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Biomedical subjects

P T Rowley

Publications and source records attributed to P T Rowley.

At least 73 records · Page 4Linked to original sources
PubMed1984

Genetic screening: marvel or menace?

Genetic screening is a systematic search in the population for persons of certain genotypes. The usual purpose is to detect persons who themselves or whose offspring are at risk for genetic diseases or genetically determined susceptibilities to environmental agents. Is genetic screening a marvel about to free us from the scourge of genetic disease or a menace about to invade our privacy and determine who may reproduce? There are three different types of genetic screening. Newborn screening identifies serious genetic disease at birth, permitting prompt treatment to prevent mental and physical retardation. Fetal screening and prenatal diagnosis identify genetic disease in the fetus permitting selective termination of pregnancy and the opportunity to have children free of defects detectable in utero. Carrier screening identifies individuals heterozygous for a gene for a serious recessive disease who may be at risk for affected offspring. The challenge to society is to provide (by way of cost-effective programs) expert services, including genetic counseling and follow-up, to all who may benefit, to ensure confidentiality and freedom of choice, and to avoid misunderstanding and stigmatization. It is recommended that the objective of screening programs should be to maximize the options available to families at risk rather than to reduce the incidence of genetic diseases. Whenever possible, the providers of these services should be the providers of primary health care. Urgently needed are a greater awareness of avoidable genetic diseases on the part of primary care providers and efforts to familiarize the public with the basic concepts of human genetics through the public school system.

Amniocentesis↗
PubMed1984

K562 human leukemia cell passages differ in embryonic globin gene expression.

K562 is a human leukemia cell line inducible by a variety of agents for the synthesis of embryonic and fetal hemoglobins. We compared early and late passages to determine whether a change has occurred in globin synthetic pattern. Clone LA4, derived from passage 199 which had been frozen by Lozzio in 1973, was compared with clone RA6, derived from a line received from Rutherford in 1979. Globin synthetic pattern was determined by incubation with [3]leucine, separation of globins by Triton-X100 polyacrylamide gel electrophoresis, and analysis by fluorography. For RA6, hemin-induced synthesis was greatest for zeta globin but minimal for epsilon globin, whereas for LA4 it was greatest for epsilon globin but minimal for zeta globin. Both lines are pseudotriploid with three No. 11 and three No. 16 chromosomes. However only RA6 has a translocation involving the short arm of chromosome 11 which contains the locus of the beta globin gene cluster. However, translocation-associated deletion does not simply explain the deficient inducibility of epsilon synthesis because G gamma and A gamma globins, whose genes are linked to the epsilon gene, are similarly inducible in the two lines.

Animals↗
PubMed1984

K562 human erythroleukemia cell variants resistant to growth inhibition by butyrate have deficient histone acetylation.

K562 is an established human erythroleukemia cell line, inducible for hemoglobin synthesis by a variety of compounds including n-butyrate. To elucidate the role of butyrate-induced histone acetylation in the regulation of gene expression in K562 cells, we isolated 20 variants resistant to the growth inhibitory effect of butyrate. Four variants having different degrees of resistance were selected for detailed study. All four were found to be resistant to the hemoglobin-inducing effect of butyrate, suggesting that the two aspects of butyrate response, restriction of growth and induction of hemoglobin synthesis, are coupled. Further, after (5 days) culture with butyrate, two of the four variants exhibit less acetylation of H3 and H4 histones than does the butyrate-treated parent. Analysis of histone deacetylases from the variants indicated that each variant was distinct and that butyrate resistance may be accounted for by decreased affinity of the variant enzymes for butyrate, increased affinity of the enzymes for acetylated histone, or both. The fact that variants selected for resistance to growth inhibition by butyrate are also deficient in butyrate-induced hemoglobin synthesis and have abnormal histone deacetylase activity argues for butyrate inducing K562 cells to synthesize hemoglobin and restrict growth via histone acetylation.

Acetylation↗
PubMed1984

Screening and genetic counseling for beta-thalassemia trait in a population unselected for interest: comparison of three counseling methods.

We have assessed the effects of screening and genetic counseling for beta-thalassemia trait on knowledge, attitudes, and behavior in a prospective, controlled study of randomly selected adult members of a health maintenance organization. We report here that knowledge of manifestations and of inheritance of thalassemia, previously reported to be high immediately after counseling, were well maintained at 2 and 10 months following counseling. There was no detectable impairment of self-concept. Marital adjustment improved, and sexual activity increased significantly. Mood, assessed immediately before and after counseling, showed no undesirable changes. A patient-structured counseling method, designed to minimize negative psychological effects via discussion of feelings, was not superior to conventional and programmed methods, described in our previous reports, in terms of learning or attitude change.

Adolescent↗
PubMed1983

Newborn sickle cell screening. Benefits and burdens realized.

Seventeen newborns identified by state-mandated screening as having sickle cell disease or homozygous hemoglobin C disease were followed up through interviews of their physicians and their parents to assess benefits and burdens received by the families. Many parents had provided proper care for their children (12/17) and pneumococcal prophylaxis had been given (6/14). However, some parents did not understand the recurrence risk (3/11) and for others genetic counseling may have threatened the parental relationship by focusing attention on the identity of the father (3/11). Deriving the maximum benefit from newborn sickle cell screening will require a better understanding on the part of physicians of the differential diagnosis, treatment, and inheritance of sickle cell disease and guidance regarding comprehensive counseling of families. In the meantime, states mandating such screening need to provide individual case follow-up.

