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p53 gene analysis in childhood B non-Hodgkin's lymphoma.

CONTEXT: Mutations or deletions in the tumor-suppressor gene p53 are among the commonest genetic changes found in human neoplasms including breast, lung and bowel cancers. In hematological malignancies, p53 is most often mutated in Burkitt's lymphoma, with p53 mutations present in 30 to 40% of tumor samples and in 70% of cell lines. OBJECTIVE: To analyze the p53 gene alterations in child patients with B non-Hodgkin's lymphoma. DESIGN: Descriptive study. SETTING: Tertiary oncology care center. PARTICIPANTS: The study investigated 12 patients with childhood B non-Hodgkin's lymphoma (Burkitt's lymphoma). Screening for p53 mutations was done by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis of exon 5 to 8/9 of the gene. RESULTS: Abnormal polymerase chain reaction-single strand conformational polymorphism migration pattern was observed in 4 patients (33.3%), one on exon 6 and three on exon 7. Positive cases included 2 patients who died from disease. CONCLUSION: These preliminary results suggest that p53 mutations are quite frequent in children with Burkitt's lymphoma and may play a role in lymphoma genesis or disease progression.

Burkitt Lymphoma↗

Genomic diversity and prevalence of Rotavirus in cow and buffalo calves in northern India.

Faecal samples were collected from seventy-eight diarrhoeic cow and buffalo calves between November 1998 and February 1999 to study the genomic diversity and prevalence of Rotavirus infection by ribonucleic acid polyacrylamide gel electrophoresis (RNA-PAGE) and enzyme-linked immunosorbent assay (ELISA). In the organised dairy farm (where daily production and health records were maintained), the overall prevalence of infection with Rotavirus, recorded by RNA-PAGE and ELISA, was 27.02% (10/37) in both cow and buffalo calves. In unorganised dairy herds (where no production or health records were maintained), RNA-PAGE and ELISA detected infection with Rotavirus in 26.8% (11/41) of cow and 19.5% (8/41) of buffalo calves. Five distinct electropherotypes were found to circulate in cow and buffalo calves. All were short electropherotypes except the single long electropherotype observed in a buffalo calf in an unorganised dairy herd. Some differences in RNA migration pattern were observed when these electropherotypes were compared with the neonatal calf diarrhoea virus strain of Rotavirus. Some electropherotypes were restricted to one farm while others were found in both organised and unorganised dairy herds and in both cow and buffalo calves.

Age Factors↗

An outbreak of sheep pox on a sheep breeding farm in Jammu, India.

An outbreak of sheep pox occurred in December 2001 on a sheep breeding farm in Jammu, India. The farm maintains three exotic breeds of sheep, i.e. American Merino, Rambouillet and Australian cross. The disease agent was confirmed as sheep pox virus by clinical and post-mortem examination as well as laboratory testing. Typical pock lesions were dispersed over the body of the affected animals with nodular lesions observed in the lung tissue of the dead animals. Sheep pox virus antigen and antibody were detected in infected tissue and convalescent sera, respectively, with serological tests. Viral deoxyribonucleic acid was extracted from the infected tissue and amplified using a diagnostic polymerase chain reaction. Sheep of the Rambouillet breed were found to be most susceptible to infection with morbidity and mortality rates of 26.9% and 8.3%, respectively. Morbidity and mortality rates in the entire flock were 18.4% and 6.3%, respectively. The grazing and migration pattern indicates that the disease was probably introduced to the farm by local sheep.

Animals↗

Manpower planning for nurse personnel.

A technique is described which can be applied to manpower planning for nurse personnel at a state or regional level. An iterative process explores the implications of alternative planning policy decision strategies intended to balance manpower supply and requirements. Impacts of the following policy alternatives are estimated: scale of operations of education institutions; interstate migration patterns; labor force participation rates; and job design of licensed practical nurse (LPN) and registered nurse (RN) positions.

Nurses↗

Individual health status and racial minority concentration in US states and counties.

OBJECTIVES: We examined whether the positive association between mortality rates and racial minority concentration documented in ecological studies would be found for health status after control for race/ethnicity, socioeconomic status, and region of residence. METHODS: We estimated least squares and probit models using aggregate and individual health status data from the 1995, 1997, and 1999 versions of the Current Population Survey merged with data from the US Bureau of the Census regarding state- and county-level racial minority concentration. RESULTS: Except in the case of older Whites, racial minority concentration was not associated with health status after control for individual characteristics and fixed regional factors. CONCLUSIONS: Racial minority concentration may not be a determinant of individual health; differential migration patterns may explain the anomalous result for older Whites.

Adult↗

Epidemic in the war zone: AIDS and community survival in New York City.

