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At least 307 records · Page 17Linked to original sources

Cancer in Kampala, Uganda, in 1989-91: changes in incidence in the era of AIDS.

Re-establishment of the cancer registry in Kyadondo County, Uganda, has allowed estimation of incidence rates for the period September 1989 to December 1991. The results are compared with earlier data from the same area, and from other African cancer registries. The most striking feature is the emergence of Kaposi's sarcoma as the leading cancer in males (almost half of all registered cases) and the second most frequent (17.9%) in females. This parallels the evolution of the epidemic of AIDS. There were also marked increases in the incidence of both oesophageal and prostatic carcinoma, while the incidence of cancer of the penis and the urinary bladder declined, possibly as a result of improved standards of hygiene. In females, the incidence of cancer of the cervix has more than doubled since the 1950s, and is now among the highest recorded in the African continent.

Acquired Immunodeficiency Syndrome↗

Adrenal medulla in neural grafting and neural plasticity.

The recent history of neural transplantation using the adrenal medulla parallels an evolution in our thinking about neural grafting as a therapeutic approach to treat neurodegenerative diseases such as Parkinson's disease. Initially, neural grafting was an approach to study development and regeneration. With the discovery that adrenal chromaffin cell grafts would ameliorate some of the motor deficits associated with the loss of striatal dopamine, adrenal grafts were used to provide dopamine to the dopamine-depleted striatum. However, subsequent studies showed poor chromaffin cell survival unless trophic factors were present at the site of transplantation. These experiments lead to the appreciation of the complex interactions between neurotrophic factors, inflammatory cytokines, the grafted tissue, and the host brain's response. Thus, we find ourselves again using neural transplantation as an approach to help us better understand central nervous system plasticity and the features this plasticity shares in common with development and regeneration.

Adrenal Medulla↗

Murine models of Sjögren's syndrome.

Autoimmune MRL/lpr, MRL/+, and NZB/W mice all develop lacrimal gland inflammatory lesions, which consist of focal mononuclear inflammatory cell infiltrates. Each strain has a different immunocytochemical profile, which appears to be related to the underlying immunologic defects present in that mouse. The appearance of these lesions parallels the evolution of the systemic autoimmune disease. The lesions are dynamic over time with the early appearance of CD4+ T cells (helper T cells) for each strain. Subsequently, there is an accumulation of B cells over time in MRL/+ and NZB/W mice. In the two more rapidly evolving mouse models, MRL/lpr and NZB/W, there is a progressive decline in the percentage of CD8+ cells. Conversely, in the slowly evolving MRL/+ lacrimal gland lesions, there is a persistent and unchanging percentage of CD8+ T cells (suppressor/cytotoxic T cells). Autoimmune mice provide models for the human disorder Sjögren's syndrome and a mechanism for better understanding the immunopathogenesis of autoimmune lacrimal gland disease.

Animals↗

Short-term neurophysiological monitoring in multiple sclerosis bouts. Evaluation of steroid treatment.

Visual (VEP) and brainstem auditory (BAEP) evoked potentials (EP) were recorded in 21 multiple sclerosis (MS) patients in acute relapse before and after steroid treatment. VEPs were abnormal in 14/21 patients and BAEPs in 10/21 patients before treatment. In 4 patients with acute optic neuritis (ON), an improvement of VEPs paralleled clinical evolution in 3 cases. Substantial and contrasting changes in VEPs or BAEPs, with no clinical counterpart, were related to a spontaneous fluctuation of EPs in acute relapses of MS. These changes suggest frequent subclinical (multifocal and, possibly, sequential) central nervous system involvement in MS bouts. Group analysis showed nonsignificant changes in EP parameters before and after treatment. Our results indicate that evoked potentials (EPs) are of limited value for monitoring the short-term effect of steroid treatment in MS in bouts.

Adult↗

Evolutionary analysis of the ErbB receptor and ligand families.