Anemia, Sickle Cell↗
PubMed1983

Erythroleukemia manifesting delta beta-thalassemia.

A 27 year old male with aplastic anemia developed a high fetal hemoglobin, a low hemoglobin A2, a decreased beta/alpha synthetic ratio, and an increased G gamma/A gamma synthetic ratio. This acquired hemoglobinopathy resembling delta beta-thalassemia was recognized at the onset of acute erythroleukemia. Certain features of this abnormal globin synthetic pattern resemble those of the normal fetus and thus appear to provide another example of gene expression by malignant cells resembling that of an earlier stage of the organism's development.

Adult↗
PubMed1982

Newborn screening for hemoglobinopathies in New York State: experience of physicians and parents of affected children.

Responses of physicians and parents to New York State-mandated newborn screening for sickle cell disease were solicited and evaluated. The index group comprised 25 infants born in western upstate New York. Each was found to have either sickle cell disease, hemoglobin SC disease, sickle beta-thalassemia, or hemoglobin C disease. In nondirective interviews the following factors were assessed: clinical course, the physician's policies of disease treatment and family counseling, the parents' reactions to the diagnosis and their level of understanding and compliance with medical recommendations, and the physicians' and parents' views on newborn screening. Newborn screening for sickle hemoglobin makes early prophylaxis and prompt treatment possible. Some morbidity may have been averted, judging from parental understanding of medical needs. Parents and physicians agreed that newborn screening for hemoglobinopathies is a valuable public health program. Suggestions for improving the New York state program included a need to increase communication among the screening laboratory, the hospital, and the physician; encouraging physicians to educate parents more fully, provide genetic counseling, and test parents and siblings of the identified neonate; and, most important, provide a well-delineated mechanism for follow-up of every infant with a potentially symptomatic hemoglobinopathy.

Age Factors↗
PubMed1982

Hemin preferentially stimulates synthesis of alpha-globin in K562 human erythroleukemia cells.

K562 human erythroleukemia cells are an established cell line derived from an adult with chronic myelogenous leukemia. Hemin stimulates their synthesis of embryonic and fetal hemoglobins. We have found that their globin synthetic pattern depends on the concentration of added hemin. Clone RA6 was cultured with 0--100 microM hemin and the globin synthetic pattern determined by 3H-leucine incorporation and analysis of 3H-globins by polyacrylamide gel electrophoresis in Triton X acid urea followed by fluorography and densitometry. The higher the hemin concentration, the greater the synthetic rate of each type of globin. However, the relative increase was greatest for alpha-globin. We propose that the differential dependence of alpha synthesis on added hemin is a reflection of translational inefficiency of alpha messenger RNA and that this property is exposed when the translational capacity of the cell is limited by hemin deficiency. We suggest that the differential dependence of alpha-chain synthesis on added hemin in clone RA6 is evidence of an intrinsic deficiency in heme synthesis.

Cell Line↗
PubMed1981

Assessment of evaluation of hospitalized pediatric patients with genetic disorders.

A survey of the status of pediatric and neonatal care in a university general hospital was conducted for a 12-month period in order to define existing needs and plan for improved inpatient genetic management. The records of 218 patients with one of 22 specified disorders were reviewed to evaluate the nature of documented genetic considerations and formulated dispositions during hospitalization. The 22 clinical entities were classified as chromosomal, single-gene, polygenic, or possibly genetic. In 15.1 per cent of cases the need for genetic counseling was recognized and recorded on the patient's chart. Sixteen of the 218 records (7.3%) met the minimum criteria for a "genetic disposition." Suggestions for improving the hospital clinical management of patients with genetic disorders are presented.

Adolescent↗
PubMed1981

Inducers of erythroid differentiation in K562 human leukemia cells.

A variety of agents, including many known to induce erythroid differentiation in Friend murine erythroleukemia cells, were tested for their ability to induce erythroid differentiation in K562 humane erythroleukemia cells. Cells were grown in suspension culture and scored for erythroid differentiation by benzidine staining. Of 39 agents tested, 19 induced erythroid differentiation in K562 cells and 20 did not. A striking effect of the type of serum employed in the medium was observed. The majority of the agents inducing erythroid differentiation in medium containing fetal calf serum showed little activity in medium containing newborn calf serum.

Animals↗
PubMed1981

Genetic counseling for beta-thalassemia trait following health screening in a health maintenance organization: comparison of programmed and conventional counseling.

Providing adequate counseling of patients identified in genetic screening programs is a major responsibility and expense. Adults in a health maintenance organization, unselected for interest, were screened for beta-thalassemia trait as part of preventive health care. Counseling was provided by either a trained physician (conventional counseling) or by a videotape containing the same information followed by an opportunity to question a trained physician (programmed counseling). Immediately before and after counseling, knowledge of thalassemia, knowledge of genetics, and mood change were assessed by questionnaire. Comparable mood changes and similar learning about thalassemia and genetics occurred with both counseling methods. Thus, as judged by immediate effects on knowledge and mood, videotaped instruction can greatly reduce professional time required for genetic counseling and facilitate the incorporation of genetic screening into primary health care.

