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Impact of control measures on malaria transmission and general mortality.

This paper is an attempt to relate modifications observed in general and infant mortality rates with the dynamic changes in transmission induced by malaria control measures. The observations indicated relationships between the efficacy of control and a decrease in mortality. The daily parasitological inoculation rate was reduced from 0.00958 infective bites per individual before treatment to 0.00037 after treatment (a decrease of 96%). In two years, general mortality decreased from 23.9 to 13.5 deaths per 1000 population and infant mortality decreased from 157 to 93 per 1000 live births. This indirect benefit of malaria control deserves attention in a wider assessment of measures directed against vector-borne diseases.

Adult↗

[Changes in the hemoglobin A2 level of patients with ischemic heart disease].

40 patients with ischemic heart disease were studied. In 60% of them a higher content of HbA2 was found. These data for higher frequency of HbA2 among the patients with ischemic heart disease do not correspond with the average incidence of the genetically determined anomaly A2-beta-thalassemia among the Bulgarian population. The negative data for increased methemoglobin, the shift of the oxygen dissociation curve to the right toward increased oxygen release from the hemoglobin molecule, the normalization of HbA2 after several days, the lack of anomalous fraction in the analyses lead to the conclusion that HbA2 plays a compensatory role in patients with ischemic heart disease and its dynamic changes could be used as a diagnostic test for ischemia.

Adult↗

Practical design criteria for a dynamic ratio imaging system.

Problems encountered and solutions devised during the construction of a productive Ca2(+)-imaging system are discussed. Many of these relate to the rapid and interactive nature of experiments on cytosolic Ca2+. The emphasis on accurate photometric quantitation of dynamically changing images contrasts with that of most image-processing software packages, which concentrate either on leisurely massage of static images or on descriptions of lateral motions of objects without concern for their brightnesses. Particularly important goals for Ca2(+)-imaging include real-time ratioing, psychophysically effective display formats, ease of experiment annotation, mass storage of image sequences, automated extraction of time courses and population statistics, aids to presenting images for seminars and publications, and program modifiability.

Calcium↗

Simulation of dynamic changes of human T-cell leukemia virus type I carriage rates.

The human T-cell leukemia virus type I (HTLV-I) is transmitted via breast milk, semen, or blood transfusion. The last route was not responsible for HTLV-I infection before the advent of modern medicine, nor will it be a major route in the future because anti HTLV-I antibody-positive blood is now screened out. Thus, the carriage rates in various areas of Japan have to be explained by the former two transmission methods. Based on the relationship between the two modes of transmission and carriage rates, several simulation experiments were performed. These experiments revealed that: (a) No population with a vertical transmission rate lower than 50% can be maintained as endemic for the virus. (b) Slight differences in horizontal transmission rates can cause a large change of the carriage rates. (c) A 1,000-fold carriage rate difference would become indistinguishable within a hundred generations if both modes of transmission were operating at nearly the same rate. (d) The probability of a formerly non-endemic population becoming endemic due to a single female carrier is not negligible. (e) Prevention of vertical transmission is much more effective in lessening the carriage rate within a short period of time than is prevention of horizontal transmission. A simulation for a real population is also presented.

Age Factors↗

Oncogene expressions detected by in situ hybridization of squamous metaplasia, dysplasia and primary lung cancer in human.

In order to elucidate the dynamic changes of oncogene expression in the sequential cascade of squamous metaplasia, dysplasia, and squamous cell carcinoma of the bronchial epithelium, hybridization in situ was employed with a biotinylated oncogene probe. The expression of c-myc was localized exclusively in nuclei. While normal bronchial epithelium revealed no discernible clumps of c-myc grains, except occasional grains less than 3 per cell, squamous metaplasia showed increased number of grains and a few clusters of c-myc grains. In dysplasia, c-myc expression was more intensive than in squamous metaplasia. Approximately, 1/3 to 2/3 of tumor cell populations of squamous cell carcinomas of the lung revealed tremendously increased c-myc expression. In addition clumpy grains of c-myc in squamous cell carcinoma appeared more frequently than in squamous metaplasia or dysplasia. The c-myc expression was found to vary between different samples and within each cancer, and not all cancer cells expressed c-myc. These data indicate that c-myc oncogene plays it's role on reprogramming for growth control of cell populations particularly in multistage carcinogenesis and progression of lung cancer. These dynamic alterations of c-myc expression suggest that neoplastic transformation may occur conceivably at the dysplastic phase eventually resulting in carcinoma in situ. This means, in turn, squamous dysplasia is a putative precancerous lesion of the human lung.

