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Biomedical subjects

M Hughes

Publications and source records attributed to M Hughes.

At least 19 recordsLinked to original sources
PubMed1992

Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein (pIXY 321) enhances high-dose Ara-C-induced programmed cell death or apoptosis in human myeloid leukemia cells.

High dose Ara-C (HIDAC) induces programmed cell death (PCD) or apoptosis in vitro in human myeloid leukemia cells, which correlates with the inhibition of their clonogenic survival. Hematopoietic growth factors (HGFs) granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) have been demonstrated to enhance the metabolism and cytotoxic effects of HIDAC against leukemic progenitor cells. We examined the effect of pIXY 321 (a GM-CSF/IL-3 fusion protein) on HIDAC-induced PCD and related gene expressions as well as HIDAC-mediated colony growth inhibition of human myeloid leukemia cells. Unlike the previously described effects of HGFs on normal bone marrow progenitor cells, exposure to pIXY 321 alone for up to 24 hours did not suppress PCD in HL-60 or KG-1 cells. However, exposure to pIXY 321 for 20 hours followed by a combined treatment with Ara-C plus pIXY 321 for 4 or 24 hours versus treatment with Ara-C alone significantly enhanced the oligonucleosomal DNA fragmentation characteristic of PCD. This was temporally associated with a marked induction of c-jun expression and a significant decrease in BCL-2. In addition, the treatment with pIXY 321 plus HIDAC versus HIDAC alone produced a significantly greater inhibition of HL-60 colony growth. These findings highlight an additional mechanism of HIDAC-induced leukemic cell death that is augmented by cotreatment with pIXY 321 and may contribute toward an improved antileukemic activity of HIDAC.

Actins↗
PubMed1992

Paraneoplastic myelopathy at diagnosis in a patient with pathologic stage 1A Hodgkin disease.

The case of a patient with pathologic Stage 1A Hodgkin disease is reported in whom subacute paraneoplastic myelopathy developed before treatment. Myelography, computed tomography, magnetic resonance imaging, and lumbar puncture examination showed no evidence of central nervous system involvement. The patient was treated with combination chemotherapy (to avoid spinal cord exposure to radiation) without neurologic improvement. The patient's neurologic condition responded well to intrathecal dexamethasone.

Dexamethasone↗
PubMed1992

Acute stridor due to bilateral vocal fold paralysis as a presenting sign of myasthenia gravis.

We describe a case of myasthenia gravis in a 46-year-old man presenting as acute stridor with bilateral abductor paralysis of the vocal folds. Prompt diagnosis and medical treatment with pyridostigmine avoided the need for tracheostomy. It is important to remember the possibility of myasthenia gravis in cases of stridor due to bilateral vocal fold paralysis, since effective medical treatment is available.

Acute Disease↗
PubMed1992

Molecular biological approaches to the study of vectors in relation to malaria control.

To a large extent, control of malaria vectors relies on the elimination of breeding sites and the application of chemical agents. There are increasing problems associated with the use of synthetic insecticides for vector control, including the evolution of resistance, the high cost of developing and registering new insecticides and an awareness of pollution from insecticide residues. These factors have stimulated interest in the application of molecular biology to the study of mosquito vectors of malaria; focussing primarily on two aspects. First, the improvement of existing control measures through the development of simplified DNA probe systems suitable for identification of vectors of malaria. The development of synthetic, non-radioactive DNA probes suitable for the identification of species in the Anopheles gambiae complex is described with the aim of defining a simplified methodology which is suitable for entomologist in the field. The second aspect to be considered is the development of completely novel strategies through the genetic manipulation of insect vectors of malaria in order to alter their ability to transmit the disease. The major requirements for producing transgenic mosquitoes are outlined together with the progress which has been made to date and discussed in relation to the prospects which this type of approach has for the future control of malaria.

Animals↗
PubMed1992

Heterodimerization with c-Fos is not required for cell transformation of chicken embryo fibroblasts by Jun.

c-Jun belongs to a family of proteins that require dimerization for activity. Dimerization occurs through a leucine-rich region near the carboxy terminus called the leucine zipper. Jun can form dimeric complexes with other Jun family as well as Fos family members. The relative proportion of these different dimeric complexes is determined by the relative abundance of each family member at a particular time. Overexpression of v-Jun or c-Jun alone will lead to cell transformation of chicken embryo fibroblasts, albeit with varying efficiencies. Upon overexpression, v-Jun or c-Jun presumably becomes the predominant AP-1 component in the cell. Theoretically, this should lead to a larger proportion of homodimers than heterodimers. It is not clear what role, if any, the other Jun and Fos family proteins play during cell transformation. We have examined the ability of Jun to induce cell transformation in chicken embryo fibroblasts in the absence of interaction with other Jun or Fos family proteins. To this end, we have constructed a chicken v-Jun mutant that is incapable of heterodimerization. This was accomplished by replacing the leucine zipper region of Jun with that of the yeast transcription factor GCN4. This chimeric protein, VJ-GLZ, retains all of the DNA binding and transcriptional activation domains of v-Jun. As expected, in vitro translated VJ-GLZ was found to be incapable of forming heterodimers with c-Fos, FosB, and JunD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Antibodies and DNA probes used to analyze variant populations of the Indochina-1 strain of Plasmodium falciparum.

