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Biomedical subjects

M Manuel

Publications and source records attributed to M Manuel.

At least 19 recordsLinked to original sources
PubMed2000

Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis.

IL-17 is a novel, CD4+ T cell-restricted cytokine. In vivo, it stimulates hematopoiesis and causes neutrophilia consisting of mature granulocytes. In this study, we show that IL-17-mediated granulopoiesis requires G-CSF release and the presence or induction of the transmembrane form of stem cell factor (SCF) for optimal granulopoiesis. However, IL-17 also protects mice from G-CSF neutralization-induced neutropenia. G-CSF neutralization completely reversed IL-17-induced BM progenitor expansion, whereas splenic CFU-GM/CFU-granulocyte-erythrocyte-megakaryocyte-monocyte was only reduced by 50% in both Sl/Sld and littermate control mice. Thus, there remained a significant SCF/G-CSF-independent effect of IL-17 on splenic granulopoiesis, resulting in a preservation of mature circulating granulocytes. IL-17 is a cytokine that potentially interconnects lymphocytic and myeloid host defense and may have potential for therapeutic development.

3T3 Cells↗
PubMed2000

Cyclosporin A induces an atypical heat shock response.

Cyclosporin A is a widely used immunosuppressive drug having toxic side effects, in particular on kidneys and liver, as a result of its action on different molecular targets. Here we demonstrate that low doses of CsA are able to induce the expression of the heat shock protein HSP27 and its hyperphosphorylation. It also activates the two heat shock transcription factors, HSF1 and HSF2. Since these factors have been shown to be activated by proteasome inhibition, we tested the hypothesis that the inhibitory action of CsA on the proteasome might be responsible for the activation of HSFs and the subsequent expression of HSP27. The increase in multiubiquitinated proteins as well as the stabilization of p53 following CsA addition argues in favor of this hypothesis. The kidney BSC-1 cells are highly responsive to the addition of CsA: the possible link between HSP27 induction and hyperphosphorylation and nephrotoxicity is discussed.

Animals↗
PubMed2000

Homeobox gene diversification in the calcareous sponge, Sycon raphanus.

Knowledge of the developmental mechanisms in living basal metazoan phyla is crucial for understanding the genetic bases of morphological evolution in early animal history. We looked for homeobox genes in the calcareous sponge, Sycon raphanus, using the polymerase chain reaction. Partial sequences of eight homeoboxes were recovered, five of which are assignable to the NK-2 class of homeoboxes. The three remaining sequences are related members of a new class of homeoboxes, the Sycox class, showing limited similarity to bilaterian Lbx, Hlx, HEX, En, and Cad classes. Among the five NK-2 class homeoboxes are four closely related sequences occupying a divergent position within the class, the remaining one on the contrary showing high sequence similarity with members of the NK-2 family, a particular subgroup within the NK-2 class, previously known only from the Bilateria. This suggests that diversification of the NK-2 class occurred early in metazoan history. Altogether, the results reveal an unexpected diversification of homeobox genes in S. raphanus.

Amino Acid Sequence↗
PubMed2000

The comparison of beta-thymosin homologues among metazoa supports an arthropod-nematode clade.

The definition of an Ecdysozoa clade among the protostomians, including all phyla with a regularly molted alpha-chitin-rich cuticle, has been one of the most provocative hypotheses to arise from recent investigations on animal phylogeny. Here we present evidence in favor of an arthropod-nematode clade, from the comparison of beta-thymosin homologues among the Metazoa. Arthropods and nematodes share the absence of the highly conserved beta-thymosin form found in all other documented bilaterian phyla as well as sponges, and the possession of a very unusual, internally triplicated homologue of the beta-thymosin protein, unknown in other phyla. We argue that such discrete molecular character is phylogenetically very powerful and provides strong evidence for the monophyly of an arthropod-nematode clade.