We have compared all available deduced protein sequences of the ErbB family of receptors and their ligands. Analysis of the aligned sequences of the receptors indicates that there are some differences in the receptors that are specific to invertebrates. In addition, comparison of the vertebrate ErbB receptors suggest that a gene duplication event generated two ancestral receptors, the ErbB3/ErbB4 precursor and the ErbB1/ErbB2 precursor. Subsequent gene duplications of these precursors generated the four receptors present in mammals. Analysis of the sequences for the known ligands of the ErbB receptors suggests that the vertebrate ligands segregate into the ErbB1 ligands and the ErbB3/ErbB4 ligands, paralleling the evolution of the receptors; however, it is difficult to ascertain any correlation between the invertebrate and the vertebrate ligands. Even though ErbB3 is kinase-impaired, there is significant conservation of the kinase domain within the vertebrate lineage (human, rat, and F. rubripes), suggesting some function for this domain other than kinase activity, such as mediating protein-protein interactions that are involved in receptor dimerization and/or activation of the kinase domain of the heterodimerization partner. To date, no ligand for ErbB2 has been identified, and comparison of the extracellular domains of ErbB2 reveals two regions that are not conserved across the mammalian species. These two regions of divergence align with sequences in ErbB1 that have been shown to be proximal to the amino-terminus and to the carboxyl-terminal region, respectively, of bound EGF. Further, one of these regions contains an insertion, relative to the other members of the mammalian ErbB family, which might affect the ligand binding site and provide a structural basis for this receptor's apparent inability to bind ligand independently.

Amino Acid Sequence↗

Infectious antecedent of immunoblastic lymphoma. Progressive immunosuppression in a patient with lymphogranuloma venereum.

Angioimmunoblastic lymphadenopathy is a nonmalignant disease of unknown etiology often progressing to immunoblastic lymphoma. Immunologic deficiency is evident in these patients as well as in those with various infections found in association with the acquired immune deficiency syndrome (AIDS). This report describes a previously healthy young woman in whom angioimmunoblastic lymphadenopathy developed in association with lymphogranuloma venereum, with progressive loss of immunologic competence. This deterioration paralleled the evolution of angioimmunoblastic lymphadenopathy into a rapidly fatal immunoblastic lymphoma.

Adult↗

Resistance and the control of sheep ectoparasites.

For about 100 years Australian woolgrowers have used a variety of chemicals to control blowflies, lice and other ectoparasites of sheep. While the chemicals have changed considerably the application technology has not changed very much at all. Chemicals registered for use on sheep have paralleled the evolution of synthetic insecticides with the unfortunate consequence of the development of resistance in the Australian sheep blowfly, Lucilia cuprina, following closely behind. Organochlorine (dieldrin) resistance peaked at about 70% in 1958 when unacceptable residues in meat and wool forced their withdrawal. Organophosphate (OP) resistance appeared in 1965. With no alternative insecticide classes until 1979, OP resistance reached near fixation levels by the early 1970s and has remained unchanged. OP resistance has reduced the protection period from over 16 weeks to about 6 weeks. Moreover, resistance has decreased the effectiveness of many flystrike dressings to unacceptably low levels. OPs are still very effective against sheep body lice, Bovicola ovis but control is hampered by inadequate application via plunge or shower dipping. Synthetic pyrethroid (SP) pour-on products were released in 1981 but resistance developed by 1985 and many woolgrowers were unable to eradicate lice with pour-on products. Highest Resistance Factors at this time were only about 26 x but this was sufficient to prevent pour-ons working efficiently. By 1991 a population from Hartley in NSW was found to be 642 x resistant to cypermethrin with side-resistance conferred to the other SPs. SP resistance was partially suppresible by piperonyl butoxide but field trials suggested that the resulting improvement in efficacy was not sufficient to be commercially attractive. OPs remain very effective if applied correctly and the release of ivermectin and 2 benzoylphenyl urea products significantly improves the prospects for resistance management. However the increasing environmental concern about the persistence of chemical residues in wool has stimulated interest in biological control of sheep lice by Bacillus thuringiensis.

Animals↗

Isotype, distribution and target analysis of lymphocyte reactive antibodies in patients with human immunodeficiency virus infection.

Anti-lymphocyte (ALA) antibodies were investigated by using both microcytotoxicity and immunofluorescence analyses in 87 subjects with different clinical features of human immunodeficiency virus (HIV) infection. A similar mean percentage of killing in microcytotoxicity assays using heterologous lymphocytes as cellular target was recorded in four groups of patients, including 36 HIV-seropositive asymptomatic subjects, 34 patients with HIV-induced lymphadenopathy syndrome (LAS), 13 with acquired immunodeficiency syndrome (AIDS)-related complex (ARC), and 4 patients with the full-blown AIDS. Conversely, an increasing percentage of ALA-positive subjects paralleled the evolution of the HIV infection. The majority of ALA were IgM isotype with a significant reactivity against T cells. This specificity was indifferently directed to CD3+, CD4+, and CD8+ lymphocytes. In additional experiments employing enzymatic digestion of lymphocyte membrane antigens, we demonstrated that CD4 and CD8 receptors were digested by the pronase, whereas CD3 molecules were highly resistant. Subsequent flow cytometry analyses using these pronase-digested T cells showed that reactivity of ALA for their target was unchanged. Our data suggest that antigenic specificities of ALA in HIV infection are resistant to pronase treatment and are not related to CD4 and CD8 molecules.