Ten variant populations derived from the Indochina-1 strain of Plasmodium falciparum were analyzed by using (i) hyperimmune serum raised against some of these populations in squirrel monkeys and (ii) an oligonucleotide probe based on the rep-20 sequence, which had previously been shown to be a useful marker of diversity. Although all 10 subpopulations had an identical fingerprint pattern on Southern blots probed with the oligonucleotide, thus demonstrating a homogeneous genetic makeup, they all had a different phenotype for erythrocyte-associated antigens, thus confirming serological variant-specific differences. Antibodies to erythrocyte-associated antigens were measured with a new technique including immunogold and silver enhancement. The results of this study indicate that antigenic variation can occur without major genomic reorganization.

Animals↗
PubMed1990

Tissue specific expression of avian vitellogenin gene is correlated with DNA hypomethylation and in vivo specific protein-DNA interactions.

The avian vitellogenin gene is expressed only in the liver of egg-laying hens. It can, however, be activated in immature chicks or roosters by oestradiol. Parallel to the onset of transcription, there is a demethylation of specific mCpGs in the promoter region and in the oestrogen response element (ERE). The methylation pattern in the promoter region is hormone and expression specific, whereas in the ERE it is only hormone and not organ specific. The demethylation occurring in the promoter region is correlated with the appearance of DNase I hypersensitivity sites and changes in the specific protein-DNA interactions. In vivo genomic footprinting of the ERE with varying concentrations of dimethylsulphate revealed, upon gene activation, only minor changes in the protein-DNA interaction. We present evidence that there is another protein that binds with high affinity to the ERE, besides the oestrogen receptor.

Animals↗
PubMed1990

Williams syndrome in twins.

Two sets of identical twins with Williams syndrome have been reported previously. We report on 2 additional sets of presumed identical twins with Williams syndrome. All 4 patients had the typical Williams syndrome facial appearance, growth deficiency, and developmental delay. None of the patients had supravalvular aortic stenoses; however, all were diagnosed as having probable distal pulmonary artery stenosis. In the set of twins in which serum calcium was measured, one twin had an elevated serum ionized calcium level. These 2 sets of twins further document the occurrence of Williams syndrome in identical twins. To our knowledge, there are no reported cases of concordance in dizygotic twins. This adds further support to the likelihood that Williams syndrome is a genetic disorder.

Abnormalities, Multiple↗
PubMed1989

The effects of multivitamins and minerals on children with Down syndrome.

The effects of high-dosage multivitamin and mineral supplements on 15 children with Down syndrome aged between 7.5 and 63 months were studied in a placebo-controlled crossover trial. Active treatment was associated with decreased developmental progress, and various side-effects were reported by the parents. The only suggestions of benefit were parents' observations of improvement in general appearance and skin freshness. However, the parents were willing to continue using the treatment and to recommend it to other parents, despite the side-effects.

Child, Preschool↗
PubMed1989

Long-term prognosis after resuscitation from primary ventricular fibrillation complicating acute transmural myocardial infarction in the north east of Scotland.

The aim of this study is to determine the long-term prognosis of patients successfully resuscitated from primary ventricular fibrillation in the acute phase of transmural myocardial infarction and to identify predictors of mortality. Details of 75 consecutive patients between October 1971 and May 1981 were reviewed in October 1985. The cumulative survival rates at one year, two year, five year and 10 year were 84%, 77% 67% and 40.5% respectively with a median survival time of 8.7 years. Univariate and Cox survival analyses were used to determine predictors of mortality. Only the age of the patient at the time of infarction was found to be highly significant with a greatly increased mortality rate in the older age group (p less than 0.001). The sex, site of infarction (anterior or inferior) and time of entry in the study did not significantly influence long-term prognosis.

Adult↗
PubMed1989

The influence of type of tube and experience of the operator on performance of small bowel enema.

Seventy patients underwent small bowel enema (SBE) to assess the influence of experience of the radiologist on the ease of jejunal intubation and the adequacy of SBE using two types of tubes. Comparing intubation time, intubation screening time, total screening time and total room time, we conclude that jejunal intubation is achieved easily, in a reasonable time with both types of tube, by all grades of radiologist, although the experienced operator using the Silk tube achieved intubation in a significantly shorter time. Overall patient acceptability was satisfactory (75%) but was better using the Silk tube, with which entero-gastric reflux and vomiting were less.

Adolescent↗
PubMed1989

Chromosomal abnormalities in fetuses with omphalocele. Significance of omphalocele contents.

Twenty-six consecutive fetuses with a sonographically detectable omphalocele and known karyotype were reviewed to identify risk factors that might be associated with chromosomal abnormalities. Risk factors that were analyzed included contents of the omphalocele sac, maternal age, fetal sex, sonographically detectable concurrent anomalies, and any major concurrent anomaly. Chromosomal abnormalities were found in 10 cases (38%) from trisomy 18 (n = 4), trisomy 13 (n = 4), trisomy 21 (n = 1), or 45, X (n = 1). The absence of liver from the omphalocele sac (intracorporeal liver) was strongly associated with an abnormal karyotype; chromosomal abnormalities were present in all 8 fetuses with an intracorporeal liver compared to 2 of 18 fetuses with an extracorporeal liver (p less than .0001, two-tailed Fisher exact test). Other risk factors that were statistically associated with chromosomal abnormalities included advanced maternal age (greater than or equal to 33 years, p = .03) and sonographically detectable concurrent malformations (p = .05). We conclude that sonographic findings can help determine the relative risk of chromosomal abnormalities in fetuses with omphalocele; abnormal karyotypes were significantly associated with the absence of liver from the omphalocele sac and sonographically detectable concurrent malformations in this series. Sonographers should also be aware that omphaloceles that contain bowel alone tend to be small and can be missed or mistaken for other abdominal wall defects (gastroschisis or umbilical hernia).

Adolescent↗