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Biomedical subjects

A Keller

Publications and source records attributed to A Keller.

At least 145 records · Page 8Linked to original sources

Input-output organization of the rat vibrissal motor cortex.

The afferent and efferent connections of the vibrissal area of the rat motor cortex (VMCx) were investigated by injecting Phaseolus vulgaris leucoagglutinin (PHA-L) or wheat germ agglutinin-horseradish peroxidase into the physiologically defined VMCx. The VMCx formed reciprocal connections with the primary and secondary somatosensory cortex, lateral and ventrolateral orbital cortex, retrosplenial cortex, and perirhinal cortex. These corticocortical afferents originated from cell bodies in layers II-III and V, and some afferents originated from cell bodies in layer VI of the primary sensory cortex. All of the VMCs efferents terminated in layers I and V or layers I-III and V. The VMCx also formed reciprocal connections with the ventrolateral, ventromedial and centrolateral nucleus, the lateral portion of the mediodorsal nucleus and the posterior complex of the thalamus. It projected bilaterally to the caudate putamen, primarily ipsilaterally to the superior colliculus, anterior pretectal nucleus, and pontine nucleus, and mainly contralaterally to the oral part of the spinotrigeminal nucleus and the reticular formation around the facial nerve nucleus. Finally, injections of PHA-L into the superior colliculus demonstrated that this structure projected contralaterally to the lateral part of the facial nerve nucleus. These data suggest that the VMCx plays a key role in sensorimotor integration, through its extensive interconnectivity with numerous brain structures, and may modulate orientation behaviors by relaying processed information to the superior colliculus.

Animals↗

Neonatal lupus erythematosus with cardiac involvement in offspring of mothers with experimental systemic lupus erythematosus.

Neonatal lupus erythematosus (NLE) syndrome is characterized by a transient dermatitis, a variety of systemic and hematological abnormalities, and isolated cases of congenital complete heart block. The latter has been reported to be due to the presence of autoantibodies specific to La (SS-B) and/or Ro (SS-A). As female mice with experimental systemic lupus erythematosus (SLE) induced by immunization with the human monoclonal anti-DNA antibody bearing the 16/6 Id produce variety of autoantibodies including anti-Ro and anti-La antibodies, we looked for NLE related symptoms in the murine model. Offspring of BALB/c mice with SLE possessed high levels of autoantibodies that declined gradually till reduced to normal levels at day 60 after delivery. Electrocardiograms recorded in groups of offspring from mothers with experimental SLE indicated that a high percentage of the offspring had defects in their conductive system including first-, second-, and third-degree heart block, significant bradycardia, and a wide QRS complex. In contrast, a normal pattern was observed in offspring of healthy mothers.

Animals↗

Tobacco, alcohol and other drug use among college students.

Smoking, binge drinking, and illicit drug use remain common among college students. The purpose of this study was to characterize college students who smoke, and to determine the relationship between smoking behavior and alcohol and illicit drug use. Cigarette smoking, alcohol use and illicit drug use practices were surveyed at ten public colleges in Virginia. A total of 3,374 undergraduate respondents from eight schools (those with response rates > 20%) were analyzed. The one-year smoking prevalence was 23.5%. Smokers were significantly more likely to be white, female, and to have lower life satisfaction and grade point averages than nonsmokers. Students classified themselves as regular or occasional smokers. Smoking was significantly associated with binge drinking in the last two weeks and with marijuana, cocaine, and LSD use in the past year. Except for binge drinking, the associations were stronger for regular than for occasional smokers. Cigarette smoking, even occasional use, identifies a subgroup of college students who are at increased risk of binge drinking and illicit drug use. This information may be useful in developing targeted drug prevention programs.

Adolescent↗

Quantitative metabolic PET imaging of a plasma cell granuloma.