Bronchial Neoplasms↗

Langerhans cells in human allergic contact dermatitis contain varying numbers of Birbeck granules. Double staining immunohistochemistry with OKT6 and Lag antibody.

Dynamic changes in human Langerhans cells (LCs) were studied with OKT6, anti-HLA-DR antibody, and Lag antibody in allergic contact dermatitis (ACD). Both T6-positive (T6+) cells and Lag-positive (Lag+) cells in the epidermis decreased in number from 0 to 48 h, but then gradually increased after day 7 of ACD. Lag+ cells after day 7 manifested a variety of staining intensities from weak to strong. It was also shown, after day 7, that some T6+ cells were Lag negative whereas all Lag+ cells were T6 positive. Flow cytometric analysis suggested that Lag-strongly-positive cells and Lag-weakly-positive cells belonged to the same population, and that the relative amount of Lag antigens in T6+ LCs gradually increased after day 7. Immunoelectron microscopy revealed that the Lag-strongly-positive cells contained numerous Lag-reactive Birbeck granules (BGs) whereas the Lag-weakly-positive cells contained fewer BGs in the cytoplasm. In some Lag-weakly-positive cells, no BGs were detected.

Adult↗

Dynamic changes in the density of radial glial fibers of the developing murine cerebral wall: a quantitative immunohistological analysis.

The density of radial glial fibers in the developing murine cerebral wall decreases dramatically during the terminal week of gestation. The present analysis characterizes these variations of fiber density quantitatively. Radial glial fibers were stained with monoclonal antibody RC2. Fibers were counted in a standard area of 2,000 microns2, passing orthogonally to the fiber long axis. At E14, fiber density is maximum and relatively uniform throughout the full width of the cerebral wall. Subsequently, the overall glial fiber density decreases and fiber density gradients emerge in the transmural span of fibers. These radial fiber density gradients are marked by sharp declines at the level of the ventricular-subventricular zone and in the zone of transition between intermediate zone (IZ) and cortical plate. In the interval E14-P0, the decrease in densities of fibers crossing the IZ is commensurate with the predicted diluting effects of tissue expansion with growth. By contrast, the decrease in fiber densities in ascent across the cortical plate beyond E14 through E17 exceeds that predicted by growth. The observations suggest that a substantial population of radial glial fibers do not span the full ventricular zone to the cerebral surface. A major contingent appears to extend only as far as the external sagittal stratum/subplate through E16. Subsequently, at a time when supragranular cortical layers are being assembled, the full set of fibers appears to extend more uniformly through the cortical strata. The late surge of fibers would be appropriate to the intercalation of groupings of neurons of the supragranular layers.

Animals↗

[Astrocytic proliferation in the brain adjacent to infarcted lesion: immunohistochemical study of astroprotein (GFAP) and bromodeoxyuridine (BrdU)].

Although cerebral infarction is a destructive process of nerve cells and brain tissue, the nature is not exclusively disintegrating but also includes active cellular reaction which may modify the progression of tissue damage. Most prominent cellular reaction in the area surrounding infarction can be recognized as a trophic or proliferative change of glial cells. In the present study we produced a focal cerebral ischemia in Mongolian gerbils and investigated the dynamic change of astrocytes in the brain adjacent to thalamic infarction. Using immunohistochemical methods, astrocytes were identified with the antibody to astroprotein (GFAP) and the DNA synthesizing (S phase) cells were detected with the antibody to bromodeoxyuridine (BrdU). The posterior communicating artery of a gerbil was occluded by coagulation through the trans-tympanic bulla approach under general anesthesia with ketamine hydrochloride (80 mg/kg, i.p.). Thirty min after intravenous administration of BrdU (200 mg/kg), animals were sacrificed by transcardiac perfusion with 75% ethanol on days 1, 2, 3, 5 and 7 post-infarction. Ethanol-fixed, paraffin-embedded blocks were cut coronally into 6 microns-thick sections at the level of dorsal hippocampus. Double-labeled immunohistochemical technique (avidin biotin peroxidase-complex method) was carried out with each antibody using 3,3'-diaminobenzidine tetrahydrochloride and 4-chloro-1-naphthol as chromogens. The population of GFAP-positive cells and their S-phase fraction (the number of BrdU-positive nuclei divided by the number of GFAP-positive cells expressed in per cent, %) were examined. The data demonstrated that the regional GFAP-positive cells increased continuously between days 1 to 5 (105.9 to 528.8 cells/mm2) postinfarction (44.6 cells/mm2 in normal brain).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Dynamic changes in the epidemiological patterns of measles in the People's Republic of Bulgaria after mass vaccination and revaccination].

