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Biomedical subjects

K M May

Publications and source records attributed to K M May.

At least 19 recordsLinked to original sources
PubMed2001

Two type V myosins with non-overlapping functions in the fission yeast Schizosaccharomyces pombe: Myo52 is concerned with growth polarity and cytokinesis, Myo51 is a component of the cytokinetic actin ring.

The fission yeast genome project has identified five myosin genes: one type I myosin, myo1(+), two type II myosins, myo2(+) and myp2(+), and two type V myosins, myo51(+) and myo52(+). Cells deleted for myo51(+) show normal morphology and growth rates whereas deletion of myo52(+) results in a partial loss of cell polarity, slow growth and cytokinetic defects. Combining both deletions in a single strain is phenotypically non-additive, myo52(delta) being epistatic to myo51(delta). Overproduction of Myo51 gives rise to elongated cells which fail to form functional septa whereas overproduction of Myo52 results in branched cells with aberrant septa that fail to cleave. Myo52 localises to the poles of growing cells but during cell division it relocalises to the cell equator as a bar that is bisected by the cytokinetic septum. Myo51 shows no obvious localisation during interphase but at cytokinesis it is associated with the contractile cytokinetic actin ring (CAR). Both myosins are dependent upon an intact actin cytoskeleton for localisation. Myo52 partially colocalises with the (alpha)-glucan synthase Mok1 at the cell tips and to a lesser extent at the septum. Mok1 is delocalised and upregulated in myo52(delta) and myo52(delta) cell walls are resistant to digestion by the cell wall degrading enzyme zymolyase. Thus myo52(+) appears to be involved in the local delivery or positioning of vesicles containing cell wall precursors at the cell tips and has a role in the maturation or cleavage of the septum. Myo51 has a non-essential role in cytokinesis as a component of the cytokinetic actin ring.

Actins↗
PubMed2000

A new genetic method for isolating functionally interacting genes: high plo1(+)-dependent mutants and their suppressors define genes in mitotic and septation pathways in fission yeast.

We describe a general genetic method to identify genes encoding proteins that functionally interact with and/or are good candidates for downstream targets of a particular gene product. The screen identifies mutants whose growth depends on high levels of expression of that gene. We apply this to the plo1(+) gene that encodes a fission yeast homologue of the polo-like kinases. plo1(+) regulates both spindle formation and septation. We have isolated 17 high plo1(+)-dependent (pld) mutants that show defects in mitosis or septation. Three mutants show a mitotic arrest phenotype. Among the 14 pld mutants with septation defects, 12 mapped to known loci: cdc7, cdc15, cdc11 spg1, and sid2. One of the pld mutants, cdc7-PD1, was selected for suppressor analysis. As multicopy suppressors, we isolated four known genes involved in septation in fission yeast: spg1(+), sce3(+), cdc8(+), and rho1(+), and two previously uncharacterized genes, mpd1(+) and mpd2(+). mpd1(+) exhibits high homology to phosphatidylinositol 4-phosphate 5-kinase, while mpd2(+) resembles Saccharomyces cerevisiae SMY2; both proteins are involved in the regulation of actin-mediated processes. As chromosomal suppressors of cdc7-PD1, we isolated mutations of cdc16 that resulted in multiseptation without nuclear division. cdc16(+), dma1(+), byr3(+), byr4(+) and a truncated form of the cdc7 gene were isolated by complementation of one of these cdc16 mutations. These results demonstrate that screening for high dose-dependent mutants and their suppressors is an effective approach to identify functionally interacting genes.

Amino Acid Sequence↗
PubMed1999

Campomelic syndrome and deletion of SOX9.

The human SOX9 gene, located in chromosome region 17q24.1-25.1, encodes a transcription factor involved in chondrogenesis and testis development. Mutations in this gene cause campomelic syndrome (CMPS) with autosomal sex reversal. Here we describe an infant girl with CMPS and an interstitial deletion on the long arm of chromosome 17 (46,X,del(17)(q23.3q24.3). The extent of SOX9 deletion on one chromosome 17 was defined using unique sequence fluorescent in situ hybridization probes. This is the first report of a patient with CMPS bearing a complete deletion of one SOX9 gene, and as such is the strongest evidence to date for dose-dependent action of the SOX9 protein in normal chondrogenesis.

Bone Diseases, Developmental↗
PubMed1999

Molecular refinement of the 1p36 deletion syndrome reveals size diversity and a preponderance of maternally derived deletions.