Antigens, Differentiation, T-Lymphocyte↗

Adaptational response in transcription factors during development of myocardial hypertrophy.

Cardiac hypertrophy is characterized, among others, by the molecular events which selectively activate the expression of genes for contractile proteins within individual myocardial cells. As such, myosin light chain 2 (MLC-2), which is upregulated in the hypertrophic state in both rat and human, serves as a marker for hypertrophy. In an attempt to investigate the gene regulatory mechanisms of this phenomenon, we tested the hypothesis that certain transcription factors are directly involved in the development of cardiac hypertrophy by demonstrating the presence of cardiac tissue-specific regulatory elements in the 5'-flanking region of the MLC-2 promoter and testing them in the gel mobility shift assay for their binding activity to nuclear proteins from hypertrophied and normal cardiac tissue. In nuclear extracts from the ventricular tissues of the spontaneously hypertensive rat (SHR), distinctive changes in two families of activator proteins, the A/T-rich DNA-binding transcription factors, myocyte enhancer factor (MEF-2) and CArG-binding factor, manifested in a developmentally dictated manner paralleling the evolution of cardiac hypertrophy in these animals. Extracts isolated from brains and skeletal muscle tissues from the same animals did not exhibit the changes in binding activity. Also, the changes were not apparent when a distal negative regulatory element (CSS), which confers cardiac-specific expression, was tested in gel mobility shift assays. The ubiquitous TATA-binding proteins remained unchanged in comparing SHR with the control strain WKY in the same assay. These data support the notion that the expression of specific transcription factors is modulated in response to hypertrophy related signals which execute changes at the gene level effecting the enrichment of certain contractile proteins in an effort discrete and estranged from the basal transcription machinery.

Adaptation, Physiological↗

Deletions of 17p are associated with transition from early to advanced colorectal cancer.

Several chromosome defects parallel morphologic evolution in colorectal tumor progression. Allelic losses in the short arm of chromosome 17, the majority encompassing the 17p13.3 band, have been found in advanced cancer in the absence of TP53 mutations, suggesting that loss of genes in this chromosome region is relevant for tumorigenesis. The aim of this study was to investigate 17p13.3 deletions throughout the colorectal tumor progression using two-color fluorescence in situ hybridization. Histologic sections from 20 colorectal adenomas containing early invasive carcinoma were analyzed by interphase fluorescence in situ hybridization using a centromeric probe for chromosome 17 simultaneously with a subtelomeric probe mapping to the 17p13.3 band. Separate evaluation was made for sectors corresponding to adenoma tissue with low-grade dysplasia, high-grade dysplasia, and early cancer. The same technique was also used in 20 cases of advanced adenocarcinoma of the large bowel. Loss of one centromeric signal was observed in 20, 40, 50, and 10% of low-grade dysplasia, high-grade dysplasia, early cancer, and advanced cancer, respectively (P<0.02 early vs. advanced cancer). Subtelomeric 17p deletions were seen in 60% of advanced cancer and in 15% of early cancer (P<0.01). These findings indicate that loss of genes from the 17p13.3 chromosome region may play an important role in sustaining the transition from early to advanced cancer in colorectal tumor progression.

Adenocarcinoma↗

Glial reaction to volkensin-induced selective degeneration of central neurons.