We report a patient who underwent surgical resection of two lung nodules that proved to be recurrent plasma cell granuloma, also known as inflammatory pseudotumor. Prior to surgery, positron emission tomography (PET) was performed with 18F-labeled fluoro-2-deoxy-D-glucose (18FDG) and rubidium-82 (82Rb). The 18FDG PET scan revealed that the nodules corresponded to two areas of intense uptake. PET imaging with 82Rb, the marker of flow, also showed intense uptake. Thus, PET demonstrated both a high degree of metabolic activity and increased perfusion. These features suggest a lesion with high cellular activity rather than a simple reparative process. The true nature of this lesion remains unknown.

Animals↗

[Asymptomatic varicella infections in pregnancy: detection and problems].

Two cases of asymptomatic varicella infection during pregnancy will be presented. The diagnosis was made by the evidence of varicella-zoster-virus (VZV)-specific IgM or by the significant increase in antibody titer. The incidence of such subclinical VZV infections must be the issue of further investigations. Because of the rare occurrence of an embryopathy no general screening is usually made. On the other hand serological testing is recommended in cases of VZV infection in the surroundings of a pregnant woman. The problem of false-positive enzyme immunoassays make it necessary to confirm the results with one, or better two, additional methods.

Adult↗

Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A.

Severe insulin resistance type A is due to mutations in the insulin receptor gene and is characterized by glucose intolerance or diabetes mellitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recently, we showed that glucose levels in three such patients are promptly lowered by an i.v. bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare patients again and determined fasting and postprandial glucose, insulin, C-peptide, proinsulin and lipid levels during five control, five treatment and three wash-out days while on a constant diet. Treatment consisted of 2 x 150 micrograms rhIGF-I/kg sc per day, which elevated total IGF-I levels 4.5-fold above the control. Fasting glucose levels (days 1-5) in the two patients were 9.6 +/- 1.3 and 9.2 +/- 1.2 mmol/l, respectively, and fell to 4.4 +/- 0.4 and 5.1 +/- 0.5 mmol/l on treatment days 8-10. Fasting insulin (2950 +/- 450 and 690 +/- 125 pmol/l), C-peptide (2217 +/- 183 and 1317 +/- 235 pmol/l) and proinsulin control levels (125 +/- 35 and 66 +/- 0 pmol/l) also decreased by approximately 65% during rhIGH-I treatment, as did the respective postprandial levels. Lipid levels hardly changed at all. In conclusion, IGF-I appears to correct partially some metabolic sequelae of severe insulin resistance and may, hence, be used as a new therapeutic agent.

Adolescent↗

Parental representation in suicidal adolescents: a controlled study.

One hundred and eighty-seven adolescents referred to outpatient and residential services in three Canadian cities were assessed for lifetime suicidal ideation and attempt, and administered the Parental Bonding Instrument (PBI). Suicidal adolescents of both genders reported lower care and higher over-protection in relation to their mothers than non-suicidal subjects, and female subjects reported this pattern for their fathers as well. Male subjects did not show clear differentiation between groups on PBI ratings for their fathers. Mean PBI scores for female subjects indicated subjects with no suicidal ideation, those with suicidal ideation only, and those having made suicide attempts to be on a continuum, but findings for males did not. The findings extend previous reports of higher "affectionless control" in suicidal adults, but suggest that this pattern may be stronger in females than males, and that maternal influences may be stronger than paternal influences.

Adolescent↗

[Pharmacokinetics of two theophylline sustained-release preparations in healthy humans].

In an open, randomized change-over study the steady state profile of two theophylline (CAS 58-55-9) sustained-release preparations (Theophyllard resp. reference preparation) in 24 healthy volunteers was evaluated with respect to AUC, Cmax, Cmin, and tmax. Cmax of the test preparation is higher than that of the reference. During the daytime the adjusted Cmax-values are about 25% higher than the Cmax-values of the reference, during the night they are 10% higher. Tmax of the test preparation is 6 h; tmax of the reference is 5 h.

Adult↗

[Increase in polyclonal immunoglobulins: a possible useful aid in diagnosis of uveitis caused by sarcoidosis].

