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At least 1,153 records · Page 64Linked to original sources
PubMed1991

Regeneration of axons from adult human retina in vitro.

In an effort to establish an in vitro model of regenerating adult human central nervous system (CNS) neurons, we have investigated the potential for neurite growth from explants prepared from normal adult human retina. Eyes (donated for corneal transplantation) were removed within 2.0 h postmortem and stored on ice for 1.5 to 7.0 days. Retinal explants (1 mm2) were prepared and cultured at 37 degrees C on cellular or acellular substrata in an oxygen-rich, humidified atmosphere. Neurite outgrowth, visualized by neurofilament immunofluorescence, was observed only in the presence of Schwann cells, after a quiescent period of approximately 6 days in vitro. Of 50 explants cultured for 7 days or more on substantia containing Schwann cells, 43 showed evidence of viability in vitro and 28 extended neurites onto Schwann cell surfaces. Estimated rates of neurite growth on Schwann cell substrata reached a maximum of 0.22 mm/day. Neurites did not grow beyond the explant border onto culture substrata composed of either polylysine, laminin, type-I collagen, or monolayers of adult human retinal glia. These results demonstrate that under selected conditions, explants prepared from adult human retina harbor viable neurons and that Schwann cells promote and support regeneration of neurites from these neurons in vitro, allowing systematic analysis of conditions favorable to axonal regeneration from adult human CNS neurons.

Axons↗
PubMed1985

1H NMR detection of cerebral myo-inositol.

A previously unassigned group of prominent multiplets of the 360 MHz 1H NMR spectrum of acid stable metabolite extracts from rat brain is shown to arise from free myo-inositol. This conclusion is derived from a systematic analysis of the high-resolution 1H NMR spectra of brain acid extracts, in which appropriate conditions and optimal proton signals have been selected for the quantitative analysis of up to 15 metabolites. Developmental variations in the cerebral content of myo-inositol could be readily detected using this approach, which provides a novel alternative to study myo-inositol metabolism under physiological or pathological conditions.

Animals↗
PubMed1996

Human testis specifically expresses a homologue of the rodent T lymphocytes RT6 mRNA.

A human homologue of the rodent T cell mono ADP-ribosyl transferase RT6 mRNA was identified by a systematic analysis of human testis transcripts. This messenger encodes for a precursor protein of 367 aa (MW: 41.5 kDa) which exhibits a peptide signal, consensus domains for mono ADP-ribosyl transferase and a C-terminal part characteristic of glycophosphatidyl inositol anchored protein. This mRNA, transcribed from a gene localized in 4q13-q21, is not expressed in white blood cells but is specific for human testis in which it is likely to correspond to a new ADP-ribosyl transferase.

ADP Ribose Transferases↗
PubMed1985

Acute changes in plasma steroids and agonistic behavior in male Japanese quail.

A systematic analysis of the acute (minutes to hours) fluctuations of plasma steroids [androstenedione (A), 5 alpha-dihydrotestosterone (DHT), testosterone (T), corticosterone (B)] was investigated in relation to the fighting behavior displayed by experienced male Japanese quail (Coturnix coturnix) in short-term (2 min) dyadic encounters. Plasma levels of hormones measured in competitors either 1 hr before, during, or 3 min to 6 hr following a fight related poorly to either the attacking or nonattacking behavior displayed by opponents. However, transient fluctuations measured by the percentage change from prefight levels of plasma DHT, T, and B were identified in individuals following the onset of the fight. Winners demonstrated significantly greater percentage changes than did the losers at 3, 32, and 362 min for DHT and T and at 7 min for B. These differences in hormonal responses to the fight are attributed to the more aggressive behavior displayed by the victorious opponents (winners) over their defeated competitors (losers). Significance of these rapid changes is discussed in relation to the physiology and behavior of aggressive interactions.

Aggression↗
PubMed1987

Proton magnetic resonance study of lysine-binding to the kringle 4 domain of human plasminogen. The structure of the binding site.