The main epidemiological regularities of measles before vaccination (1960--1968) and at the stage of mass vaccination (1969--1977) were studied. The average annual incidence of measles has been reduced from 423.97 to 279.72 per 100,000, mortality from 0.56 to 0.10 0/0000, and lethality from 0.13% to 0.04%. The dynamical changes of postvaccination immunity were uneven: in 1969 vaccinations covered 30.67%, in 1970 28.82%, in 1971 64.09%, in 1972 53.38%, in 1973 59.61%, in 1974 67.53%, and in 1975 69.04%. The level of herd immunity in those years was lower than the optimal (45.35%, 43.97%, 67.71%, 68.13%, 74.65%, 83.25%, and 84.63%, respectively). In the first part of 1976 a general immunoprophylactic campaign was carried out including vaccination of the unvaccinated children born in 1963--1975 and revaccination of all those vaccinated one year before the campaign. Primary vaccination increased the coverage by 11.25%, and revaccination increased the portion of seropositive subjects by 5.2%. As a result, a sufficiently high level of general herd immunity has been achieved (1976--96.02%, 1977--96.10%) and the incidence decreased accordingly (1976--192.69 0/0000, 1977--9.17 0/0000).

Bulgaria↗

Changes in expression of Ia, Thy-1, and Ly-5 antigens in epidermal cells during delayed contact sensitivity reactions in mice: flow cytometric analysis.

Ia antigen-bearing (Ia+) Langerhans cells have attained an important position as immunocompetent cells in the epidermis. Recently there have been successive reports on other new possible candidates for immunocompetent cells in the epidermis, i.e., Ia+ keratinocytes and dendritic Thy-1 antigen-bearing (Thy-1+) epidermal cells which also express Ly-5 antigen and asialo-GM1. Based on our previous findings that in allergic contact sensitivity reactions, keratinocytes express Ia antigen 3-9 days postchallenge, in this report, we have attempted to define more clearly the dynamic changes of Ia+ keratinocytes and dendritic Thy-1+ epidermal cells by enumeration of the precise percentages of Ia+, Thy-1+, and Ly-5 antigen-bearing (Ly-5+) cells in epidermal cells at various times of the challenge phase in allergic contact sensitivity reactions by use of a fluorescence-activated cell sorter. By 24 h postchallenge, the percentages of Ia+, Thy-1+, and Ly-5+ cells showed hardly any change. There were approximately 2% Ia+ cells, 50% Thy-1+ cells which consist of 2 populations (i.e., 45% weakly Thy-1 antigen-positive cells and 4% strongly Thy-1 antigen-positive cells), and 3.5% Ly-5+ cells. From 48 h postchallenge, however, the percentage of Ia+ cells and that of Thy-1+ cells began to increase and reached a plateau, with approximately 20% Ia+ cells and 70% Thy-1+ cells, respectively, at 120 h postchallenge. The change of the percentages of Ly-5+ cells appears to correspond to that of strongly Thy-1 antigen-positive cells. Only at 48 h postchallenge, Ly-5+ cells and strongly Thy-1 antigen-positive cells showed a small increase in number, comprising approximately 10% of the epidermal cells. These data suggest that among Thy-1+ epidermal cells, strongly Thy-1 antigen-positive cells correspond to dendritic Thy-1+ epidermal cells, and in contact sensitivity reactions in mice, dendritic Thy-1+ epidermal cells show only a minor dynamic change in contrast to Ia+ cells, in which more than 15% of keratinocytes express Ia antigen from 48 h postchallenge.

Animals↗

Quantitative analysis of mating behavior in aging male Drosophila melanogaster.

Dynamic changes in quantitative aspects of mating behavior of the male fruit fly as its life unfolds, from eclosion through maturity (peak performance) and "physiological death" (loss of fertility followed by complete loss of ability to mate), towards actual death, have been identified in this work by observations and measurements on 28 male fruit flies of the Oregon R strain studied individually. At weekly sessions from the first day of their imaginal life until their natural death, each fly was given the opportunity to mate with up to three virgin females during a one-hour period. Length of the latency period of each accomplished mating and duration of copulation were recorded. After mating the females were allowed to lay eggs for 24 hours and the number of offspring was counted 26 days later. The period between 1 and 4 weeks of age is characterized by peak and fairly constant performance: multiple matings, short latencies, long durations of copulation, and high degree of fertility (number of offspring); then a decline sets in, in some measures slower than in others, as the flies age. Large intra- and inter-individual variabilities were, however, found which obscure possible correlations between individual measures of mating ability and length of life. At the individual level, a preliminary analysis showed a good correlation (r = 0.80 and 0.79) between life span and week of last mating (onset of impotence) or week of last fertile mating (onset of sterility). At the population level it was found that a number of measures, i.e. number of remaining maters at each age, number of remaining fertile maters and total number of matings, had an age-course similar to survivorship but anticipated it by 4--6 weeks. Other measures, such as number of multiple matings and number of offspring declined with age faster than survivorship.

