Regression of gastric large B-Cell lymphoma accompanied by a florid lymphoma-like T-cell reaction: immunomodulatory effect of Ganoderma lucidum (Lingzhi)?

Complete regression of high-grade lymphoma is extremely rare. We report 1 such case that might have been conceivably mediated by Ganoderma lucidum (Lingzhi), an immunomodulatory herbal medicine. A 47-year-old man presented with epigastric pain. Endoscopy revealed a large gastric ulcer, which on biopsy was diagnostic of large B-cell lymphoma. At gastrectomy 11 days later, no evidence was found of large B-cell lymphoma despite thorough sampling. Instead, there was a dense and permeative infiltrate of CD3(+) CD8(+) cytotoxic small T lymphocytes spanning the whole thickness of the gastric wall. In situ reverse transcription polymerase chain reaction for T-cell receptor beta-chain family did not detect a monoclonal T-cell population. We postulate that the cytotoxic T cells may represent an active host-immune response against the large B-cell lymphoma that resulted in a complete regression. On questioning, the patient had taken megadoses of Ganoderma lucidum, which might have triggered the successful immune reaction.

Relations among physical activity, physical fitness, and self-perceived fitness in Hong Kong adolescents.

The relationships between physical fitness, activity, and self-perceived fitness in adolescents in Hong Kong were investigated. Regular physical activity patterns, self-perceptions of fitness, and health-related physical fitness were measured in 201 secondary school students (M age = 13.8 yr.). The battery of fitness tests measured cardiovascular capacity, flexibility, muscular strength, muscular endurance, and body fat composition. The boys had a higher self-perception of their own fitness and exercised more outside school than the girls. Participation in physical activity was related to cardiovascular capacity, muscular strength, and body composition. Linear regression analysis indicated that exercise activity and body composition explained a portion of variance in the subjects' self-perceived fitness. These findings highlight the connections between physical activity, fitness, and self-perception of fitness and consequently the need for understanding the concept for better health-promotion strategies.

Prevalence of human papillomavirus in cervical cancer: a multicenter study in China.

A large-scale epidemiologic survey on the prevalence of different types of human papillomavirus (HPV) in cervical cancer in China is indicated because of the implications for the development of diagnostic probes and vaccines against cervical cancer. A total of 809 cervical cancer specimens were collected from 5 regions in China including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. HPV DNA was detected in 83.7% of the specimens. HPV-16 was present in 79.6%, HPV-18 in 7.5%, HPV-52 in 2.6% and HPV-58 in 3.8% of all HPV-positive specimens. The prevalences of HPV-16 and HPV-18 in Hong Kong were 61.7 and 14.8%, respectively, representing a lower HPV-16 and a higher HPV-18 proportion compared with the other regions. HPV-16 remained the most common HPV infection in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). The proportion of HPV-18 infection was significantly higher in AC than in SCC.

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.

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.

Caregiving and help seeking by mothers of low birthweight infants and mothers of normal birthweight infants.

The purpose of this research was to describe perceptions of infant health, caregiving at home, and help seeking by mothers of low birthweight (LBW) infants (n = 30) and mothers of normal birthweight infants (n = 30). In this descriptive study, data were analyzed through multiple regression, t tests, and content analysis of responses to researcher-constructed questionnaires. There were statistically significant relationships between: infant health and both confidence in caregiving (R2 = 0.18, p<0.001) and caregiver burden (R2 = 0.29, p<0.001); preparation for caregiving and confidence in caregiving (R2 = 0.10, p<0.05); and confidence in caregiving and caregiver burden (R2 = 0.12, p<0.01). Compared with mothers of normal birthweight infants, mothers of LBW infants perceived poorer infant health, t (58) = -2.02, p = <0.05, and more caregiver burden, t (58) = 3.50, p = <0.001. Mothers reported seeking help from a variety of resources, mostly nonprofessional for questions on infant care or nonserious infant health problems, and mostly physicians for questions on serious infant health problems. Nurses can use knowledge of mothers' perceptions of infant health, caregiving, and help seeking to facilitate mothers' management of caregiving and resource use.

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.

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.

Detection of mosaicism in amniotic fluid cultures: a CYTO2000 collaborative study.

PURPOSE: To evaluate the assumptions on which the American College of Medical Genetics (ACMG) Standards and Guidelines for detecting mosaicism in amniotic fluid cultures are based. METHODS: Data from 653 cases of amniotic fluid mosaicism were collected from 26 laboratories. A chi-square goodness-of-fit test was used to compare the observed number of mosaic cases with the expected number based on binomial distribution theory. RESULTS: Comparison of observed data from the in situ colony cases with the expected distribution of cases detected based on the binomial distribution did not reveal a significant difference (P = 0.525). CONCLUSIONS: The empirical data fit the binomial distribution. Therefore, binomial theory can be used as an initial discussion point for determining whether ACMG Standards and Guidelines are adequate for detecting mosaicism.

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.

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.

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.

Searching for normalcy: mothers' caregiving for low birth weight infants.

This research addressed the process mothers use to seek help when giving care to low birth weight (LBW) infants at home. The design was descriptive, using a grounded theory approach. Data from audiotaped interviews guided by questions about seeking help related to giving care were analyzed by constant comparative analysis. The sample was 14 mothers of premature LBW infants enrolled in a follow up clinic for high risk infants. Their LBW infants (M birth weight = 1,575 g) were 4-12 months old (M = 9) at the time of the interview. Searching for Normalcy through caregiving includes: learning caregiving, maintaining vigilance for progress, normalizing going alone with caregiver burden, and help-seeking. Mothers seek resources for information, assessment and treatment, respite caregiving, and support. Nurses can help mothers identify, access, and effectively use resources.

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.

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.

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.

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.

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.

Exercise training and mouse mammary tumour metastasis.

The present study was designed to address whether exercise influences the experimental metastasis of a mouse mammary tumour; a related issue was the impact of timing of exercise onset relative to tumour exposure on NK and LAK mediated cytotoxicity. After 8 weeks of forced treadmill exercise or voluntary wheel running or remaining sedentary, female BALB/c mice received an intravenous (i.v.) injection of female BALB/c mice received an intravenous (i.v.) injection of MMT line 66 tumour cells. Mice were then randomized into continuation of activity (TT, WW), cessation of activity (TS, WS), initiation of activity (ST, SW) and maintenance of sedentary condition (SS) for three weeks. Tumour control (TC) mice, who were matched to the SS mice for age, received an i.v. injection of heat-killed MMT 66 tumour cells. In total there were 8 groups including the tumour control. The average number of lung tumours did not differ by activity condition; however, the mice in the continuous treadmill group (TT) tended to have a higher tumour multiplicity (162 +/- 22) and those in the treadmill x sedentary condition (TS) tended to have lower tumour multiplicity (109 +/- 16) compared with the other groups except the SW group (95 +/- 15). The lymphokine activated killer activity in the spleen was significantly elevated in the TS (49 +/- 3%) and WS (44 +/- 3%) mice compared with the sedentary animals (30 +/- 3%) (p < 0.003 and 0.05, respectively). NK activity was lower in the mice that had stopped exercising (TS and WS) after injection of tumour compared with sedentary animals. These data suggest that although exercise training influences natural immune cytotoxic mechanisms in vitro, this may not translate into clinically significant changes in tumour burden. The dissociation between natural immunity and tumour outcome may reflect the relative resistance of the tumour line to lysis by natural killer cells. It remains to be tested if infusion of IL-2 (to induce LAK activity) in exercise trained animals results in fewer tumour metastases.

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.