The binding of L-Lys, D-Lys and epsilon-aminocaproic acid (epsilon ACA) to the kringle 4 domain of human plasminogen has been investigated via one and two-dimensional 1H-nuclear magnetic resonance spectroscopy at 300 and 600 MHz. Ligand-kringle association constants (Ka) were determined assuming single site binding. At 295 K, pH 7.2, D-Lys binds to kringle 4 much more weakly (Ka = 1.2 mM-1) than does L-Lys (Ka = 24.4 mM-1). L-Lys binding to kringle 4 causes the appearance of ring current-shifted high-field resonances within the -1 approximately less than delta approximately less than 0 parts per million range. The ligand origin of these signals has been confirmed by examining the spectra of kringle 4 titrated with deuterated L-Lys. A systematic analysis of ligand-induced shifts on the aromatic resonances of kringle 4 has been carried out on the basis of 300 MHz two-dimensional chemical shift correlated (COSY) and double quantum correlated spectroscopies. Significant differences in the effect of L-Lys and D-Lys binding to kringle 4 have been observed in the aromatic COSY spectrum. In particular, the His31 H4 and Trp72 H2 singlets and the Phe64 multiplets appear to be the most sensitive to the particular enantiomers, indicating that these residues are in proximity to the ligand C alpha center. In contrast, the rest of the indole spectrum of Trp72 and the aromatic resonances of Trp62 and Tyr74, which are affected by ligand presence, are insensitive to the optical nature of the ligand isomer. These results, together with two-dimensional proton Overhauser studies and ligand-kringle saturation transfer experiments reported previously, enabled us to generate a model of the kringle 4 ligand-binding site from the crystallographic co-ordinates of the prothrombin kringle 1. The latter, although lacking recognizable lysine-binding capability, is otherwise structurally homologous to the plasminogen kringles.

Binding Sites↗
PubMed1989

Comparison of the effects of the acute administration of dexoxadrol, levoxadrol, MK-801 and phencyclidine on body temperature in the rat.

Some of the dioxolanes produce pharmacological effects that have much in common with phencyclidine and phencyclidine-like drugs. Dioxadrol can be resolved into two enantiomers, dexoxadrol and levoxadrol. Dexoxadrol has an affinity for phencyclidine receptors that is much greater than that of levoxadrol, but dexoxadrol and levoxadrol have nearly equal affinities for sigma receptors. The systematic analysis of the relative potencies of dexoxadrol and levoxadrol can be used as an approach to define effects mediated by phencyclidine vs sigma receptors. Compounds that act on phencyclidine receptors, as well as affecting behavior, alter body temperature in the rat. The purpose of the present study was to compare and contrast the effects of the acute administration of dexoxadrol, levoxadrol, MK-801 and phencyclidine on body temperature in the rat. Dexoxadrol and levoxadrol (5.0, 10.0, 20.0 or 40.0 mg/kg), MK-801 (0.12, 0.6 or 1.2 mg/kg) or phencyclidine (5.0, 10.0 or 20.0 mg/kg) were administered subcutaneously and body temperature was measured. Both dexoxadrol and MK-801 produced hyperthermia but levoxadrol did not affect body temperature. In contrast to the hyperthermic effects of dexoxadrol and MK-801, phencyclidine produced hypothermia. These findings indicate that hypothermia induced by phencyclidine is not due to interactions with phencyclidine receptors and, while dexoxadrol, MK-801 and phencyclidine may share some similar receptor binding and behavioral characteristics, they can be differentiated on the basis of their effects on body temperature.

Animals↗
PubMed1994

Ultrastructural changes in the adult rat thymus after estradiol benzoate treatment.