BACKGROUND: Polyclonal elevation of immunoglobulins is classically described in sarcoidosis and could possibly be useful in the work-up of suspected sarcoidosis uveitis. Because exposure to viruses of the herpes group is high in all populations, determination of herpes serologies is probably suited for this purpose. PATIENTS AND METHODS: Therefore serum anti-herpes antibody patterns in sarcoidosis (SARC), HLA-B27 positive acute anterior uveitis (AAU), pars planitis (PP) and healthy age-matched controls were analysed. Frozen sera were analysed for exposure to CMV, HSV, VZV by ELISA IgG testing and to EBV-VCA by immunofluorescence. Complement fixing titers > or = 1/40 and an EBV-VCA titer > or = 1/1280 were considered elevated. For each patient exposed to 2 or more herpes viruses, a score made out of the number of elevated titers divided by the number of herpes viruses the patient was exposed to, was calculated and mean scores were compared using Student's t-test. RESULTS: Mean score of patients with sarcoidosis was 0.47 +/- 0.27 (N = 18, mean age 60.2 +/- 21.4 years), significantly higher than AAU (N = 21; score 0.12 +/- 0.2; p < or = 0.000), than PP (N = 20; score 0.18 +/- 0.2; p < 0.003), and than age-matched healthy controls (N = 341, mean age 59 +/- 5.5 years; score = 0.15 +/- 0.14; p < 0.000). CONCLUSION: Anti-herpes antibodies were found to be significantly elevated in sarcoidosis uveitis, suggesting that herpes serologies may be useful in the work-up of suspected ocular sarcoidosis, a disease for which sufficiently sensitive and specific tests are lacking.

Adult↗

Synaptic relationships involving local axon collaterals of pyramidal neurons in the cat motor cortex.

The intracortical synaptic relationships of pyramidal neurons in the cat motor cortex were studied by intracellular recording and labeling techniques. Neurons that responded with monosynaptic excitatory postsynaptic potentials (EPSPs) to microstimulation in the somatosensory cortex were identified by intracellular recordings. Long-term potentiation (LTP) was evoked in all of these neurons (n = 15), following tetanic stimulation (50 Hz, 5 s) of their afferents from the somatosensory cortex. Three of these cells (cells A-C) were identified as pyramidal neurons, following intracellular injections of Neurobiotin. The intracortical axon collaterals of these labeled cells arborized extensively, forming terminal clusters both in close proximity to the parent soma and along their long, horizontal branches. Terminal clusters in both the proximal and in the distal termination zones of each of the cells were studied by electron microscopy. In their proximal arborization zones, the axon collaterals of the labeled pyramidal neurons synapsed preferentially with dendritic spines belonging to other pyramidal cells. In contrast, in their distal terminal clusters, the axon collaterals of each of the cells formed synapses in different proportions with different postsynaptic targets. The distal axon collaterals of cell A formed 86% of their synapses with pyramidal neurons; those of cell B formed 64% of their synapses with pyramidal cells, the remaining synapses with the dendritic shafts and somata of nonpyramidal neurons, and those of cell C provided most of their output (68%) to nonpyramidal, presumably inhibitory neurons. These findings suggest a high selectivity of intrinsic axon collaterals to form specific patterns of synapses. The patterns of synaptic interactions formed by these intrinsic axon collaterals may be a substrate for shaping and modulating representation maps in the motor cortex.

Animals↗

[Spondylogenic cervical myelopathy: conservative and surgical therapy].

The symptoms and signs of spondylotic cervical myelopathy (SCM) in the elderly are variable, but an ataxic-spastic gait disturbance combined with tingling in the finger tips and clumsy hands are often encountered. SCM is due to degenerative changes of discs and osseous and ligamentous structures with compression of the spinal cord. The symptoms, signs, surgical and conservative treatment, and outcome were retrospectively analyzed in 36 patients. Most of the patients undergoing surgery (n = 22) improved their clinical score and maintained this improvement for the period of observation; the non-operated patients (n = 14) had a very slow progression. Diagnostic difficulties and problems of the surgical and conservative approaches are discussed.

