Evaluation of the rat micronucleus test with bone marrow and peripheral blood: summary of the 9th collaborative study by CSGMT/JEMS. MMS. Collaborative Study Group for the Micronucleus Test. Environmental Mutagen Society of Japan. Mammalian Mutagenicity Study Group

The mouse has traditionally been used for the micronucleus test, with bone marrow the usual target organ. The aim of the 9th collaborative study by CSGMT was to evaluate the suitability of the rat for the micronucleus test, with bone marrow and peripheral blood as the target organ. Since the rat spleen eliminates circulating micronucleated erythrocytes, a rat peripheral blood micronucleus assay might not be feasible. Thirty-four Japanese laboratories and six overseas laboratories participated in this collaboration, and 40 chemicals were studied. As a rule, rat bone marrow and peripheral blood were analyzed using acridine orange staining. Among 36 mouse micronucleus-positive rat carcinogens, 34 of which had been evaluated by CSGMT, we observed 33 positive and three negative results with rat bone marrow and 30 positive, three equivocal, and three negative responses with rat peripheral blood. Of the two mouse micronucleus-negative rat carcinogens, acrylonitrile was positive in rat bone marrow and 4,4'-methylene bis(2-chloroaniline) was negative in both rat bone marrow and peripheral blood. Two chemicals reported to be mouse micronucleus-negative and rat-positive, azobenzene and Solvent Yellow 14, and one chemical reported to be mouse-positive and rat-negative, 1,2-dimethylhydrazine, gave positive responses in rat bone marrow and peripheral blood. The concordance between bone marrow and peripheral blood with rats was 92%. The concordance between rat and mouse erythrocytes was 88%. We concluded that the rat micronucleus assay, using either bone marrow or peripheral blood, can be used as an alternative to the mouse micronucleus assay.     

The interleukin-5 messenger RNA expression in a patient with idiopathic hypereosinophilic syndrome

Interleukin-5 has a specific role in various eosinophilic activities. It is the predominant cytokine produces by activated T-lymphocytes isolated from patients with idiopathic hypereosinophilic syndrome. We studied a young patient suffering from idiopathic hypereosinophilic syndrome who presented with Horner's syndrome, peripheral neuropathy and skin ulcers. The IL-5 gene expression by CD4+ T-lymphocytes and the peripheral eosinophil count were raised. The skin ulcers continued to deteriorate despite a swift reduction of the IL-5 gene expression and peripheral eosinophil count following systemic corticosteroid treatment. We suggest that peripheral eosinophilia may not be responsible for the damage in skin lesions and more aggressive treatment may be required.     

Facilitation of the main generator source of earthworm muscle contraction by a peripheral neuron

A constant facilitation of responses evoked in the earthworm muscle contraction generator neurons by responses evoked in the neurons of its peripheral nervous system was demonstrated. It is based on the proposal that these two responses are bifurcations of an afferent response evoked by the same peripheral mechanical stimulus but converging again on this central neuron. A single-peaked generator response without facilitation was demonstrated by sectioning the afferent route of the peripheral facilitatory modulatory response, or conditioning response (CR). The multipeaked response could be restored by restimulating the sectioned modulatory neuron with an intracellular substitutive conditioning stimulus (SCS). These multipeaked responses were proposed to be the result of reverberating the original single peaked unconditioned response (UR) through a parallel (P) neuronal circuit which receives the facilitation of the peripheral modulatory neuron. This peripheral modulatory neuron was named "Peri-K?stchen" (PK) neuron because it has about 20 peripheral processes distributed on the surface of a K?stchen of longitudinal muscle cells on the body wall of this preparation as revealed by the Lucifer Yellow-CH-filling method.     