Although numerous authors have correlated high levels of circulating estrogens with thymic involution, a systematic analysis to date on the histological changes affecting the thymus gland in that situation is lacking. In the present study we report both histological and ultrastructural changes occurring in the thymus of adult Wistar rats which received a single dose either of 100 micrograms or 500 micrograms of estradiol benzoate. Both doses induced thymic involution which correlated well with histological changes observed in the lymphoid populations but also with profound modifications in the thymic epithelial component. Moreover, intrathymic erythro-and granulopoiesis, increased numbers of both macrophages and plasma cells, and important variations in the thymic vascular permeability occurred in estradiol benzoate treated rats. These results are discussed from the perspective that changes in both the non-lymphoid cell components of thymic microenvironments and vascular permeability are essential to understand the general effects of sex steroids on the immune system.

Animals↗
PubMed1985

Standardization of CDI-mediated DTPA-coupling to IgG and IgG2a antibodies for 113mIn labeling.

A systematic analysis of various factors involved in the CDI-mediated coupling of DTPA to IgG have been carried out, in order to optimize the labeling yield of a monoclonal antibody labeled to high specific activity. Various CDI-to-DTPA ratios were tested, followed by a range of DTPA (activated) to IgG ratios. Specific activities as high as 600 Ci/mmol could be obtained following labeling with 113mIn, when an IgG : DTPA : CDI ratio of 0.01 : 1:20 was used. Other aspects, such as the volume of each of the reactants, the pH and the reaction times, were also standardized to yield a labeled IgG2a (KS1/4) that could be consistently tested for biodistribution and tumor-binding.

Carbodiimides↗
PubMed1992

Nuclear installations and childhood cancer in the UK: mortality and incidence for 0-9-year-old children, 1971-1980.

Data on cancer incidence and mortality in the vicinity of nuclear installations in England and Wales have been published, covering the period 1959-1980. Several age classes and a number of cancer sites have been included. Systematic analysis has so far been limited to cancer mortality. This suggests that childhood leukemia is unusually frequent near some types of installations and the excess is greater for years 0-9 than for later ages. In the earlier decade, 1959-1969, there was questionable consistency of incidence reporting. This report uses the incidence and mortality data only for the period 1971-1980; leukemia and non-leukemia cancer data for those 0-9 years are analyzed, and consistency of incidence reporting is evaluated by comparing incidence and mortality. For comparison with reported data for grouped local authority areas (LAAs) near to 21 different installations, two sources of expected incidence are used. The first is based on regional data, and the second is based on a group of LAAs similar in location, urban/rural character and population size. Effectiveness of treatment of acute lymphocytic leukemia (ALL, the principal type among 0-9-year-old children) has improved in recent decades and this has decreased the case fatality rate, and increased the relevance of incidence data. No significant differences in the mortality/incidence ratio were found when comparing areas near installations with their matched reference areas. Although some standardized incidence ratios (SIRs) are low in comparison areas, these are a reflection of the small numbers in the denominator. Low and high SIRs are observed in both installation and comparison areas. Excluding the populations near Sellafield and Dounreay, the installations of which include nuclear reprocessing and which are reported elsewhere, children living near one of a group of six installations have significantly increased leukemia incidence. One hundred sixty-five cases were observed for the combined population group, whereas 133.6 were expected on the basis of regional data and 141.9 on the basis of comparison areas. The operations of these installations include nuclear research, nuclear fuel production, nuclear weapons manufacture, and radio-isotopic reagent manufacture and marketing. No evidence of any increase of leukemia incidence is found for populations surrounding nuclear power installations, nor in coastal communities possibly affected by Sellafield discharges.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗
PubMed1987

Recombination at the human alpha-globin gene cluster: sequence features and topological constraints.

We have characterized 170 kb of DNA around the human alpha-globin gene cluster to enable a systematic analysis of 12 naturally occurring deletions from this region. In 8 deletions, the 3' breakpoints lie within a 6-8 kb segment of DNA, identifying a breakpoint cluster region. Members of the Alu family of repetitive sequences are frequently found at the breakpoints and we describe a novel deletion due to homologous recombination between such repeats. In another deletion the breakpoints are separated by 131 bp of DNA, which we have shown to be transposed from a region 36 kb upstream from the 5' breakpoint where it is present in the inverse orientation. The sizes of these deletions, the nonrandom distribution of their breakpoints, and the nature of the inversion-duplication transposition event suggest that these rearrangements are constrained by the higher-order structure of the alpha-globin cluster.