Amino Acid Sequence↗
PubMed1999

Genomic structure and chromosomal localization of the mouse Hsf2 gene and promoter sequences.

The mouse heat shock factor 2 (HSF2) cDNA was previously cloned by homology to HSF1, the heat shock factor involved in the cellular response to stress [Sarge, K.D., Zimarino, V., Holm, K., Wu, C., Morimoto, R.I., Cloning and characterization of two mouse heat shock factors with distinct inducible and constitutive DNA-binding ability. Genes Dev. 5 (1991) 1902-1911]. HSF2 is active in restricted cell types during pre- and post-implantation stages of development, and only in male germ cells of adult mice. However, the function of this factor remains elusive. We report here the cloning of the mouse Hsf2 gene and its genomic structure. We show that the gene is composed of 13 exons of variable sizes spanning at least 43kb in the genome. The transcription start site has been determined, and upstream sequences with promoter activity have been identified by their ability to direct the expression of a luciferase reporter gene in transfected cells. A preliminary analysis of the proximal promoter sequence determined that the TATA box is absent, but that a GC-rich region with several potential binding sites for transcription factors is present. The gene has been mapped to mouse chromosome 10 by in-situ hybridization on metaphase chromosomes.

Animals↗
PubMed1999

Horizontal transfer of genetic material among Saccharomyces yeasts.

The genus Saccharomyces consists of several species divided into the sensu stricto and the sensu lato groups. The genomes of these species differ in the number and organization of nuclear chromosomes and in the size and organization of mitochondrial DNA (mtDNA). In the present experiments we examined whether these yeasts can exchange DNA and thereby create novel combinations of genetic material. Several putative haploid, heterothallic yeast strains were isolated from different Saccharomyces species. All of these strains secreted an a- or alpha-like pheromone recognized by S. cerevisiae tester strains. When interspecific crosses were performed by mass mating between these strains, hybrid zygotes were often detected. In general, the less related the two parental species were, the fewer hybrids they gave. For some crosses, viable hybrids could be obtained by selection on minimal medium and their nuclear chromosomes and mtDNA were examined. Often the frequency of viable hybrids was very low. Sometimes putative hybrids could not be propagated at all. In the case of sensu stricto yeasts, stable viable hybrids were obtained. These contained both parental sets of chromosomes but mtDNA from only one parent. In the case of sensu lato hybrids, during genetic stabilization one set of the parental chromosomes was partially or completely lost and the stable mtDNA originated from the same parent as the majority of the nuclear chromosomes. Apparently, the interspecific hybrid genome was genetically more or less stable when the genetic material originated from phylogenetically relatively closely related parents; both sets of nuclear genetic material could be transmitted and preserved in the progeny. In the case of more distantly related parents, only one parental set, and perhaps some fragments of the other one, could be found in genetically stabilized hybrid lines. The results obtained indicate that Saccharomyces yeasts have a potential to exchange genetic material. If Saccharomyces isolates could mate freely in nature, horizontal transfer of genetic material could have occurred during the evolution of modern yeast species.

Cell Nucleus↗
PubMed1998

Contribution of reactive oxygen and nitrogen species to particulate-induced lung injury.

Recently, a second pathway for the generation of potential oxidants with the reactivity of the hydroxyl radical without the need for metal catalysis has been described. In response to various inflammatory stimuli, lung endothelial, alveolar, and airway epithelial cells, as well as activated alveolar macrophages, produce both nitric oxide (.NO) and superoxide anion radicals (O2.-). .NO regulates pulmonary vascular and airway tone and plays an important role in lung host defense against various bacteria. However, .NO may be cytotoxic by inhibiting critical enzymes such as mitochondrial aconitase and ribonucleotide reductase, by S-nitrosolation of thiol groups, or by binding to their iron-sulfur centers. In addition, .NO reacts with O2.- at a near diffusion-limited rate to form the strong oxidant peroxynitrite (ONOO-), which can nitrate and oxidize key amino acids in various lung proteins such as surfactant protein A, and inhibit their functions. The presence of ONOO- in the lungs of patients with acute respiratory distress syndrome has been demonstrated by measuring levels of nitrotyrosine, the stable product of tyrosine nitration. Various studies have shown that inhalation or intratracheal instillation of various respirable mineral dusts or asbestos fibers increased levels of inducible nitric oxide synthase mRNA. In this presentation, we review the evidence for the upregulation of .NO in the lungs of animals exposed to mineral particulates and assess the contribution of reactive nitrogen species in the pathogenesis of the resultant lung injury.