The deletion of chromosome 1p36 is a newly recognized, relatively common contiguous gene deletion syndrome with a variable phenotype. The clinical features have recently been delineated and molecular analysis indicates that the prevalence of certain phenotypic features appears to correlate with deletion size. Phenotype/genotype comparisons have allowed the assignment of certain clinical features to specific deletion intervals, significantly narrowing the regions within which to search for candidate genes. We have extensively characterized the deletion regions in 30 cases using microsatellite markers and fluorescence in situ hybridization analyses. The map order of 28 microsatellite markers spanning the deletion region was obtained by a combination of genotypic analysis and physical mapping. The deletion region was divided into six intervals and breakpoints were found to cluster in mainly two regions. Molecular analysis of the deletions showed that two patients had complex re-arrangements; these cases shared their distal and proximal breakpoints in the two common breakpoint regions. Of the de novo deletions ( n = 28) in whichparental samples were available and the analysis was informative ( n = 27), there were significantly morematernally derived deletions ( n = 21) than paternally derived deletions ( n = 6) (chi1(2) = 8.35, P < 0.0001). Phenotype/genotype correlations and refinements of critical regions in our naturally occurring deletion panel have delineated specific areas in which to focus the search for the causative genes for the features of this syndrome.

Chromosome Aberrations↗
PubMed1998

Yeast myosin II: a new subclass of unconventional conventional myosins?

Myosin II is the founder member of a large and structurally diverse clan of actin-based motor proteins. The native myosin II molecule is a hexamer consisting of two heavy chains, two essential light chains (ELC), and two regulatory light chains (RLC). For convenience, the myosin IIs are often subdivided into four subclasses: vertebrate skeletal and cardiac muscle myosin II form one subclass, vertebrate smooth muscle and nonmuscle myosin II a second, invertebrate muscle a third, and protozoan myosin II a fourth [Sellers and Goodson, 1995]. Different mechanisms of regulation may exist between myosins within a single subclass yet all myosin IIs share a common three-domain structure; the N-terminus of the heavy chain forms two globular heads that contain the ATP- and actin-binding sites and the alpha-helical neck region that is stabilised by the binding of the two classes of light chains, whilst the C-terminus forms an extended coiled-coil tail that can consist of anywhere between 700 and 1,200 amino acids. In nonmuscle cells, myosin II has at least two well-defined functions, cell locomotion and cytokinesis. Yeast cells do not locomote, and their mechanism of cytokinesis involves the deposition of a cross-wall or septum. However, in the fission yeast, Schizosaccharomyces pombe, deposition of the septum is anticipated by the appearance of a contractile actomyosin ring [Marks and Hyams, 1985; May et al., 1997; Kitayama et al., 1997] and actin is also present at the bud neck during cytokinesis in the budding yeast, Saccharomyces cerevisiae [Kilmartin and Adams, 1984]. Here we report a phylogenetic analysis of the N-terminal head domains of the myosin IIs from both yeasts, a structural analysis of the tail domains of these proteins and we speculate as to the nature of the light chains that regulate their function. On the basis of these findings, we propose that the yeast myosin IIs constitute a divergent fifth class of "unconventional" conventional myosins.

Amino Acid Sequence↗
PubMed1998

The myosin ATPase inhibitor 2,3-butanedione-2-monoxime (BDM) inhibits tip growth and cytokinesis in the fission yeast, Schizosaccharomyces pombe.

The growth of fission yeast cultures was reversibly inhibited by exposure to the myosin-ATPase inhibitor 2,3-butanedione-2-monoxime (BDM). Wild-type cells treated with 20 mM BDM for approximately two generation times were smaller than untreated controls and had a septation index approximately twice that seen in the absence of the inhibitor. The organization of actin at the cell poles was somewhat disorganized in the presence of BDM; however, cells formed a cytokinetic actin ring. When nitrogen-starved stationary-phase cells were reinoculated into fresh medium in the presence of BDM, the time taken to repolarize the actin cytoskeleton and to resume the characteristic vegetative cell shape before initiation of the first cell division were both substantially delayed. BDM significantly inhibited the increase in cell length of cdc25.22 cells arrested for cell cycle progress by incubation at the restrictive temperature and substantially delayed the initiation of both mitosis and cytokinesis in arrested cdc25.22 cells after release of the temperature block. These results suggest that tip growth and cytokinesis--processes in fission yeast that involve the actin cytoskeleton--also require myosin activity.

Actins↗
PubMed1998

Demographic and health status indicators to guide health promotion for Hispanic and Anglo rural elderly.

Naturally occurring differences rather than simple breakdowns by ethnic category are being used to tailor strategies in a three year senior community health worker-delivered health promotion intervention. A survey conducted of persons 60 and over in a rural southwestern U.S. community identified New Anglos (recent settlers, n = 264), Old Anglos (long-time residents, n = 298) and Hispanics (n = 236) for a total of 798 persons. Significant demographic differences included less education, poorer health status and more chronic conditions among Hispanics. Low rates of screening were the norm but especially severe among Old Anglos. Patterned differences in health practices, as well as group variations in use of resources and sources of information, revealed New Anglos used a larger variety of services and media. Generally, adjustments being made are related to Hispanic culture, cosmopolitan orientation of the New Anglos, and long-term isolation from information and services for Old Anglos.