Peripheral retinal hemorrhages: a literature review and report on thirty-three patients

BACKGROUND: Peripheral retinal hemorrhages are often asymptomatic and are detected during routine dilation. The incidence of peripheral retinal hemorrhages is unknown and there is a paucity of information on the subject available in the literature. METHODS: This article reports on 33 patients with peripheral retinal hemorrhage detected during routine fundus examination. The possible etiologies and pathophysiology of peripheral retinal hemorrhages are discussed and a management plan for the primary care clinician is presented. The ophthalmic literature was reviewed and reports of peripheral retinal hemorrhages were included. For each etiology, the ocular and systemic sequelae, symptoms, testing, treatment, and followup are delineated. RESULTS: Various proposed etiologies of peripheral retinal hemorrhages include senescence, systemic and retinal vascular disease, hematologic disorders, infectious disease, hypoxia, and mechanical and iatrogenic causes. CONCLUSION: Despite their asymptomatic nature, peripheral retinal hemorrhages have a variety of potential etiologies and risk factors. Causes associated with serious ocular or systemic complications must be identified so that appropriate treatment and followup can be instituted.     

Role of the brain in interleukin-6 modulation

High levels of interleukin 6 (IL-6) have been found in the brain tissue or cerebrospinal fluid (CSF) in several CNS disorders including Alzheimer's disease, AIDS dementia complex, multiple sclerois, stroke, Parkinson's disease, traumatic brain injuries, brain tumors and CNS infections. In these diseases, IL-6 is also found in blood showing that CNS conditions can elicit a peripheral immune response. A direct secretion of IL-6 from brain to blood has been shown to be a major mechanism by which the brain activates peripheral metabolic, endocrine and immune responses. However, this communication is not straightforward and other regulatory mechanisms are likely to be there. Several lines of evidence obtained in the laboratory have shown that the brain significantly modulates IL-6 production in the periphery. Evidence will be given that: (i) central inflammatory stimuli efficiently induce peripheral IL-6; (ii) central opioids are effective modulators of peripheral IL-6, and (iii) the sympathetic nervous system represents an inhibitory pathway to peripheral IL-6.     

The Internet: facilitating an international nursing culture for psychiatric nurses

Patients with multiple sclerosis (MS) may develop a peripheral neuropathy, sometimes attributed to nutritional deficiency. Other patients present with a demyelinating neuropathy which is presumed to be the result of an autoimmune process that affects both the central and peripheral nervous systems. We report a case of concurring MS and demyelinating neuropathy, without a positive family history, in whom genetic testing proved the neuropathy to be hereditary and not autoimmune. Hereditary neuropathy should be a consideration in sporadic cases of peripheral neuropathy and MS.     

Repair of the defect in spondylolysis. Durable fixation with pedicle screws and laminar hooks

Apoptosis is important for maintaining peripheral lymphocyte homeostasis and for minimizing the accumulation of autoreactive lymphocytes. Disruption of apoptotic pathways has been linked to lymphadenopathy, breakdown of peripheral tolerance and the development of autoimmune diseases. Major progress has been made during the past year in understanding the critical roles of a variety of signaling molecules, especially a group of cysteine proteases, for the execution of apoptosis. These proteases appear to be the primary effector molecules responsible for carrying out lymphocyte apoptosis and may be critical for peripheral immunological tolerance.     

Ovarian steroids and stress produce changes in peripheral benzodiazepine receptor density

Although past research has described changes in the density of the peripheral benzodiazepine receptor in brain and in peripheral organs in response to stressors and steroid hormone exposure, their combined influence had yet to be determined. This study examined the effect of swim-stress as a function of ovarian hormone administration on the binding of an isoquinoline carboxamide derivative, [3H]PK 11195, in brain and peripheral tissues. In olfactory bulb and adrenal gland, stress increased peripheral benzodiazepine receptor density in ovariectomized rats with and without estradiol and progesterone replacement injection, even when compared with unstressed animals treated with hormones, where estradiol + progesterone decreased peripheral benzodiazepine receptor number in olfactory bulb, but estradiol and estradiol + progesterone increased it in adrenal gland. In frontal cortex, stress decreased peripheral benzodiazepine receptor number, an effect that was reversed by estradiol. In hippocampus estradiol decreased peripheral benzodiazepine receptor density in unstressed animals and estradiol + progesterone decreased peripheral benzodiazepine receptor number in unstressed and stressed animals. In cerebellum, stress, estradiol and estradiol + progesterone alone decreased peripheral benzodiazepine receptor density. In uterus of unstressed controls, estradiol + progesterone increased peripheral benzodiazepine receptor density, and stress produced a further increase in steroid-treated females. Stress did not affect peripheral benzodiazepine receptor density in kidney, except in animals that received estradiol + progesterone injections, where swim-stress produced a significant decrease in peripheral benzodiazepine receptor density. Thus, steroid hormones regulate peripheral benzodiazepine receptor density in endocrine organs and brain, and the hormonal state of the organism modifies the peripheral benzodiazepine receptor response to stress in a tissue- and brain region-specific manner, suggesting that the peripheral benzodiazepine receptor may play a pivotal role in an integrated response to stress.     