Animals↗
PubMed1998

Behavior of infants with iron-deficiency anemia.

This study tested the hypothesis that infants with iron-deficiency anemia show behaviors, such as increased proximity to caregivers, increased wariness or hesitance, and decreased activity, that could contribute to "functional isolation." The behavior of 52 Costa Rican 12- to 23-month-old infants with iron-deficiency anemia was contrasted with that of 139 comparison group infants with better iron status during free play and mental and motor testing and in the home. Infants with iron-deficiency anemia maintained closer contact with caregivers; showed less pleasure and delight; were more wary, hesitant, and easily tired; made fewer attempts at test items; were less attentive to instructions and demonstrations; and were less playful. Adult behavior also differed. The results indicate that iron-deficiency anemia in infancy is associated with alterations in affect and activity, suggesting that functional isolation is a useful framework for understanding poorer developmental outcome in iron-deficiency anemia, the world's most common single nutrient deficiency.

Affect↗
PubMed1994

Abundance and prevalence of Culicoides (Diptera: Ceratopogonidae) on some Philippine chicken farms.

In total, 10,067 biting midges of the genus Culicoides comprising 17 species were collected in a light trap survey of 50 chicken farms in the province of Batangas, southern Luzon, Philippines, between 14 September and 5 December 1988. The species of greatest prevalence and abundance were Culicoides effusus Delfinado, Culicoides peregrinus Kieffer, and Culicoides palpifer Sen & Das Gupta. Engorged females of C. effusus, C. peregrinus, C. palpifer, Culicoides oxystoma Kieffer, Culicoides arakawae (Arakawa), Culicoides guttifer (Meijere), Culicoides albibasis Wirth & Hubert, Culicoides huffi Causey, Culicoides clavipalpis Mukerji, and Culicoides wenzeli Delfinado were collected. The abundance and prevalence of C. effusus, C. peregrinus, and C. C. palpifer in the overall sample of farms as well as in farms with previous occurrence of leucocytozoonosis indicated that these species are potential vectors of Culicoides-borne Leucocytozoon caulleryi Mathis & Leger among chickens in this area. Although blood-engorged females of C. arakawae were collected frequently, the prevalence and abundance of this species were limited.

Animals↗
PubMed1989

Randomized clinical trial with intrauterine devices (levonorgestrel intrauterine device (LNG), CuT 380Ag, CuT 220C and CuT 200B). A 36-month study. Indian Council of Medical Research Task Force on IUD.

A total of 1905 subjects were randomly allocated to four types of intrauterine devices (IUDs) and were observed for 45,683 woman-months of use. While no method failure was observed with levonorgestrel (LNG) IUD, 11 women became pregnant with other devices; 4 with Copper T 380Ag, 1 with Copper T 220C, and 6 while using Copper T 200B, indicating method failure rates of 1.0, 0.3 and 1.6, respectively, at 36 months of use. These rates were within acceptable range. Continuation rates were significantly lower with LNG IUD (74.5, 58.7, 38.8 at 1 year, 2 years and 3 years, respectively) as compared to other copper devices, which ranged between 82.4 to 84.4 at 1 year, 66.6 to 69.9 at 2 years and 45.4 to 50.4 at 3 years. The difference in continuation rates was mainly due to menstrual disturbances (e.g. amenorrhoea, irregular bleeding) which were higher with LNG IUD (27.9 per 100 users) as compared to the copper devices (13.4-15.4 per 100 users) at 36 months of use. The risk of expulsion ranged between 8.3 to 10.6 per 100 users and was comparable for all the devices. The observations from the present study based on 36 months of experience with different intrauterine devices do not indicate the need to replace CuT 200, the device currently in use in the National Programme.