Aged↗
PubMed1997

Type II myosin involved in cytokinesis in the fission yeast, Schizosaccharomyces pombe.

We have cloned an unique gene encoding the heavy chain of a type II myosin in the fission yeast, Schizosaccharomyces pombe. The myo2+ gene encodes a protein of 1526 amino acids with a predicted molecular weight of 177 kDa and containing consensus binding motifs for both essential and regulatory light chains. The S. pombe myo2+ head domain is 45% identical to myosin IIs from Saccharomyces cerevisiae and Homo sapiens and 40% identical to Drosophila melanogaster Structurally, myo2+ most closely resembles budding yeast MYO1, the tails of both myosin IIs containing a number of proline residues that are predicted to substantially disrupt the ability of these myosins to form coiled coils. The myo2+ gene is located on chromosome III, 8.3 map units from ade6+. Deletion of approximately 70% of the coding sequence of myo2+ is lethal but myo2delta spores can acquire a suppressor mutation that allows them to form viable microcolonies consisting of filaments of branched cells with aberrant septa. Overexpression of myo2+ results in the inhibition of cytokinesis; cells become elongated and multinucleate and fail to assemble a functional cytokinetic actin ring and are either aseptate or form aberrant septa. These results suggest that a contractile actin-myosin based cytokinetic mechanism appeared early in the evolution of eukaryotic cells and further emphasise the utility of fission yeast as a model organism in which to study the molecular and cellular basis of cytokinesis.

Amino Acid Sequence↗
PubMed1996

Sex ratios in fetuses and liveborn infants with autosomal aneuploidy.

Ten data sources were used substantially to increase the available data for estimating fetal and livebirth sex ratios for Patau (trisomy 13), Edwards (trisomy 18), and Down (trisomy 21) syndromes and controls. The fetal sex ratio estimate was 0.88 (N = 584) for trisomy 13, 0.90 (N = 1702) for trisomy 18, and 1.16 (N = 3154) for trisomy 21. All were significantly different from prenatal controls (1.07). The estimated ratios in prenatal controls were 1.28 (N = 1409) for CVSs and 1.06 (N = 49427) for amniocenteses, indicating a clear differential selection against males, mostly during the first half of fetal development. By contrast, there were no sex ratio differences for any of the trisomies when comparing gestational ages < 16 and > 16 weeks. The livebirth sex ratio estimate was 0.90 (N = 293) for trisomy 13, 0.63 (N = 497) for trisomy 18, and 1.15 (N = 6424) for trisomy 21, the latter two being statistically different than controls (1.05) (N = 3660707). These ratios for trisomies 13 and 18 were also statistically different than the ratio for trisomy 21. Only in trisomy 18 did the sex ratios in fetuses and livebirths differ, indicating a prenatal selection against males > 16 weeks. No effects of maternal age or race were found on these estimates for any of the fetal or livebirth trisomies. Sex ratios for translocations and mosaics were also estimated for these aneuploids. Compared to previous estimates, these results are less extreme, most likely because of larger sample sizes and less sample bias. They support the hypothesis that these trisomy sex ratios are skewed at conception, or become so during embryonic development through differential intrauterine selection. The estimate for Down syndrome livebirths is also consistent with the hypothesis that its higher sex ratio is associated with paternal nondisjunction.

Adult↗
PubMed1996

Asplenia syndrome in a child with a balanced reciprocal translocation of chromosomes 11 and 20 [46,XX,t(11;20)(q13.1;q13.13)].

We present a 6-year-old girl with a balanced 11;20 translocation [46,XX,t(11;20)(q13.1;q13.13)pat], asplenia, pulmonic stenosis, Hirschsprung disease, minor anomalies, and mental retardation. This case represents the second report of an individual with situs abnormalities and a balanced chromosome rearrangement involving a breakpoint at 11q13. Polymerase chain reaction (PCR) analysis of microsatellite markers excluded uniparental disomy for chromosomes 11 and 20. Segregation analysis of markers in the 11q13 region in the proposita and her phenotypically normal carrier sibs did not show a unique combination of maternal and paternal alleles in the patient. We discuss several possible explanations for the simultaneous occurrence of situs abnormalities and a balanced 11;20 translocation. These include (1) chance, (2) a further chromosome rearrangement in the patient, (3) gene disruption and random situs determination, and (4) gene disruption plus transmission of a recessive or imprinted allele from the mother.

Abnormalities, Multiple↗
PubMed1996

Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II.