The characteristics and consequences of the AIDS/HIV epidemic in New York City are examined, with special attention to its impact on inner-city communities. The high numbers of AIDS cases are the source of increasing stress on public and community treatment and family and neighborhood networks of support. As the epidemic deepens (8 to 10 thousand new cases per year are expected by 1992) these resources, already weakened by years of underfunding, are becoming overwhelmed and are in danger of collapse. The high rates of HIV infection in these communities (5 to 20 percent of adults aged 25 to 45) and their linkage to widespread drug use prefigure the development of endemic levels in several population subgroups, with substantial risk of heterosexual spread. Simultaneously, there is a steady diffusion of infection to adjacent urban areas and, via migration patterns, to localities quite distant from New York City (e.g., Puerto Rico). Some hope can be found in the advent of more effective methods of early intervention for presymptomatic HIV infection. These offer an opportunity for combining clinical care with public health strategies that may restrict the spread of HIV while providing humane care for large numbers of people with AIDS and support for their families.

Acquired Immunodeficiency Syndrome↗

Lymph node T-cells do not optimally transfer diabetes in NOD mice.

The nonobese diabetic mouse in a model of spontaneous development of autoimmune type I diabetes. The disease can be induced in young, irradiated recipients by injecting splenic T-cells from diabetic donors. The adoptive transfer of diabetes requires the presence of both CD4+ and CD8+ splenic T-cell subsets. To test whether diabetogenic cells distribute in other lymphoid organs of diabetic mice, we first analyzed lymph node cells. Lymph node cells were much less efficient in transferring diabetes than splenocytes. This inefficacious transfer was not attributable to the absence of hematopoietic precursors or a lack of macrophages. Lymph node cells did not protect from the transfer of diabetes by splenocytes, indicating the absence of suppressor cells. Although CD8+ lymph node T-cells seemed functionally comparable to CD8+ splenocytes, CD4+ lymph node T-cells failed to cooperate with CD8+ splenocytes to transfer diabetes. Our study suggests that diabetogenic cells are not evenly distributed in the different lymphoid organs. This may reflect a differential migration pattern of pathogenic T-cells in this animal model.

Animals↗

Molecular analysis of porphobilinogen (PBG) deaminase gene mutations in acute intermittent porphyria: first study in patients of Slavic origin.

Acute intermittent porphyria (AIP) is an autosomally dominant inherited metabolic disorders caused by decreased activity of porphobilinogen deaminase, the third enzyme in the human heme biosynthetic pathway. We report here the first mutations in the human porphobilinogen deaminase gene in seven unrelated patients from the Czech and Slovak Republics with acute intermittent porphyria. We used denaturing gradient gel electrophoresis to screen all 15 exons and exon/intron boundaries of the porphobilinogen deaminase gene. Polymerase chain reaction products of abnormal migration patterns were subjected to direct sequencing to identify the causative mutations. Thus we revealed four novel mutations and three which have been previously described. Of the four novel mutations, two were mis-sense (G24S, V267M), one was a single base insertion (158insA) that produced a stop codon 12 codons downstream, and one was a single base substitution in intron 12 (771 + 1) resulting in a splicing defect. The three previously detected mutations were mis-sense mutations (R26C, R26H, G111R). These results suggest a high allelic heterogeneity in Czech and Slovak patients.

Aminolevulinic Acid↗

S-antigen in non ocular tissues.

S-antigen has been considered a specific protein of photoreactive cells by immunohistochemical criteria. It was observed in the retina and pineal gland of all examined vertebrates as well as in photoreceptors of invertebrates, but not currently in other organs. However, contrary to pineal cells of poikilotherms and birds which are true or modified photoreceptors, mammalian pinealocytes are not photosensitive. Recent experiments demonstrated that S-antigen-like proteins are present in low amount in many other cells in the body. These proteins are characterized by the same migration pattern (the same molecular weight) as retinal S-antigen in SDS-electrophoresis and by their immunoreactivity with a panel of monoclonal and polyclonal antibodies to S-antigen. These cells are not photosensitive, but are controlled by beta adrenergic, G-protein mediated adenylate cyclase system, a transduction system that shares many structural and functional homologies with visual transduction. S-antigen (arrestin) plays a regulatory role in phototransduction in rods by desensitizing rhodopsin. In the mammalian pineal and in other cells or tissues, S-antigen, or a family of structurally related proteins, could similarly be involved in the regulation of chemical signal transduction. Whether any systemic pathology is associated with uveoretinitis and pinealitis after S-antigen immunization deserves further investigations.

Animals↗

Structural properties of Type I collagen isolated from chickens with scoliosis.