Adult↗
PubMed1981

Erythropoiesis in vitro: enhancement by neuraminidase.

Neuraminidase treatment of human fetal liver or adult marrow cells prior to culture results in an increased number of erythroid colonies and bursts. No increase occurs in the number of nonerythroid colonies. The number of bursts having more than eight subunits is increased preferentially. Individual burst subunits are also enlarged. Neuraminidase-treated cells yield erythroid bursts when cultured in concentrations of erythropoietin insufficient to produce bursts from untreated cells. It is proposed that (1) neuraminidase treatment of adult and fetal cell mixtures specifically stimulates differentiation of erythroid precursors, (2) the preferential stimulation of erythroid bursts having many subunits suggests a preferential susceptibility of more primitive BFU-Es, and (3) neuraminidase treatment enhances the response of erythroid precursors to erythropoietin.

Bone Marrow↗
PubMed1980

Trypsin enhances erythropoiesis in vitro.

When a single cell suspension of human adult marrow or fetal liver is treated briefly with trypsin, the number of erythroid bursts arising in culture is significantly increased. Erythroid colonies show less stimulation. The time to reach maximum burst number may also be shortened. The absolute increase in burst number is greater at higher concentrations of erythropoietin, suggesting a synergistic effect of trypsin treatment with that of erythropoietin. Trypsin also increases the size of the individual burst subunit. The trypsin effect is not limited to a given class of bursts as distinguished by subunit number. Other enzymes, pronase, chymotrypsin and phospholipase D, also increase burst number but to a lesser degree. The burst-stimulating effect of trypsin is enzymatic since it is completely prevented by DFP, a specific inhibitor of trypsin action.

Adult↗
PubMed1979

Sickle cell trait/hereditary persistence of fetal hemoglobin trait. Misdiagnosis as sickle cell anemia by newborn screening.

A black female infant, reported as a result of mandatory newborn screening to have sickle cell anemia, was found at 8 months of age to have instead the entirely benign disorder sickle cell trait/hereditary persistence of fetal hemoglobin trait. The finding of hemoglobin S without Hb A does not suffice for the diagnosis of homozygous Hb S. Screening programs that diagnose sickle cell aneimia without first demonstrating sickle hemoglobin in both parents will consistently misdiagnose several more benign hemoglobin states as sickle cell anemia.

Anemia, Sickle Cell↗
PubMed1979

Acquired hemoglobin H disease in idiopathic myelofibrosis.

A 68-year-old male, diagnosed 1 year previously as having myelofibrosis, developed hemolysis, red cell inclusions, and 37% Hb H. The alpha/beta globin synthetic ratio for circulating reticulocytes, determined by 3H-leucine incorporation and globin chain separation by carboxymethylcellulose chromatography in urea, was 0.049. When total RNA was purified from peripheral blood cells and translated in a wheat germ cell-free translation system, the alpha/beta ratio of the translation products was 0.26, indicating mRNA as a major cause of the globin synthetic imbalance. This study demonstrates that myelofibrosis is one setting in which acquired Hb H disease occurs; that the synthetic imbalance may be extreme; and that it can be associated with an imbalance in the activities of specific globin mRNAs.

Aged↗
PubMed1979

Hemoglobin synthesis in cultures of hepatic erythroid cells from the human fetus.

A recent theory of the control of human fetal hemoglobin synthesis, based on studies in cultured adult marrow, proposes that the phenotypic expression of fetal hemoglobin is largely dependent on the level of differentiation of the parental stem cells; that is, the earlier the progenitor, the greater the ability of its progeny to express fetal hemoglobin [Papayannopoulou, Th., Brice, M. & Stamatoyannopoulos, G. (1977) Proc. Natl. Acad. Sci. USA 74, 2923-2927]. To test this relationship with fetal tissue, we have studied hemoglobin synthesis in cultured human fetal liver, comparing gamma chain synthesis in the descendants of the early progenitors ("bursts") with that in the descendants of the later progenitors ("colonies"). Cells from the livers of midtrimester fetuses were cultured in methylcellulose with erythropoietin. The beta/(beta + gamma) globin synthetic ratio on days 5 to 7, when colonies predominated, was 0.09-0.11, a value characteristic of fetal reticulocytes, and on days 11 and 12, when bursts predominated, was 0.15-0.17. Thus, in fetal liver, the descendants of the earlier progenitor, the burst-forming unit, may be making more beta chains rather than more gamma chains, compared to descendants of the later progenitor, the colonyforming unit. Our data on fetal liver, taken together with the data on adult marrow by others, suggest that the erythroid colonies express the gene characteristic of the age of the organism to a greater degree than bursts, which express beta and gamma genes less specifically. Thus, the capacity for highly selective gene expression characteristic of differentiated cells appears to be less well developed in the burst-forming unit than in the colony-forming unit.

Cells, Cultured↗