The cause of non-disjunction of chromosome 21 remains largely unknown. Advanced maternal age is associated with both maternal meiosis I (MI) and meiosis II (MII) non-disjunction events. While reduced genetic recombination has been demonstrated in maternal MI errors, the basis for MII errors remains uncertain. We studied 133 trisomy 21 cases with maternal MII errors to test the hypothesis that segregation at MII may also be influenced by genetic recombination. Our data support a highly significant association: MII non-disjunction involves increased recombination that is largely restricted to proximal 21q. Thus, while absence of a proximal recombination appears to predispose to non-disjunction in MI, the presence of a proximal exchange predisposes to non-disjunction in MII. These findings profoundly affect our understanding of trisomy 21 as they suggest that virtually all maternal non-disjunction results from events occurring in meiosis I.

Adult↗
PubMed1995

Community empowerment in rural health care.

The Healthy Communities 2000 mandate calls for public health leaders to involve community members in setting health priorities and implementing programs in response to the national health objectives for the year 2000 (American Public Health Association, 1991). This paper describes community involvement through a community empowerment nursing intervention and evaluates its application in a rural community. A community health nursing project (AHCPR, Grant No. HS06801) with three interventions, one of which was community empowerment, was designed to address the health needs of small, rural, underserved, primarily Mexican American communities in Arizona. Community empowerment in this project was based on the community-development approach to community organization, and involved community health nurses and lay health workers, called promotoras, who are key persons in community development. The implementation of two health fairs, one the result of the community-empowerment intervention, is described and evaluated in relation to community health. The community-empowerment intervention was based on community participation and responsibility, hallmarks of the second health fair, reflecting lay expertise and cooperation among various levels of the community. Successes and limitations of the health fairs provide feedback for developing a community-empowerment intervention.

Arizona↗
PubMed1994

Health education for homeless populations.

There is little reported in the literature regarding evaluation of health education for homeless populations. In a program for health education of the homeless in shelters, volunteer instructors, including nurses, provided classes on health promotion, prevention, and self-care for homeless clients at 13 urban shelters and treatment sites since 1991. Program evaluation was done through a survey of clients (N = 1,202) attending classes. Based on analysis of evaluation results for 18 months, it was found that 50 volunteer instructors, most of whom were nurses, covered 49 health topics in 176 classes. Clients found the classes helpful and expressed preferences for future topics (e.g., stress and self-esteem). Perceived ability to discuss was related to group size and shelter composition (women only vs. women and men). Survey results provided feedback for program development.

Adaptation, Psychological↗
PubMed1993

Paternal uniparental disomy in a child with a balanced 15;15 translocation and Angelman syndrome.

Chromosome 15 (15q11-q13) abnormalities cause two distinct conditions, Angelman syndrome (AS) and Prader-Willi syndrome (PWS). We present the first case of a child with a balanced 15;15 translocation and AS in whom molecular studies were crucial in confirming a diagnosis. DNA polymorphisms demonstrated paternal uniparental disomy for chromosome 15, consistent with the diagnosis of AS. The molecular studies also showed the patient to be homozygous at all loci for which the father was heterozygous, suggesting that the structural rearrangement was an isochromosome 15q and not a Robertsonian translocation.

Angelman Syndrome↗
PubMed1992

Middle-Eastern immigrant parents' social networks and help-seeking for child health care.

The purpose of this research was to describe: (a) Arab-American immigrant parents' perceptions of their social networks, including social support; and (b) Arab-American immigrant parents' perceptions of their help-seeking related to child health care. Seventy-three immigrant parents who were Egyptian-American (n = 17), Palestinian-American (n = 44) and Yemeni-American (n = 12) completed the Norbeck Social Support Questionnaire, four Supplementary Social Support Questions, a Support System Map and a Child Health Interview Guide. Family and relatives were perceived as the major source of support and comprised the highest percentage of social network members. Compared with published scores of a normative American sample, the immigrant parents' scores were lower (P less than 0.01) on all social network and social support variables. There was a moderate negative correlation (r = 0.47) between parents' number of years of residence in the USA and percentage of network members living outside the USA (P less than 0.01) and a weak positive correlation (r = 0.36) between number of years in the USA and percentage of network members living close to the parent (P less than 0.01). Parents' help-seeking for child health care involved use of a variety of resources, with reliance on some long-distance support from family in the Middle-East. This descriptive research provides a basis for further research on patterns of support and help-seeking in immigrant parents.

Adolescent↗
PubMed1991

Preventing low birth weight: marketing and volunteer outreach.

Low birth weight (LBW) contributes to infant mortality and continues to be a public health concern in the United States. A community-based prenatal program was established to prevent low birth weight through early and continuous prenatal care. Two key dimensions of the program were marketing and the use of volunteer neighborhood outreach workers. This paper explores the role of the program's public health nurses in relation to these dimensions and makes recommendations regarding marketing and use of outreach workers.

Arizona↗