Aging↗

Serum gonadotropins and gonadal steroids associated with ovulation and egg production in sea turtles.

Changes in serum concentrations of gonadotropins and gonadal steroids during the periovulatory period were monitored in green, Chelonia mydas, and loggerhead, Caretta caretta, sea turtles. Turtles were from natural populations that nest on a coral island on the Great Barrier Reef. After nesting, each turtle was transferred to a holding tank and held for a maximum of 8 days. A time series of blood samples was obtained from each of five sea turtles (three C. mydas and two C. caretta) starting immediately after nesting and then at approximately 12-hr intervals until the time of release. Prior to release back into the ocean, each turtle was examined by laparoscopy to verify that ovulation had occurred. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (PRO), and testosterone (T) in both species exhibited significant changes during this period. Surges of FSH, LH, and PRO were evident within approximately 20 to 50 hr after each turtle had nested. The significant change in FSH concentration during the periovulatory period is the first such report for a reptile. Coincident with maximal concentrations of FSH, LH, and PRO was a decline in T concentrations in both species. Estradiol-17 beta concentrations were near or below assay sensitivity in the C. mydas, whereas those in the C. caretta were detectable but exhibited no significant changes. The dynamic changes in FSH, LH, PRO, and T concentrations are consistent with the hypothesis that these hormones facilitate specific physiological events during ovulation and egg production.

Animals↗

Age-related changes in naive and memory CD4+ T cells in healthy human children.

Subsets of CD4+ T cells originally identified functionally as suppressor-inducer and helper-inducer populations have recently been reinterpreted as naive and memory maturational states. The subsets can be identified by the surface expression of CD45R and CDw29, respectively. Using two-color flow cytometric analysis, we measured these CD4+ T cell subsets in two samples of cord blood and in 26 healthy children between the ages of 1 and 19 years. As has been reported by others, we observed that the majority of CD4+ T cells in cord blood consist predominantly of the CD45R+ subset. With aging we could demonstrate a gradual acquisition of CDw29+, CD4+ T cells and a concomitant gradual decrease in the percentage of CD45R+, CD4+ T cells. These age-related changes are consistent with the concept of naive (CD45R+) and memory (CDw29+) subsets. Further, because of the dynamic changes, their utilization as prognostic indicators in immunologic disease states cannot be applied to children in the same manner as adults.

Adolescent↗

Influence of development and aging on nicotinic receptor subtypes in rodent brain.

The influence of development and aging on nicotinic receptor subtypes in rodent brain was investigated. 3H-nicotine and 3H-acetylcholine (3H-ACh) were used as receptor ligands. Specific binding sites for 3H-nicotine and 3H-ACh were detected in mouse brain during the late prenatal period. A drop in the number of 3H-nicotine and 3H-ACh binding sites was measured shortly after birth. The 3H-nicotine and 3H-ACh binding sites showed different time courses during prenatal development. Competition experiments using unlabelled (-)nicotine and 3H-nicotine revealed one population of high affinity nicotinic binding sites in the cortex of 1-day and 5-day-old mice whereas both a set of high and low affinity binding sites were found in adult mice. The proportion of cortical high and low affinity nicotinic binding sites did not change with aging although the absolute amount of high affinity nicotinic binding sites decreased. The 3H-nicotine binding showed different temperature dependence in rat brain of different ages. The results illustrate dynamic changes in nicotinic receptor properties during life span of rodents.

Aging↗

Proteomic analysis reveals early pathological defects in corticospinal motor neurons of a spastin model of hereditary spastic paraplegia, which are improved by NU-9 treatment.

