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Biomedical subjects

E Sprecher

Publications and source records attributed to E Sprecher.

At least 73 records · Page 4Linked to original sources

Corpus cavernosum electromyogram: spontaneous and evoked electrical activities.

Sympathetic skin responses recorded from the surfaces of limbs and the penis resemble the waveforms recorded by needle from the corpora cavernosa. Thus, corpus cavernosum electromyography might reflect a systemic sympathetic response rather than unique smooth muscle corporeal activity. We recorded electrical activity simultaneously from the corpora and limbs of 10 subjects. Spontaneous activity was unique to the corpora, while electrical activity in response to sympathetic activating maneuvers was found simultaneously in the corpora and limbs (Fisher's exact test, p < 0.001). It is concluded that 2 types of electrical activity can be recorded from the corpora--spontaneous activity, which might reflect specific smooth muscle activity, and response activity, which is part of the systemic response to sympathetic stimulation.

Adult↗

Variance of sensory threshold measurements: discrimination of feigners from trustworthy performers.

Sensory threshold measurements are criticized as subjective and therefore not to be relied upon in clinical diagnostic practice, particularly when deliberate deception by the patient is suspected. In an attempt to devise a method which permits dependable sensory threshold interpretation, individual variability of thresholds was examined in normal and neuropathic subjects. Normals were also instructed to feign sensory impairment resulting from hypothetical injury. For each subject, a number of threshold readings were averaged, yielding individual means and variances. Feigning normal subjects evidenced a larger variance compared to trustworthy normal and neuropathic subjects. Thus, alertness to variance reinforces the psychophysical analysis: small variance values suggest trustworthy normal or pathological results, whereas large variance calls the interpreter's attention to feigned results or inattentive test performance.

Cold Temperature↗

Thermal testing: normative data and repeatability for various test algorithms.

Measurement of thresholds for warm and cold sensation was performed on 106 normal subjects, at thenar eminence and foot dorsum. Three test algorithms were used, the reaction-time-inclusive method of limits, and reaction-time-exclusive methods of levels and staircase. Tests were repeated 2 weeks following the first for most of the subjects, and after elimination of 5 outlying subject data points, and determination of no systematic relationship between magnitude and variability of test scores, data from between 72 and 76 subjects were used to derive repeatability coefficients, by ANOVA-based procedures which extend standard repeatability assessment methods. Normative data tables are presented, with measures of repeatability for the various algorithms and modalities. Method of limits tests exhibited inter-session bias, and large repeatability coefficients, compared with methods of levels and staircase, which exhibited no bias and had better (lower) repeatability coefficients. All three methods had similar test durations. We conclude that on the basis of these data, the reaction-time-exclusive methods of levels and staircase have a definite advantage over the method of limits.

Adult↗

Role of Langerhans cells and other dendritic cells in viral diseases.

Langerhans cells are part of a vast system of potent antigen-presenting cells known under the name of dendritic cells. During the last decade, much has been learned on dendritic cell involvement in the immune response to infectious diseases. This review briefly summarizes our current understanding of the role played by Langerhans cells and other dendritic cells in the pathogenesis of DNA and RNA virus infections. These data may form the basis for the development of innovative approaches in the diagnosis, prevention, and treatment of viral diseases.

Animals↗

Detection of IL-1 beta, TNF-alpha, and IL-6 gene transcription by the polymerase chain reaction in keratinocytes, Langerhans cells and peritoneal exudate cells during infection with herpes simplex virus-1.