Adult↗

Intrinsic connections between representation zones in the cat motor cortex.

The functional organization of intrinsic connections in the cat motor cortex was examined by combining intracortical microstimulation with neuroanatomical tracers. After single injections of a dye into a cortical site from which wrist flexion was evoked, clusters of retrogradely labeled somata and of anterogradely labeled axon terminals were found throughout the forelimb representation zones. These intrinsic connections rarely involved representation zones of the hindlimb or the face musculature. These data indicate that extensive intracortical connections mediate reciprocal synaptic interactions among groups of cells involved in the execution of different movement segments. These clustered, horizontal connections may be used for coordinating the activity of different cortical representations for the execution of complex movements, and may also be involved in the pliability of motor representation maps.

Animals↗

The patterns and synaptic properties of horizontal intracortical connections in the rat motor cortex.

1. The laminar distribution of synaptic activity in the primary motor cortex, elicited by stimulation of intracortical, horizontal afferents, was studied in young (12-17 days old) and adult rats using the in vitro brain slice preparation. Connectivity patterns were deduced from current-source density (CSD) analyses of field potential depth profiles and were confirmed by anatomic data of retrograde cell labeling after focal injections of a fluorescent tracer. 2. According to the CSD distributions, horizontal axons in layer II/III provide strong monosynaptic input to dendrites of layer II and III pyramidal cells in a distant column, and weaker monosynaptic input to layer V and VI cells by synapsing on dendritic fields at the border of layer III and V and in deep layer V. When these pathways are activated, layer II/III cells may relay excitatory activity to upper and deep layer V, as well as to other cells in layer II/III of the same column. Axons arising from layer V provide monosynaptic input to pyramidal cells in all layers of neighboring columns, by synapsing in two dendritic fields: one in the superficial layers and the other in middle layer V. Activation of these pathways may generate a disynaptic intracolumnar input from layer II/III cells to middle layer V, as well as to other cells in layer II/III. Similar patterns of synaptic activity were elicited by stimulation from 0.45 to 2 mm distal to the recorded column. There were no apparent differences between young and adult rats in the connectivity patterns revealed by the CSD analyses. 3. Tracer injections in layer III resulted in retrograde labeling of cells in layers II/III and V, at distances > 2 mm from the injection site, whereas injections in layer V resulted in retrograde labeling of cells at long distances in layer V and to a lesser extent in layer II/III. These findings indicate that neurons in layer V project, via horizontal axon collaterals, for long distances within layers III and V, whereas the horizontal axon collaterals of layer III cells are restricted, for the most part, to the superficial layers. 4. Suppression of inhibitory activity by bath application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline methiodide (BMI) did not alter the pattern of the CSD distributions. All synaptic currents present in the control medium were enhanced by application of BMI, although the effect was more pronounced on the polysynaptic components.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Cholesteryl ester loading of mouse peritoneal macrophages is associated with changes in the expression or modification of specific cellular proteins, including increase in an alpha-enolase isoform.