Upper motor neuron (UMN) degeneration is a characteristic feature of hereditary spastic paraplegia (HSP), a genetically heterogeneous heritable neurodegenerative disorder resulting from mutations in over ninety genes. The mutations in the SPAST gene, which encodes the microtubule-severing protein spastin, are responsible for about 40% of all HSP cases. To date, the cellular and molecular mechanisms linking mutant spastin protein to UMN vulnerability in HSP patients remain unknown and there are no disease modifying therapies. To address this knowledge gap, we isolated pure populations of corticospinal motor neurons (CSMN; a.k.a. UMN in mice) from SPASTC448Y-UeGFP reporter mice at two pre-symptomatic time points and performed bottom-up proteomic analyses to reveal changes in their proteome that informs the underlying causes of their initial vulnerability. We find dynamic changes in their proteome and that limitations with cytoarchitectural integrity and stability of key organelles contribute to their neuronal vulnerability. Since the compound NU-9 was shown to improve similar cellular problems in CSMN that are diseased due to misfolded SOD1 toxicity and TDP-43 pathology, we further investigated its effect on the well-established pathological features of HSP that are recapitulated in the SPASTC448Y mice. We find that NU-9 treatment (100 mg/kg, for 100 days) significantly prevented degeneration of corticospinal axons, restored the integrity of mitochondria and endoplasmic reticulum, and reduced the presence of electron-dense accumulations in the CSMN of SPASTC448Y mice.

Animals↗

Dynamic changes in chromosome and nuclear architecture during maturation of normal and ALS C9orf72 motor neurons.

We have investigated changes in chromosome conformation, nuclear organization, and transcription during differentiation and maturation of control and mutant motor neurons harboring hexanucleotide expansions in the C9orf72 gene that cause amyotrophic lateral sclerosis (ALS). Using an in vitro reprogramming, differentiation and neural maturation protocol, we obtained highly purified populations of post-mitotic motor neurons for both normal and diseased cells. As expected, as fibroblasts are reprogrammed into iPSCs, and as iPSCs differentiate into motor neurons, chromatin accessibility, chromosome conformation, and nuclear organization change along with large-scale alterations in transcriptional profiles. We find that the transcriptome changes extensively during the first three weeks of post-mitotic neuronal maturation, with thousands of genes changing expression, but then is relatively stable for the next three weeks. In contrast, chromosome conformation and nuclear organization continue to change over the entire 6-week maturation period: chromosome territoriality increases, long-range interactions along chromosomes decrease, compartmentalization strength increases, and centromeres and telomeres increasingly cluster. In motor neurons derived from ALS patients such changes in chromosome conformation were much reduced. Chromatin accessibility changes also showed delayed maturation. The transcriptome in these cells matured relatively normally but with notable changes in expression of genes involved in lipid, sterol and mitochondrial function. We conclude that neural maturation is associated with large scale post-mitotic changes in gene expression, chromosome conformation and nuclear organization, and that these processes are defective in motor neurons derived from ALS patients carrying C9orf72 hexanucleotide repeat expansions.

Journal Article↗

Role of the health professional in ending the tobacco pandemic: clinic, classroom, and community.

Physicians and other health professionals have become complacent about the tobacco pandemic, because there is a mistaken belief that the war on smoking has been won. In reality, the survival from lung cancer is little better than it was 30 years ago, and cigarettes have become the most advertised and promoted product in society. The prevalence of overall smoking in the United States has declined by only 0.5%/y during the past decade. Among certain US minority populations, the decline has been far less or nonexistent. Traditional efforts to control the tobacco pandemic have been reactive and static, whereby government agencies, schools, and health professionals provide the public with generic information about the adverse health effects of smoking. As a result of these efforts, it is assumed that individuals will act to change their behavior. In contrast, the tobacco industry is proactive and dynamic, changing its brand-name strategies through advertising and promotion. To more effectively combat tobacco use, health officials need to move beyond patient education and adopt a more active model that includes clinic-based, school-based, and community-based tobacco-control strategies. Use of humorous, satirical images as part of paid counteradvertising campaigns and proactive health education curricula should be part of a concerted effort to end the tobacco pandemic and limit the promotional influence of tobacco companies.

Consumer Advocacy↗

[Various results of the study of medico-biological aspects of alcoholism in Siberia and Far East].

To study the dynamic changes in alcohol abuse, a new methodological approach has been developed which implies staged realization. Stage one was aimed at the search for integral clinical-dynamic characteristics as well as social and psychological properties to make identification of the clinical phenotype reliable. Stage II--at introduction of integral constitution-morphology indicators representative of the disease predisposition-stability. The analysis of medicosocial characteristics for the last 8 years has been performed at Stage III. Calcium homeostasis and related hormones and enzymes were evaluated at Stage IV. The data obtained permitted identification of a complex of structural manifestations underlying alcohol embryopathy of the brain.

Alcoholism↗