Volkensin, a highly toxic protein retrogradely transported through axons, was used to target primary neuronal death in brainstem precerebellar relays after injection in the cerebellar cortex of rats. The reaction of astrocytes and microglia was studied with immunohistochemistry in the inferior olivary and pontine nuclei from 6 h to 14 days. Neurodegenerative features were evident since the first hours, especially in the pontine nuclei, and neuronal loss reached a plateau at 7 days in the inferior olive and at 10 days in the pons. Astrocytic activation, revealed by glial fibrillary acidic protein immunoreactivity, was concomitant with early signs of neuronal death and gradually increased. Microglia activation, revealed by OX-42 immunoreactivity, was evident at 2 days and became rapidly intense in precerebellar relays. At 1 week, marked ED-1 immunoreactivity also revealed phagocytic features of microglia, which persisted during the second week. In addition, major histocompatibility complex antigens (MHC) class I and II were induced in cells exhibiting microglial features. In the inferior olive, MHC I immunoreactivity was evident since 4 days and persisted at 14 days, whereas MHC II induction was intense at 7 days and subsided at 2 weeks. In the pontine nuclei high expression of both MHC antigens persisted instead at 14 days, probably reflecting the progression of neuronal death. Thus, targeted lethal injury of central neurons elicited prompt activation of both astrocytes and microglia; the marked microglia activation resulted in phagocytic features and immunophenotypic changes, with a temporal regulation that paralleled the evolution of neurodegenerative phenomena.

Animals↗

Effects of disulfiram on the amphetamine-induced behavioral syndrome in the cat as a model of psychosis.

We have previously reported that, from a phenomenological standpoint, the behavioral manifestations of cats chronically intoxicated with amphetamine parallel the evolution of the paranoid psychosis induced by the drug in humans. However, certain manifestations in the cat, such as frozen postures, disjunctive behaviors and postures, cataleptic-like phenomena, obstinate progression, loss of righting reflex and pupillary changes, did not appear to be consistent with the phenomenology of the paranoid psychosis. Since treatment of schizophrenic patients with disulfiram, an inhibitor of norepinephrine synthesis that acts at the level of the enzyme dopamine beta-hydroxylase, thereby leading to increased dopamine concentrations, had been found to profoundly exaggerate psychotic symptomatology, amphetamine behavioral syndrome in the cat as it is modified by pretreatment with disulfiram. Following such pretreatment, a faster development of certain end-stage components of the amphetamine syndrome was obtained. Thus, on the first day, development of a Reactive attitude and of more prominent behavioral disjunction occurred with the combined drug administration as compared with amphetamine alone. In contrast with the facilitation of these behaviors was the absence of dyskinesias and hyperreflexia on that day. Stereotyped behavior, loss of motor initiative and hyperkinetic activity were markedly enhanced and appeared with a shorter latency period on subsequent days of the intoxication cycle. Loss of righting reflex was an early manifestation in these animals. During the later days, the particularly high level of compulsive activity was evident from the occurrence of an obstinate progression syndrome and the performance of stereotyped movements of the head in the presence of a crucifixion posture. In general, modification of the amphetamine effects on behavior was in a direction consistent with comparable features in experimental catatonia and the catatonic form of schizophrenia. The need to integrate such phenomena in any amphetamine model of psychosis is stressed and analogies are drawn with similar features reported in animals treated with bulbocapnine or other psychotogenic compounds and with symptoms of human amphetamine psychosis and schizophrenia.

Animals↗

Parallel genetic basis for repeated evolution of armor loss in Alaskan threespine stickleback populations.

Most adaptation is thought to occur through the fixation of numerous alleles at many different loci. Consequently, the independent evolution of similar phenotypes is predicted to occur through different genetic mechanisms. The genetic basis of adaptation is still largely unknown, however, and it is unclear whether adaptation to new environments utilizes ubiquitous small-effect polygenic variation or large-effect alleles at a small number of loci. To address this question, we examined the genetic basis of bony armor loss in three freshwater populations of Alaskan threespine stickleback, Gasterosteus aculeatus, that evolved from fully armored anadromous populations in the last 14,000 years. Crosses between complete-armor and low-armor populations revealed that a single Mendelian factor governed the formation of all but the most anterior lateral plates, and another independently segregating factor largely determined pelvic armor. Genetic mapping localized the Mendelian genes to different chromosomal regions, and crosses among these same three widely separated populations showed that both bony plates and pelvic armor failed to fully complement, implicating the same Mendelian armor reduction genes. Thus, rapid and repeated armor loss in Alaskan stickleback populations appears to be occurring through the fixation of large-effect variants in the same genes.

Animals↗

The olfactory receptor gene repertoire in primates and mouse: evidence for reduction of the functional fraction in primates.