Effect of GF120918, a potent P-glycoprotein inhibitor, on morphine pharmacokinetics and pharmacodynamics in the rat

PURPOSE: Studies have shown that 11% to 18% of patients with an abdominal aortic aneurysm (AAA) have a first-degree relative with an AAA. A familial pattern among patients with peripheral arterial aneurysms and arteriomegaly has not been reported. The objective of this study was to examine familial patterns among patients with peripheral arterial aneurysm and arteriomegaly and compare them with patterns among patients with AAA. METHODS: Pedigrees were constructed for first-degree relatives of patients who received the diagnosis of peripheral arterial aneurysm, arteriomegaly, or AAA from 1988 through 1996. The presence of aneurysms and risk factors was confirmed for patients and relatives by means of telephone interviews and review of hospital and physician records. RESULTS: Seven hundred three first-degree relatives older than 50 years were contacted for 140 probands with peripheral arterial aneurysm, AAA, or arteriomegaly. There were differences in risk factors for hernia and diabetes mellitus among the probands with peripheral arterial aneurysm, AAA, or arteriomegaly but none for relatives. Patients with peripheral arterial aneurysm (n = 40) had a 10% (4/40) familial incidence rate of an aneurysm, patients with AAA (n = 86) had a 22% (19/86) familial incidence rate, and patients with arteriomegaly (n = 14) had a 36% (5/14) familial incidence rate. AAA (24/28, or 86%) was the aneurysm diagnosed most commonly among first-degree relatives. Most aneurysms (85%) occurred among men. CONCLUSION: There appears to be a gradation of familial patterns from peripheral arterial aneurysm to AAA to arteriomegaly among patients with degenerative aneurysmal disease, and there appears to be a predominance among men. Relatives of patients with any of the 3 lesions-peripheral arterial aneurysm, AAA, arteriomegaly--most frequently have AAA. Relatives of patients with AAA, peripheral arterial aneurysm, or arteriomegaly may be screened by means of a physical examination for peripheral aneurysmal disease. Screening by means of ultrasound examination of the aorta should be limited to first-degree relatives of patients with aortic aneurysms or arteriomegaly.     

Initial experiences with the MR "magnitude contrast angiography of the lower extremities

45 patients with occlusive peripheral vascular disease were examined by MR angiography in a retrospective study. A FISP 3D sequence was used by acquiring a rephased and a dephased data set. The individual slices were post-processed by using a maximum-intensity-projection algorithm. The MRA results of the popliteal and tibioperoneal arteries were compared to conventional or digital angiography. In comparing these techniques MR angiography cannot be accepted for pre- and postoperative staging of patients with occlusive peripheral vascular disease. In future new MRA techniques may be useful in postoperative staging of patients with peripheral vascular stenosis.     