This study examines biochemically the Type I collagen isolated from skin of chickens that develop idiopathic scoliosis. Previous studies indicate a defect in collagen exists in these chickens. Alpha 1 (I) and alpha 2 chains were separated by gel filtration and carboxymethyl cellulose column chromatography and were then subjected to the analytical techniques of sodium dodecyl sulfate gel electrophoresis, Staphylococcus aureus V8 protease digestion, cyanogen bromide peptide mapping and amino acid analyses. In all categories, the scoliotic alpha 1 (I) and alpha 2 chains were identical to alpha chains isolated from normal chickens. These data suggest that the altered properties of collagen solubility and connective tissue stress relaxation seen in these scoliotic chickens are not a manifestation of an altered primary structure of the alpha chains or post-translational modification affecting chromatographic elution profiles or electrophoretic migration patterns.

Amino Acids↗

Precursor matrix proteins in the uterine fluid change with stages of eggshell formation in hens.

Organic constituents of the uterine fluid, the acellular milieu in which the eggshell is mineralized, were biochemically characterized at initial, mid and final stages of shell calcification in hens. The electrophoretic protein profiles changed at the different stages of shell mineralization. Two major bands (80-kDa and 43-kDa glycoproteins) with calcium affinity were specific to the initial stage. Four protein bands of 180, 150, 116 and 32 kDa, present at the phase of rapid shell formation, coprecipitated with calcium carbonate in vitro. At this stage were also present a calcium-binding glycoprotein of 36-kDa and a 20-kDa protein. Uterine fluid of the final stage was characterized by a darker intensity of the 66-kDa band, which showed calcium-binding ability and by the presence of three additional proteins (72, 13 and 6 kDa). At least seven bands of the uterine fluid showed similar migration patterns to those of eggshell extracts. Western blotting with ovocleidin and ovalbumin antisera demonstrated the presence of these matrix proteins in uterine fluid collected at initial and mid phase, respectively. Total uterine fluid collected at the end of calcification and dialyzed uterine fluid from the various stages delayed the rate of calcium precipitation in vitro. These observations demonstrate the presence of precursors of eggshell matrix in the uterine fluid and support the hypothesis of their involvement in the process of eggshell mineralization.

Animals↗

A novel haplotype of the endogenous retrovirus, HRES-1, in patients with multiple sclerosis and healthy individuals.

In this study we searched for genetic variation in a segment of the human endogenous retrovirus, HRES-1, which encodes a potential autoantigen of 28 kDa. The purpose was to further investigate a possible association between this endogenous retrovirus and multiple sclerosis (MS). Fragments amplified from the HRES-1 region in question were subjected to single strand conformational analysis (SSCP analysis) and sequencing if the SSCP migration pattern suggested presence of polymorphisms. Using this approach a synonymous G --> C substitution, creating an NciI site, was found. Our sequence data also revealed an additional nucleotide in the region encoding the 28-kDa protein, i.e. a nucleotide not present in the first published sequence. This finding has implications for future studies of the 28-kDa HRES-1 protein since the additional nucleotide changes the reading frame of this protein. The detection of the Nci polymorphism allowed us to define a novel haplotype of HRES-1 distinct from the three previously known HRES-1 haplotypes. On comparison of the distribution of these four haplotypes in MS patients and healthy individuals we found a statistically significant difference (P = 0.03) but the contribution from the novel haplotype to this was modest.

Alleles↗

Molecular evidence of clonal Vibrio parahaemolyticus pandemic strains.

The upsurge in worldwide incidence of Vibrio parahaemolyticus infection in the last 5 years has been attributed to the recent appearance of three serotypes with pandemic potential: O3:K6, O4:K68, and O1:K untypeable (KUT). Thirty-five strains of these serotypes, isolated from different countries over 4 years, were characterized by ribotyping and pulsed-field gel electrophoresis to determine their origin. The ribotypes of the strains of these serotypes were indistinguishable, except for a Japanese tdh- negative O3:K6 strain and a U.S. clinical O3:K6 isolate, which had slightly different profiles. The migration patterns of the NotI-digest of the total DNA of the strains were similar, and only slight variations were observed between the serotypes. By contrast, the O3:K6 and O1:KUT strains isolated before 1995 and strains of other serotypes had markedly different profiles. The O4:K68 and O1:KUT strains most likely originated from the pandemic O3:K6 clone.

Blotting, Southern↗

There is no evidence that the SDHB gene is involved in neuroblastoma development.

