Prospective, placebo-controlled, animal trial.

Setting: Research laboratory in a major university teaching hospital.

Interactions of ACTH and TGF beta on monocyte proliferation: implications for trauma and burn patients.

The purpose of this study was to try to elucidate a possible biobehavioral mechanism associated with decreased immune function in trauma patients by determining whether there is an interaction between the effects of ACTH, a stress hormone, and TGF beta, a cytokine, on peripheral blood lymphocyte proliferation. Peripheral mononuclear lymphocytes (PMLs) from healthy donors were preincubated with varying concentrations of ACTH for 24 hr, stimulated with concanavalin A and increasing concentrations of TGF beta, and incubated for 72 hr. Proliferation was assayed by tritiated thymidine incorporation.

Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-alpha release.

Urethan is a commonly used animal anesthetic for nonrecovery laboratory surgery. However, urethan has diverse biological effects that may complicate the interpretation of experimental findings. This study examined the effect of urethan on the response to an intravenous bolus of lipopolysaccharide (LPS; 30 mg/kg) in rats.

Inhibition of apoptosis in polymorphonuclear neutrophils from burn patients.

Normal human polymorphonuclear neutrophils (PMN) undergo rapid apoptosis during in vitro culture. In contrast, apoptosis is inhibited in PMN from patients with severe burns. This inhibition is not an inherent property of the cells but is caused by thermolabile factors present in the plasma.

Regulation of acute phase gene expression following surgery and endotoxin administration in the anesthetized pig.

Background: The hepatic acute phase response (APR) reflects an organism's integrated response to stress. This APR results in augmented synthesis and secretion of specific procoagulants and antiproteases and a complementary decrease in the synthesis and secretion of several constitutive proteins, such as albumin. The cytokines tumor necrosis factor (TNF) or interleukin-6 (IL-6) have been identified as proximal mediators of the APR in response to endotoxin stress.

Translocation. Incidental phenomenon or true pathology?

Objective: This study was conducted to determine if reduction of early postburn endotoxemia influences the cytokine cascade, clinical manifestations of sepsis, and mortality rate.

Summary Background Data: Translocational endotoxemia has been demonstrated postburn in animals and humans. Endotoxin is known to induce the cytokine cascade, which leads to the clinical manifestations of sepsis.

Effect of anesthesia and surgery on plasma cytokine levels.

Cytokines released in response to stress may have a profound impact on circulatory stability. There is no information on the effect of general anesthesia alone on plasma cytokine levels and little information on cytokine release following surgery. Plasma cytokine levels and hemodynamic parameters were measured during anesthesia and abdominal surgery under sterile and nonpyrogenic conditions in seven pigs anesthetized with ketamine and pentobarbital.

Increased production of TGF-beta and Il-6 by aged spleen cells.

Aging is accompanied by a progressive decline in immunity in every species that has been studied. Despite its ubiquity, the causes of immunosenescence are unknown. Transforming growth factor beta (TGF-beta) is a cytokine with potent immunosuppressive properties.

Inhibitory effects of interleukin 6 on immunity. Possible implications in burn patients.

Certain disease states are associated with abnormal increases in the monokine interleukin 6. Increased levels of interleukin 6 have been demonstrated in serum from patients with burns and are associated with systemic increases in endotoxin levels. Using a murine in vitro experimental model, we have studied the effects of interleukin 6 on various measures of immunity.

The Baltimore Sepsis Scale: measurement of sepsis in patients with burns using a new scoring system.

A new sepsis scale has been developed, and it consists of 13 parameters, each of which is measured daily on a variable point scale. In 41 patients with major burns the Baltimore Sepsis scale correlated well with death or survival, with occurrence of septicemia, and with the level of serum interleukin-6. It did not correlate well with the level of plasma endotoxin or with the type of organism that was grown in blood cultures (gram-positive or gram-negative).

Altered organ growth and zinc and copper distribution in endotoxin-treated neonatal mice.

Organ weights and the distribution of zinc and copper were compared in HLA/ICR mice that received intraperitoneal injections of 10 micrograms of Serratia marcescens lipopolysaccharide W or of sterile physiologic saline at 2 d of age. Between 5 and 28 d of age, body weight gains were similar in both groups. At 5 and 7 d of age, lipopolysaccharide W-treated mice had significantly lower thymus weights (p less than 0.

Pathologic concentrations of interleukin 6 inhibit T cell responses via induction of activation of TGF-beta.

Interleukin 6 levels are increased in a variety of clinical conditions including bacterial and viral infections, HIV infection, autoimmune diseases, certain neoplasias, and traumatic injury. In general, all these conditions are characterized by suppression of one or more manifestations of the immune response. Concentrations of IL 6 comparable to those found in the sera of immunosuppressed, thermally injured patients selectively inhibit T cell proliferative responses.

Increased levels of circulating interleukin 6 in burn patients.

The serum levels of interleukin 6 (IL-6) were determined in a population of burn patients. In all patients, IL-6 levels were increased over a 3-week interval with peak concentrations reached during the first week after injury. Patients receiving intravenous polymyxin B therapy according to a regimen designed to reduce endotoxemia manifested greatly reduced levels of both circulating endotoxins and IL-6.

Control of endotoxemia in burn patients by use of polymyxin B.

A group of patients with severe burns were entered into two sequential prospective randomized trials for reduction of endotoxemia by the use of intravenous polymyxin B. The first group underwent polymyxin administration during the first week after burn injury in a bell-shaped dosage form constructed to resemble the level of endotoxemia as previously documented. This group showed a statistically highly significant reduction in endotoxin levels and a suggestive, but not statistically significant, reduction in wound infection and mortality in the treated group compared with controls.

Influence of age upon the metabolism of zinc in livers of C57BL/6J mice.

The kinetics of accumulation and loss of zinc from the liver following subcutaneous administration of 10 mg of zinc per kg were examined in young adult (6 months old) and old (24 months old) male C57BL/6J mice. After zinc treatment, total liver zinc concentrations rose equally in both groups and returned to basal levels at 96 h post treatment. However, differences were found in the subcellular distribution of zinc in these two age groups.

Altered expression of lymphocyte Il-2 receptors in burned patients.

Impairment of T-cell function is a consistent observation in burned patients. Concomitant with this impairment is an increase in serum factors which inhibit interleukin-2-mediated T-cell functions. These factors are heat labile and do not behave like endotoxins.

Supplemental zinc restores antibody formation in cultures of aged spleen cells. III. Impairment of II-2-mediated responses.

The effects of zinc on interleukin-2(IL-2)-dependent T cell responses of lymphocytes from immunodepressed aged mice and from young adult animals were studied. Concentrations of zinc which have been shown to restore antibody formation in cells from aged mice and to increase the production of Il-1 and Il-4 inhibited the production of Il-2. Cells from both young adults and aged mice were inhibited similarly.

Activation of thymocyte responses to interleukin-1 by zinc.

In vitro proliferative responses of murine thymocytes to interleukin-1 are enhanced by supplementing the cultures with the trace nutrient zinc. Zine not only enhances the responses of cells suboptimally activated by PHA but can also prime the cells to respond to IL-1 in the absence of activation by PHA. Zinc affects the early stages of the proliferative response.