Membranous glomerulonephritis associated with inflammatory demyelinating peripheral neuropathies

A 55-year-old man with chronic inflammatory demyelinating polyradiculoneuropathy developed the nephrotic syndrome. Renal biopsy showed stage I membranous glomerulonephritis. Review of the literature revealed the association of these two rare syndromes, considered to be due to immunologic dysfunction, in two other cases, as well as several cases of the acute form of demyelinating peripheral polyradiculoneuropathy. The nephrotic syndrome appears to be persistent in the chronic form of the peripheral neuropathy but reversible in its acute form following immunosuppressive therapy. The possibility of a common immunopathogenesis in the association of membranous glomerulonephritis and inflammatory demyelinating peripheral neuropathies deserves further scrutiny.     

Coronary heart disease and peripheral arterial occlusive disease, with particular reference to myocardial infarction (author's transl)

Coronary heart disease and peripheral arterial vascular disease are parts of a systemic disease. Starting from manifest myocardial infarction, the simultaneous existence of peripheral arterial occlusive diseases in Fontaine's Stages I and II was detected in 176 out of a total of 193 patients with myocardial infarction. The frequency of concomitant coronary and peripheral vascular obstruction was 65.9-94.1% in the three studies carried out. In coronary heart disease without infarction the frequency of a coincident attack in both vascular areas was 87.9%. In 27.8 to 33.3% of the patients with myocardial infarction, signs of peripheral occlusive disease could be demonstrated already before the onset of infarction. The mutual relationships between coronary and peripheral arterial occlusive diseases are of particular significance for the rehabilitation measures striven for.     

Distribution of antigen specific memory T cells in lymph nodes after immunization at peripheral or mucosal sites

The distribution of antigen-specific memory T cells in different lymph nodes of sheep was determined using an antigen-specific in vitro proliferation assay. Lymph nodes were collected from sheep immunized simultaneously with avidin or ovalbumin in a peripheral tissue site (hind leg muscle) and keyhole limpet haemocyanin (KLH) in an intestinal tissue site (gut wall or colonic mucosa). The results showed a consistently high proliferative response in typical peripheral lymph nodes (popliteal and prescapular) and a low or negative response in gastrointestinal lymph nodes (abomasal and jejunal) while the response in other nodes was variable. The low proliferative response in the gastrointestinal lymph nodes was not due to the presence of suppressor CD8- lymphocytes and the proliferative response could not be raised to peripheral lymph nodes levels with the addition to cultures of IL-2 or mitomycin-C treated peripheral lymph node cells. The high proliferative response in the peripheral lymph nodes was not suppressed by the addition of mitomycin-C-treated gastric lymph node cells but was dramatically reduced by the addition of mAb against the IL-2-receptor or by depletion of CD4- T cells. The results suggest that antigen-specific proliferative memory T cells, which may be Th1-like memory cells, preferentially migrate to peripheral lymph nodes independent of their site of induction.     

Histological identification of Lugaro cells in the cat cerebellum

Segmental loss of a peripheral nerve has been a challenging reconstructive problem. Management of the nerve gap has been accomplished classically with nerve grafting. However, autogenous nerve grafts are not always available for bridging large nerve gaps, and clinical results of large nerve cable grafts have been disappointing. Newer techniques concentrate on nerve lengthening with different methods. Tissue expansion of peripheral nerves has been producing promising results. Since the introduction of the Ilizarov external fixator, much attention has turned to limb-lengthening techniques and studies investigating the results of nerve and soft tissues lengthened during the course of this procedure. Primary nerve distraction may be an alternative to nerve elongation, by expansion or nerve grafting to repair the peripheral nerve gap. This study describes a device and a model for peripheral nerve distraction in a rat. Primary nerve distraction will need to be subjected to vigorous studies before clinical application.     