Interleukin-1, tumour necrosis factor-alpha and interleukin-6 are considered to be major mediators of inflammatory processes. In the present study, cytokine gene transcription was detected by the polymerase chain reaction technique during cutaneous and intraperitoneal infection with herpes simplex virus-1. Epidermal cell suspensions obtained from mice infected with herpes simplex virus-1 in the ear pinna were enriched or depleted in Langerhans cells by immunomagnetic fractionation. Herpes simplex virus-1 infection in the skin was found to induce interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene transcription in keratinocytes at 24 hours post-infection. Gene transcription declined by 48 hours post-infection. Induction of interleukin-1 beta and tumour necrosis factor-alpha but not of IL-6 gene transcription was detected in Langerhans cells obtained from infected mice at 24 hours post-infection. In order to study cytokine gene transcription during intraperitoneal infection with herpes simplex virus-1, peritoneal exudate cells were obtained from infected mice. Maximal levels of interleukin-1 beta, tumour necrosis factor-alpha, and interleukin-6 mRNA were found in peritoneal exudate cells 6 hours after infection. RNA transcription declined at 24 hours post-infection and was no longer detectable at 48 hours post-infection. Since the higher susceptibility of newborn mice to intraperitoneal herpes simplex virus-1 infection has been suggested to be related to defective cytokine production, cytokine gene transcription was compared in peritoneal exudate cells obtained from infected newborn and adult mice. No significant differences in interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene expression were observed in peritoneal exudate cells obtained from newborn mice as compared with adult mice. In conclusion, cutaneous and intraperitoneal infection with herpes simplex virus-1 induces interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene transcription in epidermal and peritoneal exudate cells.

Animals↗

Interleukin-1 alpha gene-transcription in murine keratinocytes is inhibited by HSV-1 infection.

The effect of in vitro infection with herpes simplex virus 1 (HSV-1) on the Interleukin-1 (IL-1) activity of murine keratinocytes was investigated. IL-1 alpha mRNA synthesis was measured by the Northern blot technique, and the IL-1 protein production was measured in terms of the ability of dialysed supernatants from cultures of uninfected and HSV-1 infected keratinocytes to enhance mitogen-induced murine thymocyte proliferation. IL-1 alpha mRNA-synthesis in uninfected keratinocytes was detected 24 h and 48 h after isolation of the keratinocytes. IL-1 protein secretion by these keratinocytes was measureable at 18 h and reached a peak of 73 h, whereas intracellular and membrane-bound IL-1 protein production reached a maximum after 25 h. Keratinocytes, which had been cultured in vitro for 18 h, were infected with HSV-1 for 2 h and further cultured for an additional 4 h or 22 h before IL-1 measurements. A marked reduction of IL-1 alpha gene-expression was noted 6 hours after HSV-1-infection of keratinocytes, and nearly total shut-off was detected after infection for 24 h. Reduced gene-expression was paralleled by a reduction in the IL-1 protein secretion from the HSV-1 infected keratinocytes.

Animals↗

Effect of genetically determined immunodeficiency on epidermal dendritic cell populations in C57BL/6J mice.

Mice homozygous for three different recessive mutations known to cause pleiotropic defects in the immune system and in the skin were used to evaluate the relationship between the classical immune system and dendritic epidermal cell populations. Numbers of Langerhans cells (LCs) and Thy-1+ dendritic cells (Thy-1+DEC) were determined using indirect immunofluorescence microscopy of epidermal whole mounts taken from viable motheaten (mev), nude (nu), and rhino (rhhr) mice. All mutants were maintained on the C57BL/6J strain background and were compared with their respective littermate normal controls. Viable motheaten mice had normal numbers of LCs at 1 month of age. However, by 8 weeks of age, LC density had decreased threefold. Nude and rhino mice had normal numbers of LCs at all ages tested. There was no significant effect of the viable motheaten mutation on numbers of Thy-1+DEC. Although nude mice showed normal numbers of Thy-1+ DEC at 1 month of age, these athymic mice had a threefold decrease in numbers of such cells by 6 months. In contrast to the reduced numbers of Thy-1+DEC seen in nude mice, rhino mice showed a four- to fivefold increase in the numbers of these epidermal cells at all ages tested. These findings suggest new mouse models for investigating the development, regulation, and biological properties of epidermal dendritic cell populations.

Animals↗

Induction of interleukin-1 alpha and beta gene transcription in mouse peritoneal exudate cells after intraperitoneal infection with herpes simplex virus-1.

Macrophages have been shown to play a determining role in the immune defense against herpes simplex virus-1 (HIV-1) intraperitoneal infection in the mouse. In the present study, the effect of HSV-1 infection on interleukin-1 alpha and beta gene transcription in peritoneal exudate cells was investigated. HSV-1 infection was found to induce interleukin-1 alpha and beta gene transcription in these cells. Induction of the interleukin-1 beta gene initiated 6 h postinfection (p.i.) and terminated at 48 h p.i. In contrast, interleukin-1 alpha RNA was detectable at high levels at 6h p.i. but not at 24 h p.i. Inactivation of virus prior to infection prevented HSV-1-induced IL-1 gene induction, indicating that only infectious virus is able to stimulate IL-1 gene transcription. These findings are discussed in relation to the role of macrophages in the immunological mechanisms of defense against HSV-1 infection.