Neuroblastoma and pheochromocytoma have the same embryonal origin. They originate from neural crest cells, and they usually affect suprarenal glands. The SDHB gene encodes the B subunit of succinate dehydrogenase, a protein implicated in the electron transport chain and Krebs cycle. Some mutations have been described in this gene in pheochromocytoma, and this gene could be an appropriate candidate for its study in neuroblastoma given its localization in 1p35-36. The aim of this study was to analyze neuroblastoma tumors in order to assess a possible implication of this gene in neuroblastoma development. We studied 28 neuroblastoma tumor samples from different stages. Mutation research in genomic DNA was carried out after individual amplification of each of the eight SDHB exons by SSCP analysis and sequencing of those samples with migration pattern variants. No variant was found except for three polymorphisms in four neuroblastoma samples. The first polymorphism was a synonymous A-->C change in the third position of codon 6 (exon 1). The other two polymorphisms were a TTC insert at the 5' flanking intron sequence of exon 5 in a stretch of seven TTC repeats. Upon the basis of posterior microsatellite instability and hypermethylation promoter studies, which were not significant, we can conclude that the SDHB gene, a positional candidate gene, is unlikely to be related to either initiation or tumoral progression in neuroblastoma.

DNA Mutational Analysis↗

Verbal and visuospatial short-term memory in children: evidence for common and distinct mechanisms.

This study was designed to identify whether verbal and visuospatial short-term memory performance in children is served by common or distinct mechanisms. Five- and 8-year-old children were tested on their verbal recall of spoken letter names and digits, and on their recall of tapped sequences of blocks. The performance of the children on the verbal and visuospatial serial recall tasks was largely unrelated, extending evidence for dissociable memory systems found in adults. Detailed characteristics of recall, such as serial position functions, migration patterns, and distribution of error types, were similar in the tasks requiring recall of letters and of blocks, although order errors predominated in the block but not the letter recall task for the older children. These results appear to reflect the application of common processes specialized for the extraction of serial order information from the phonological and visuospatial components of short-term memory.

Adult↗

Role of the neural crest in anterior segment development and disease.

Certain eye and associated systemic developmental anomalies are apparently related by virture of a common neural crest origin. The development of the anterior segment is extremely complex and is dependent upon the presence or absence of certain local factors (including extracellular matrices and glycoproteins), inductors, receptors, and specific time sequencing. Understanding anterior segment anomalies and their systemic associations requires an understanding of neural crest proliferation and migration patterns; and they may be unified under the designation of neurocristopathies. Goldenhar's syndrome, not previously considered a neurocristopathy, may be considered one on the basis of the relationship between clinical findings and neural crest embryology.

Abnormalities, Multiple↗

The autoimmune diabetes locus Idd9 regulates development of type 1 diabetes by affecting the homing of islet-specific T cells.

Several genetic insulin-dependent diabetes (Idd) intervals that confer resistance to autoimmune diabetes have been identified in mice and humans, but the mechanisms by which they protect against development of diabetes have not been elucidated. To determine the effect of Idd9 on the function of islet-specific T cells, we established novel BDC-Idd9 mice that harbor BDC2.5 TCR transgenic T cells containing the Idd9 of diabetes-resistant B10 mice. We show that the development and functional responses of islet-specific T cells from BDC-Idd9 mice are not defective compared with those from BDC mice, which contain the Idd9 of diabetes-susceptible NOD mice. Upon transfer, BDC T cells rapidly induced severe insulitis and diabetes in NOD.scid mice, whereas those from BDC-Idd9 mice mediated a milder insulitis and induced diabetes with a significantly delayed onset. BDC and BDC-Idd9 T cells expanded comparably in recipient mice. However, BDC-Idd9 T cells accumulated in splenic periarteriolar lymphatic sheaths, whereas BDC T cells were mainly found in pancreatic lymph nodes and pancreata of recipients, indicating that the transferred T cells differed in their homing. We provide evidence that the migration pattern of transferred BDC and BDC-Idd9 T cells at least partly depends on their differential chemotaxis toward the CCR7 ligand CCL19. Taken together, our data show that the Idd9 locus regulates development of type 1 diabetes by affecting the homing of islet-specific T cells.

Animals↗

Visceral leishmaniasis unresponsive to pentostam caused by Leishmania tropica in Kenya.

We report the characterization of 6 Leishmania tropica isolates from 2 patients with visceral leishmaniasis who were unresponsive to treatment with sodium stibogluconate. The Leishmania isolates, MHOM/KE/81/NLB-029A, -029XIB, and -029XIC and MHOM/KE/81/NLB-030I, -030B, and -030XXA, all from splenic aspirates, were characterized by cellulose acetate electrophoresis using 11 enzymes: malate dehydrogenase, malic enzyme, phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, superoxide dismutase, glutamate-oxaloacetate transaminase, adenylate kinase, nucleoside hydrolase, mannose phosphate isomerase, glucose phosphate isomerase, and phosphoglucomutase. Isozyme migration patterns were indistinguishable from those of 2 WHO reference strains of Leishmania tropica (MHOM/SU/60/LRC-L39, NLB-305 and MHOM/IQ/OO/LRC-L36, NLB-067). These are the first reported cases of visceral leishmaniasis (kala-azar) caused by L. tropica in Africa; these cases were refractory to sodium stibogluconate.

Animals↗