Moving vernier in amblyopic and peripheral vision: greater tolerance to motion blur

The purpose of this study was to examine the hypothesis that higher stimulus velocities could be tolerated in amblyopic and normal peripheral vision. The basis for this hypothesis is that a shift in the spatial scale of processing appears to account for the degradation in vernier acuity for moving stimuli in normal vision, and, to a large degree for the degradation in vernier acuity for stationary stimuli in amblyopic and peripheral vision. Vernier thresholds were determined using a pair of long abutting lines, for velocities ranging between 0 and 8 deg/sec. Comparisons were made between non-amblyopic and amblyopic eyes in two amblyopic observers, and between central and peripheral (5 and 10 deg) vision in two normal observers. We analyzed our threshold vs velocity data using an equivalent noise analysis, and defined the knee of the function, the point at which vernier threshold is elevated by a factor of square root of 2, as the "critical velocity" beyond which image motion degrades vernier acuity. Critical velocities were found to be higher in amblyopic than in nonamblyopic eyes; and higher in peripheral than central vision. Our results are consistent with the predictions from the shift in spatial scale notion--that higher velocity of image motion can be tolerated because of the shift in sensitivity toward lower spatial-frequency filter mechanisms in amblyopic and normal peripheral vision.     

Balloon rupture during peripheral stent implantation: a new technique for balloon retrieval

Balloon rupture is a known technical problem with implantation of vascular stents. In most cases, the ruptured balloon can be retrieved with simple maneuvers. In this case report, a peripheral balloon became trapped within an undeployed peripheral vascular stent and could not be removed by application of standard maneuvers. A novel approach to balloon retrieval was devised and undertaken with success.     

Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo

Following exposure to some types of antigen (superantigens), responsive T cells expand and then decline in numbers, a phenomenon that has been called 'peripheral deletion'. This process may play a role in limiting autoimmune reactions and in the maintenance of immune homeostasis. Here we describe experiments on peripheral deletion in mice carrying the lpr/lpr defect, which has been shown to be due to defective production of the CD95/Fas molecule. Young lpr/lpr mice with no apparent immunologic abnormalities display a defect in bacterial superantigen-induced peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion in normal animals is dramatically reduced in the mutant mice. Further, the levels of Fas on responding cells in normal mice increases and decreases together with increases and decreases in cell numbers, suggesting that cells with the highest levels of Fas are preferentially deleted. These observations are consistent with the known ability of CD95 to transduce a signal leading to apoptosis, and they implicate this signal transduction pathway in peripheral deletion. In contrast, bacterial superantigen-induced deletion of thymocytes appears to be fully functional in these mice, and thus Fas/APO-1 does not appear to be required for this process. Further, antibody ligation of the TCR on activated T cells from normal or young lpr/lpr mice can induce apoptosis and therefore under some circumstances this phenomenon is not dependent upon CD95/Fas. Thus, to avoid autoreactivity and ensure immune homeostasis, several different apoptotic mechanisms exist in peripheral T lymphocytes, only some of which involve Fas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between homeobox-containing gene MSX1 and the occurrence of limb deficiency

Impaired exercise capacity is a common finding in chronic obstructive pulmonary disease (COPD) patients. This reduction is not a simple consequence of airflow limitation. Peripheral muscle weakness, deconditioning and impaired gas exchange, were recognized as important contributors to exercise intolerance. In this overview, the contribution of peripheral muscle function and muscle training to exercise performance is discussed by means of three questions: 1) Is peripheral muscle dysfunction contributing to exercise limitation in COPD? 2) How do we measure peripheral muscle function? 3) Are peripheral muscle training modalities effective? At present, there is substantial evidence for peripheral muscle dysfunction. Both reduced force generating capacity as well as impaired muscle metabolism were observed and these findings contributed substantially to the reduced exercise capacity in COPD. Peripheral muscle strength measurements are feasible with mechanical or electronic devices and revealed muscle weakness in COPD patients. However, this weakness is not uniform for all muscle groups. Upper arm and leg muscles were more affected than hand muscles. This may, at least in part, be related to differences in the levels of inactivity between leg and hand muscles. In addition, muscle weakness is associated with impaired exercise capacity and symptoms of increased exertion during exercise. Endurance exercise training, i.e. cycling and treadmill walking, improved exercise capacity and was associated with alterations in muscle metabolism. Strength training of peripheral muscles showed increases in submaximal exercise performance and quality of life measures. These improvements were observed independently of the degree of airflow obstruction. The optimal training regimen (strength or endurance), and the muscle groups to be trained, remain to be determined.