Adolescent↗
PubMed1985

Indian Council of Medical Research. Task Force on Hormonal Contraception: Phase II randomized clinical trial with norethisterone oenanthate 50 mg alone and in combination with 5 mg or 2.5 mg of either estradiol valerate or cypionate as a monthly injectable contraceptive.

A Phase II multicentric study was carried out to compare the different contraceptive treatment schedules of the monthly injectable consisting of norethisterone oenanthate (NET OEN) 50 mg either given alone or in combination with estrogen esters, 2.5 or 5 mg of estradiol valerate (E2 Val.) or estradiol cypionate (E2 Cyp.). A total of 364 women were observed for 1686 months of use. Analysis of the bleeding pattern data indicated that NET OEN 50 mg when given alone gave rise to delayed cycles and/or amenorrhoea. However, the addition of estrogen esters in a dose of either 2.5 or 5 mg provided significantly better bleeding patterns. Of the different treatment schedules investigated, the combination of NET OEN 50 mg with E2 Val. 5 mg provided more consistent and better cycle control. These findings however need further validation on a larger study sample.

Adult↗
PubMed1979

Computer analysis of etiology and pregnancy rate in 636 cases of primary infertility.

Since the rate of pregnancy is a function of time, conventional pregnancy rates (number of patients achieving pregnancy per number of patients treated) are inadequate for counseling unless the follow-up period is specified. To overcome this problem, the expectancy of pregnancy for 636 cases of primary infertility was calculated with the assumption that the patients were followed up indefinitely. The overall "conventional" pregnancy rate was 38%, whereas the overall expectancy of pregnancy was 64%. Endometriosis was found to be the most common factor, comprising 25% of the cases, with a pregnancy rate of 31% and an expectancy of 52%. The expectancy of future pregnancy in a patient who has not achieved pregnancy by a given time is presented for each etiologic factor. This paper also presents a comparison of expectancies of pregnancy by different treatments, which may be helpful in selecting appropriate therapy.

Adult↗
PubMed1976

The age of occurrence of gonadal tumors in intersex patients with a Y chromosome.

A total of 320 intersex patients with a Y chromosome were classified into four groups; (1) gonadal dysgenesis, (2) asymmetrical gonadal differentiation, (3) virilizing male hermaphroditism and (4) feminizing male hermaphroditism (testicular feminization syndrome). Of these 320 cases, 98 were from the files of The Johns Hopkins Hospital and the remainder from the literature. The incidence of tumors in relation to age and clinical classification was analyzed by computer. The results were plotted for each group. It was found that the percentage of tumors rose appreciably soon after the age of puberty in the first three groups, and it was concluded that the gonads were best removed before the age of puberty. In the case of testicular feminization patients, procrastination until the age of 25 could be considered, if one were willing to assume the risk of neoplasia of about 3.6 per cent until then.

Adolescent↗
PubMed1976

Methyltestosterone treatment of infertility associated with pelvic endometriosis.

Sixty-four patients who had infertility associated only with endometriosis were treated with methyltestosterone, 5 mg/day, continuously for a period of 6 months. The patients continued to ovulate while receiving medication and 12 patients became pregnant, on an average, 6 months after the initiation of therapy. A computer analysis indicated that approximately 30% of the patients could expect pregnancy within 2 years after the testosterone treatment was begun. The side effects of the low-dose methyltestosterone therapy were acne in 6% of the patients, mild hirsutism in 3%, and an occasional delay in ovulation.

Adult↗