Animals↗

Mouse footpad Langerhans cells as an indicator for safety of foot and mouth disease virus vaccines.

The effect of various vaccines against foot and mouth disease virus (FMDV) was tested on Langerhans cell density in the footpad epidermis of mice. Injection of monovalent, bivalent and trivalent FMDV vaccines caused a reduction in Langerhans cell density in the murine skin, which was more marked at the center of the footpad, the site of injection, than at the periphery. Testing of the various components of the vaccine showed that saponin caused a marked reduction in Langerhans cells while injection of aluminium hydroxide had a lesser effect and the virus alone had no effect on these cells. Thus Langerhans cell density could serve as an efficient marker to test the safety of vaccines to FMDV since the integrity of Langerhans cells, which are the antigen-presenting cells in the skin epidermis, is needed for an effective immune response to the vaccine.

Adenosine Triphosphatases↗

Effect of aging on epidermal dendritic cell populations in C57BL/6J mice.

The density and function of epidermal dendritic cell populations were investigated in aged C57BL/6J mice. The densities of both Langerhans cells (LC) and Thy-1+ dendritic epidermal cells were found to decrease with age. Epidermal cell suspensions from aged mice showed impaired immunologic function as assessed in vitro by the skin-lymphocyte reaction assay and by measuring the ability of epidermal cell suspensions to stimulate the proliferation of sensitized T cells in the presence of the sensitizing antigen. However, the capacity of LC to transport antigen from the skin to the draining lymph nodes was found in vivo to be comparable to that of young mice. Results of transplantation of bone marrow cells from young and old donors into irradiated recipients indicate that the decreased Langerhans cell density found in old mice may result from a deficiency in Langerhans cell bone marrow progenitors.

Aging↗

Langerhans cell density and activity in mouse skin and lymph nodes affect herpes simplex type 1 (HSV-1) pathogenicity.

Langerhans cells are epidermal antigen-presenting cells that function by taking up antigens in the skin, migrating to the lymph nodes, where they are designated interdigitating cells, and triggering the immune response. The role of interdigitating cells (IDC) was investigated in a murine model of herpes simplex virus-1 infection in the skin. The number of IDC in the lymph nodes began to increase on the first day following infection and reached a peak three days p.i. Low titers of infectious virus were recovered from the fraction of lymph node cells that consisted of 60-80% IDC at one day p.i. Lymph node cells that were obtained from mice immunized with HSV-1 proliferated in vitro in response to viral antigens but did not respond to mock antigens. When mice were immunized with HSV-1 inoculated into skin that had been depleted of Langerhans cells, this in vitro proliferative response was abolished. Thus, the present results suggest that Langerhans cells function in the immune defense of the skin against HSV-1 infection by transporting the virus to the peripheral lymph nodes where an immune response is initiated. Injection of the immunomodulator OK-432 into the footpad skin caused a local increase in the number of Langerhans cells in the epidermis and led to an increased migration of dendritic cells to the lymph nodes. Under these conditions, a decrease in HSV-1 pathogenicity was noted. These observations indicate that the pathogenicity of herpes simplex virus type 1 in the skin is affected by Langerhans cell density and activity in the epidermis and the lymph nodes.

Adenosine Triphosphatases↗

Langerhans cells in vaccinia virus infection in mouse skin.

Langerhans cells function as potent antigen-presenting cells in the epidermis. They were shown to play an essential role in the mechanisms of defense of the skin against viral infections. In the present study, the response of Langerhans cells to infection of the skin with vaccinia virus was investigated. Decrease in Langerhans cell density in the skin was accompanied by an increase in the pathogenicity of the WR and Noguchi but not of the Lister strain of vaccinia virus. Langerhans cell density was shown to increase rapidly at the site of inoculation with the two pathogenic strains of vaccinia virus.

Animals↗

Cytofluorometric analysis of thymic interdigitating cells from C57BL/6 mice prior and after leukemogenic X-irradiation.