Base Sequence↗
PubMed1979

A review of the consequences of fluid and electrolyte shifts in weightlessness.

This review describes the renal-endocrine mechanisms related to the early losses of fluid-electrolytes from the body during weightlessness as well as their contribution to longer term adaptation of fluid-electrolyte balance. The hypotheses presented were generated by a systematic analysis of body fluid and renal dynamics observed under conditions of actual and simulated spaceflight. These have increased our understanding of the effects of acute headward fluid shifts on renal excretion, the factors promoting excess sodium excretion and the regulation of extracellular fluid composition.

Adaptation, Physiological↗
PubMed1990

Health promotion for adolescents: preventive and corrective strategies against problem behavior.

This paper, in its first part, gives an overview of research on "problem behavior" in adolescence. Adolescence is considered to be a stage in life characterized by more experimentation, exploration, risk-taking, and rebellion than any other stages. Many health-damaging behaviors (drug consumption, precocious sexual activity, riskful driving, aggressive behavior, etc.) have important psychosocial functions in adolescents' developments. Some of these behaviors can be signals of "stress", defined as a bio-psycho-social state of tension resulting from a variety of stressors which confront adolescents daily in modern industrial societies. In the second part of the paper, the implications of this research for strategies of intervention are discussed. The systematic analysis distinguishes between different stages in the process by which problem behavior emerges and separates "preventive" from "corrective" forms of intervention. Additionally, the analysis differentiates between the dimensions targeted by the measures: interventions addressed toward individual behavior ("personal resources") on the one hand, and living conditions ("social resources") on the other hand. The resulting types of intervention approaches are illustrated with examples and discussed in view of how appropriate they are for health promotion in adolescence. Implications for "social policy for adolescents" are discussed.

Adolescent↗
PubMed1983

Identification of three homology classes of small, cryptic plasmids in intestinal Bacteroides species.

A systematic analysis of the plasmid content of intestinal Bacteroides spp. was made. Eight of fifteen clinical isolates and seven of nineteen normal rectal flora isolates examined contained small plasmids (less than 5 Mda). The majority of these small plasmids could be assigned to three homology classes by Southern hybridization. Further investigation demonstrated the presence of subclasses within one of the homologous classes. Class I plasmids were 1.8 Mda, Class III were 3.7 Mda, and Class II plasmids were of three different molecular weights: 2.6 Mda (IIA), 3.2 Mda (IIB), and 4.0 Mda (IIC). Among representative plasmids from each class there was remarkable sequence similarity based upon digestion patterns obtained using the restriction endonucleases, AluI and DdeI. In addition, similar polypeptide products were observed using purified Class I plasmids as template in an Escherichia coli in vitro coupled transcription-translation system. Small plasmids were found in seven of the ten recognized species of intestinal bacteroides, indicating that no species barrier exists for these plasmids. In addition, since plasmids from all three classes were found together in a single isolate, it was concluded that these plasmids are not incompatible.

Bacteroides↗
PubMed1994

Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles.

Identification of CTL epitopes for tumor-specific responses is important for the development of immunotherapies to treat cancer patients. We have developed a strategy to identify potential CTL epitopes based on screening of sequences of target proteins for presence of specific motifs recognized by the most common HLA-A alleles, and identification of high affinity binding peptides using in vitro quantitative assays. A systematic analysis using the sequence of the product of the tumor-associated MAGE-1 gene has been carried out. All possible peptides of nine and ten residues, containing binding motifs for HLA-A1, -A2.1, A-3.2, -A11 and -A24 were synthesized and tested for binding using a quantitative assay. Out of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding affinity (Kd < or = 500 nM). Several peptides were identified as good MHC binders for each one of the five HLA-A alleles studied (five for HLA-A1, 11 for HLA-A2.1, 10 for HLA-A3.2, 16 for HLA-A11 and five for HLA-A24. Furthermore, eight of these peptides were found to bind well to more than one HLA-A allele. These results have important implications for the development of immunotherapeutic vaccines to treat malignant melanoma.