Olfactory receptors (ORs) located in the cell membrane of olfactory sensory neurons of the nasal epithelium are responsible for odor detection by binding specific odorant ligands. Primates are thought to have a reduced sense of smell (microsmatic) with respect to other mammals such as dogs or rodents. We have previously demonstrated that over 70% of the human OR genes have become nonfunctional pseudogenes, leading us to hypothesize that the reduced sense of smell could correlate with the loss of functional genes. To extend these results, we sampled the OR gene repertoire of 10 primate species, from prosimian lemur to human, in addition to mouse. About 221 previously unidentified primate sequences and 33 mouse sequences were analyzed. These sequences encode ORs distributed in seven families and 56 subfamilies. Analysis showed a high fraction ( approximately 50% on average) of pseudogenes in hominoids. In contrast, only approximately 27% of OR genes are pseudogenes in Old World monkeys, and New World monkeys are almost free of pseudogenes. The prosimian branch seems to have evolved differently from the other primates and has approximately 37% pseudogene content. No pseudogenes were found in mouse. With the exception of New World monkeys, we demonstrate that primates have a high fraction of OR pseudogenes compared with mouse. We hypothesize that under relaxed selective constraints, primates would have progressively accumulated pseudogenes with the highest level seen in hominoids. The fraction of pseudogenes in the OR gene repertoire could parallel the evolution of the olfactory sensory function.

Animals↗

Epidemiology of infections due to Pseudomonas aeruginosa.

Pseudomonas aeruginosa is responsible for an increasing proportion of infections acquired in the modern hospital setting. It accounts for 8.5% of all nosocomial infections and has an attack rate of 36 infections per 10,000 hospital discharges. P. aeruginosa represents the single most frequently isolated pathogen in patients with nosocomial pneumonia and burn-wound infections. The organism's bioepidemiology is linked to its ability to thrive in marginal econiches, and its ascendency as a nosocomial pathogen parallels the evolution of high-technology intensive care units, the large numbers of immunocompromised patients, and the liberal use of antibiotics. The reservoirs and modes of transmission for this organism are reviewed along with recent studies aimed at the prevention of both colonization and infection by this organism.

Cross Infection↗

Pattern of morphological diversification in the Leptocarabus ground beetles (Coleoptera: Carabidae) as deduced from mitochondrial ND5 gene and nuclear 28S rDNA sequences.

Most of the mitochondrial NADH dehydrogenase subunit 5 (ND5) gene and a part of nuclear 28S ribosomal RNA gene were sequenced for 14 species of ground beetles belonging to the genus Leptocarabus. In both the ND5 and the 28S rDNA phylogenetic trees of Leptocarabus, three major lineages were recognized: (1) L. marcilhaci/L. yokoael/Leptocarabus sp. from China, (2) L. koreanus/L. truncaticollis/L. seishinensis/L. semiopacus/L. canaliculatus/L. kurilensis from the northern Eurasian continent including Korea and Hokkaido, Japan, and (3) all of the Japanese species except L. kurilensis. Clustering of the species in the trees is largely linked to their geographic distribution and does not correlate with morphological characters. The species belonging to different species groups are clustered in the same lineages, and those in the same species group are scattered among the different lineages. One of the possible interpretations of the present results would be that morphological transformations independently took place in the different lineages, sometimes with accompanying parallel morphological evolution, resulting in the occurrence of the morphological species belonging to the same species group (= type) in the different lineages.

Animals↗

Complete congruence between morphological and rbcL-based molecular phylogenies in birches and related species (Betulaceae).

Estimations of phylogenies from morphological and molecular data often show contrasting results. We compared morphological and molecular phylogenies in an ancient family of woody dicots, the Betulaceae (birch family). The phylogeny of the family was estimated from parsimony analysis of morphological characters in the genera Alnus, Betula, Carpinus, Corylus, Ostrya, and Ostryopsis and from parsimony and distance-matrix analyses of DNA sequences of the chloroplast gene encoding the large subunit of ribulose-1,5-biphosphate carboxylase (rbcL) in the genera Alnus, Betula, Carpinus, Corylus, and Ostrya and in two outgroups, Quercus and Liquidambar. The topologies obtained by the different methods were completely congruent, and bootstrapping strongly supported the division of the family Betulaceae into two major clades, Betuleae (Alnus and Betula) and Coryleae (other members). Only slightly more homoplasy was present in the rbcL sequence data set than in the morphological set. Relative-rate tests indicated that the Coryleae clade had a faster rate of rbcL evolution than did the Betuleae clade. Heterogeneity of rates of morphological evolution also paralleled those for rbcL.

Base Sequence↗