This report explores the hypothesis that massive cholesteryl ester (CE) accumulation in macrophages, such as that occurring in atheroma foam cells, results in changes in the expression or modification of specific cellular proteins. Two-dimensional (2-D) gel electrophoretic patterns of metabolically labeled cellular proteins from mouse peritoneal macrophages that were loaded with CE (through incubation with acetylated low density lipoprotein [acetyl-LDL] for 4 days) were compared with those of control macrophages. Densitometric analysis of 2-D gel autoradiograms from the cell lysates revealed statistically significant changes in seven cellular proteins (five decreases and two increases). The changes in protein expression (foam cell versus control) ranged from a 458 +/- 164% (p < 0.001) increase to a 35 +/- 34% (p < 0.001) decrease (n = 11). Incubation of macrophages with beta-very low density lipoprotein, which also increased the CE content of macrophages (albeit to a lesser extent than acetyl-LDL), resulted in changes in five of the seven proteins. In contrast, incubation of cells with LDL, fucoidan, or latex beads, none of which caused CE accumulation, did not lead to significant changes in four of these five proteins. One of these four proteins, which increased fourfold to fivefold in foam cells (M(r) = 49,000; isoelectric point of 6.8), was purified by preparative 2-D gel electrophoresis. Internal amino acid sequence of cyanogen bromide fragments of this protein as well as Western blot analysis identified this protein as an isoform of alpha-enolase. The increased expression of this alpha-enolase isoform, which was seen as early as day 2 of acetyl-LDL incubation of the macrophages, was diminished by including an inhibitor of cholesterol esterification during the acetyl-LDL incubation period. In conclusion, macrophage foam cell formation is associated with distinct changes in protein expression, including a marked increase in an isoform of alpha-enolase, suggesting a specific biological adaptation to CE loading.

Amino Acid Sequence↗

Insulin-like growth factor I stimulates lipid oxidation, reduces protein oxidation, and enhances insulin sensitivity in humans.

To elucidate the effects of insulin-like growth factor I (IGF-I) on fuel oxidation and insulin sensitivity, eight healthy subjects were treated with saline and recombinant human (IGF-I (10 micrograms/kg.h) during 5 d in a crossover, randomized fashion, while receiving an isocaloric diet (30 kcal/kg.d) throughout the study period. On the third and fourth treatment days, respectively, an L-arginine stimulation test and an intravenous glucose tolerance test were performed. A euglycemic, hyperinsulinemic clamp combined with indirect calorimetry and a glucose tracer infusion were performed on the fifth treatment day. IGF-I treatment led to reduced fasting and stimulated (glucose and/or L-arginine) insulin and growth hormone secretion. Basal and stimulated glucagon secretion remained unchanged. Intravenous glucose tolerance was unaltered despite reduced insulin secretion. Resting energy expenditure and lipid oxidation were both elevated, while protein oxidation was reduced, and glucose turnover rates were unaltered on the fifth treatment day with IGF-I as compared to the control period. Enhanced lipolysis was reflected by elevated circulating free fatty acids. Moreover, insulin-stimulated oxidative and nonoxidative glucose disposal (i.e., insulin sensitivity) were enhanced during IGF-I treatment. Thus, IGF-I treatment leads to marked changes in lipid and protein oxidation, whereas, at the dose used, carbohydrate metabolism remains unaltered in the face of reduced insulin levels and enhanced insulin sensitivity.

Adult↗

[Myiasis in female travelers to the tropics].

Myiasis is a rare disease in Europe and the USA; it is defined by the development of parasitic, mostly tropical maggots in the human body. They are best identified by the pattern of their terminal spiracles and the shape of their stigmal plates. In spite of the size of the larvae of Cordylobia anthropophaga, there is only low-grade inflammation; the clinical course is benign.

Aged↗

Borderline disorder and attachment pathology.

In this paper, the authors investigate the theoretical and empirical association between dysfunctions of the attachment system and borderline personality disorder. Attachment theory focuses on the maintenance of a sense of safety and security through a close personal relationship with a particular person. Based on a biological behavioural system, functional attachment relationships in adulthood rely on experiences and expectations of security within the relationship. These issues are also important to the definition and dynamics of borderline personality disorder. The dimensions and patterns of reciprocal attachment were compared with other scales measuring components of psychopathology and interpersonal relationships. In a sample of 85 female outpatients, only four of the attachment scales--feared loss, secure base, compulsive care-seeking and angry withdrawal--identified patients with high scores on a measure of borderline disorder. Of these four scales, feared loss had the predominant effect. These empirical results support the hypothesized relationship between dysfunctions of the attachment system and borderline disorder.

Adult↗