Amino Acid Sequence↗
PubMed1994

A mechanism for P-glycoprotein action in multidrug resistance: are we there yet?

Multidrug resistance is associated with the overexpression of P-glycoprotein, a membrane glycoprotein. The mechanism by which P-glycoprotein confers to cells the capacity to resist cytotoxic attack by structurally unrelated drugs has remained difficult to decipher. However, the recent functional expression of this group of proteins in the membrane of secretory vesicles from yeast mutants has allowed the systematic analysis of the parameters of drug transport by this protein. Proposed mechanisms of action of P-glycoprotein are discussed in this review by Stephan Ruetz and Philippe Gros.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Cloning, sequencing and expression of the L5, L21, L27a, L28, S5, S9, S10 and S29 human ribosomal protein mRNAs.

During systematic analysis of the mRNAs expressed in a human colorectal carcinoma with the aim of evidencing new makers of the disease (Frigerio et al. (1995), in press), we isolated several clones corresponding to homologs of rat ribosomal protein mRNAs L5, L21, L27a, L28, S5, S9, S10 and S29. Because expression of several mRNAs encoding ribosomal proteins was found strongly altered during colorectal carcinogenesis, sequence of these transcripts, not previously described in human, was completed and their expression analyzed. Northern blot analysis of RNAs extracted from colorectal cancer and ajdacent normal tissue from 6 patients revealed in all of them perturbations of expression in cancer, compared to normal. No correlation could however be made between the level of expression and the severity of the disease. Yet, abnormal patterns with additional larger transcripts were observed in some patients for rpL5, rpL28 and rpS10.

Amino Acid Sequence↗
PubMed1994

Left ventricular performance in patients with normal coronary arteries: hemodynamic characteristics and clinical follow-up.

Of 111 patients with normal coronary angiograms, 68 patients had elevated left-ventricular end diastolic pressure and 'low-normal' ejection fraction (Group I) while the other 43 patients had normal left ventricular end diastolic pressure and 'high normal' ejection fractions (Group II). Although the number of patients was too small for meaningful statistical analysis, systematically a higher percentage of patients with diabetes mellitus, hypertension, hypercholesterolemia and smoking history was found in Group I. In contrast to the patients in Group II, patients in Group I tended to have more angina and ischemic events.

Blood Pressure↗
PubMed1985

Developmental assessment of spinal cord and cortical evoked potentials after tibial nerve stimulation: effects of age and stature on normative data during childhood.

Somesthetic information from lower extremities is processed by cerebral cortex after traversing the sensory pathways of peripheral nerve, spinal cord, brain-stem and thalamus. Clinical utility of somatosensory evoked potentials (SSEPs) during human development requires systematic analysis of normative data acquired during various stages of body growth and nervous system maturation. Accordingly, SSEPs after tibial nerve stimulation were studied in 32 normal awake children (1-8 years old) and compared with values obtained in young adults (18-40 years old). Potentials were recorded from the tibial nerve (N5), first lumbar spinous process (N14), seventh cervical spinous process (N20) and from the scalp, 2 cm behind the vertex (P28). In all children studied, the N5, N14 and N20 latencies were positively correlated with age and height yielding a predictive nomogram. An extremely variable electropositive cortical SSEP was recorded from Cz' which did not show a highly predictable linear relationship in association with a relatively poor correlation coefficient for height and age. It may be concluded that between 1 and 8 years of normal postnatal development, latencies reflecting peripheral nerve and lumbar spinal cord vary directly with height and age and can be represented by a simple cable model of a lengthening myelinated pathway. In contrast, the latency of the cortical SSEP reflects asynchronous maturation of elongating polysynaptic pathways and apparently requires a more complex model for prediction in order to enhance its clinical utility.

Adolescent↗