The thymus is populated by various Ia+ cell populations, including epithelial cells, macrophages and dendritic cells. Thymic cell suspensions were stained with an anti-Ia antibody and shown by cytofluorometry to contain a small number of strongly Ia+ cells characterized by a large diameter. The cell population was separated with the aid of the fluorescence-activated cell sorter (FACS) and characterized. They were shown to express high levels of membranal Ia antigens; they demonstrated ATPase activity and displayed the ultrastructural features characteristic of the previously described thymic interdigitating cells. C57BL/6 mice were submitted to various regimens of X-irradiation. Whereas exposure to a single dose of X-irradiation was followed by an increase in the percentage of strongly Ia+ cells, exposure to a leukemogenic regimen of fractionated X-irradiation led to a decrease in the percentage and absolute numbers of these cells in the thymus. Of the C57BL/6 mice that were irradiated with fractionated X-irradiation, 77% developed leukemia. Intravenous injection of syngeneic bone marrow one day following the last irradiation or protection of the femur during irradiation prevented both the appearance of leukemia and the disappearance of interdigitating cells. Therefore an inverse correlation between the presence of thymic dendritic cells and the incidence of leukemia in C57BL/6 mice could be demonstrated. These findings are discussed in relation to the putative role of dendritic cells in the thymus.

Animals↗

Role of epidermal Langerhans cells in viral infections.

Langerhans cells function as highly potent antigen-presenting cells in the epidermis. In the last few years, their role in viral infections has been studied in various experimental systems. They have been shown to be involved in the pathogenesis of a number of infections of viral origin. These include vaccinia virus, human papilloma virus, herpes simplex virus, foot and mouth disease virus and human retrovirus infections. Studies on the effect of various factors, that are known to modulate the activity and density of Langerhans cell in the epidermis, may lead in the future to the development of new strategies aimed at inhibiting virus infections or even eradicating latent infection.

Animals↗

Role of Langerhans cells and Thy. 1+ effector cells in herpes simplex virus-1 infection in the skin of newborn mice.

Langerhans cells function in the epidermis as very potent accessory cells. Their role as antigen-presenting cells in the immune response following herpes simplex virus type 1 (HSV-1) skin infection of newborn mice was studied. Newborn C 57 BL/6 mice were found to be susceptible while adult mice are resistant to HSV-1 infection in the skin. Because the immune response to HSV-1 infection in the skin is mainly cell-mediated, and therefore dependent on the presence of functional accessory cells, the state of Langerhans cells in the skin of newborns was studied. Staining of whole epidermal mounts revealed similar numbers of Ia+ and ATPase+ Langerhans cells in the epidermis of newborn and adult mice. In a skin lymphocyte reaction assay, Langerhans cells derived from newborn mice were shown to stimulate proliferation of T cells derived from adult allogeneic mice to the same degree as adult-derived Langerhans cells. HSV-1 was injected into the skin of C 57 BL/6 newborn mice together with various preparations of adult-derived spleen cells devoid of antigen-presenting cells. The injected adult-derived lymphocytes were found to confer protection against HSV-1 infection in newborn mice, despite the lack of detectable antigen-presenting cell (APC) function in this cell preparation. The cell subset involved in the transfer of resistance was found to be Ia- and Thy. 1+.

Animals↗

Herpes simplex virus type 1 pathogenicity in footpad and ear skin of mice depends on Langerhans cell density, mouse genetics, and virus strain.

Skin Langerhans cells have been shown to be very efficient in presenting antigens to T-helper cells and stimulating the immune response. The present study demonstrates their essential role in the control of primary herpetic infections in the skin. Two unrelated stimuli (abrasion and steroids) were shown to cause depletion of the Langerhans cells in the murine epidermis, and both caused enhancement of the virulence of herpes simplex type 1 (HSV-1) in the skin. The Langerhans cell density was found to be lower in the skin of the ear than in the footpad. HSV-1 was consistently more virulent when injected into the ear epidermis than in the footpad. Thus, HSV-1 pathogenicity in mouse skin depends on the mouse age and strain, the virus strain, and the state of the epidermal Langerhans cells. These findings are discussed in relation to the antigen-presenting cell function of the Langerhans cells.

Age Factors↗