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D J Hall

Publications and source records attributed to D J Hall.

At least 91 records · Page 5Linked to original sources
PubMed1989

Evidence for a novel signal transduction pathway activated by platelet-derived growth factor and by double-stranded RNA.

Platelet-derived growth factor (PDGF) and the synthetic double-stranded RNA poly(I).poly(C) [poly(I.C)] stimulate transcription of the JE gene in BALB/c-3T3 fibroblasts. The response of JE to poly(I.C) does not appear to be channeled through any known component of the PDGF receptor signal transduction apparatus. In addition, JE sequences upstream of the transcription start site are devoid of previously identified poly(I.C)-responsive elements, such as those found in the beta-interferon gene. These data suggest that a novel signal transduction pathway regulates the JE response to PDGF and double-stranded RNA. The c-myc and c-fos proto-oncogenes also respond to this pathway but with poor efficiency. However, this pathway operates very efficiently on other PDGF-inducible genes that encode the secretory proteins KC and M-CSF.

1-Phosphatidylinositol 4-Kinase↗
PubMed1989

Labile repressors are involved in the transcriptional control of PDGF-responsive genes.

Platelet-derived growth factor (PDGF) stimulates the transcription of a number of genes in BALB/c-3T3 fibroblasts. Some of these genes (notably the c-myc and c-fo proto-oncogenes) are induced also by phorbol-based tumor promoters which activate protein kinase C. It appears that the response of these genes to PDGF is actually channeled through the activation of protein kinase C. However, other PDGF-inducible genes such as JE, KC, and JB do not respond to tumor promoter. Data suggest that a labile repressor protein blocks the transcriptional response of these genes to tumor promoter. This labile repressor is specific for elements in the JE, KC, and JB genes for it has no effect on the activation of the SV40 early promoter, which is a known target for phorbol ester-inducible transativation.

Animals↗
PubMed1988

Platelet-derived growth factor generates at least two distinct intracellular signals that modulate gene expression.

Regulation of the genes by PDGF has some common features. All are primary response genes, and they can still be expressed in the presence of cycloheximide (Cochran et al. 1983; Kelly et al. 1983; Kruijer et al. 1984; Lau and Nathans 1985). In fact, many of the genes are superinduced when cells are treated with growth factors plus cycloheximide (Greenberg et al. 1986). The genes that have been characterized all contain a sequence motif in their 3'-noncoding sequences that appears to make the message labile (Meijlink et al. 1985; Treisman 1985; Shaw and Kamen 1986). All competence genes so far examined are controlled at least in part at the level of transcription (Cochran et al. 1983; Edwards et al. 1985; Almendral et al. 1988). Differences in regulation of the genes include variations in the time course of induction, ranging from 10 minutes to over 4 hours, and differences in the persistence of the mRNAs after their synthesis (Cochran et al. 1983; Muller et al. 1984; Lau and Nathans 1987). The data presented in this paper strongly suggest that multiple, distinct intracellular signals that lead to the expression of multiple genes are generated when cells are treated with growth factors such as PDGF. The variation in the time course of induction of PDGF-inducible genes suggests several models of signal transduction. Four such models are presented in Figure 5. One possibility (Fig. 5A) is that one signal is generated by the interaction of PDGF with its receptor and that this signal activates the very early genes, such as c-fos.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Platelet-derived growth factor-inducible genes respond differentially to at least two distinct intracellular second messengers.

Platelet-derived growth factor (PDGF) stimulates expression of the c-myc, c-fos, JE, and KC genes in BALB/c/3T3 cells. Here we show that these genes respond differentially to at least two distinct intracellular second messengers generated by PDGF. A broad body of data support the view that response of the c-myc and c-fos genes to PDGF is channeled, at least in part, through activation of protein kinase C. Both PDGF and protein kinase C agonists stimulate transcription of c-myc and c-fos. Down regulation of protein kinase C inhibits the transcriptional induction of c-fos and c-myc by PDGF. In contrast, protein kinase C agonists do not stimulate transcription of JE and KC. Down regulation of protein kinase C does not inhibit the ability of PDGF to stimulate transcription of JE and KC. The differential response of these four genes to PDGF and 12-O-tetradecanoylphorbol-13-acetate correlates with differential phosphorylation of specific intracellular proteins. PDGF treatment stimulates phosphorylation of intracellular proteins at 31, 32, and 80 kilodaltons. Down regulation of protein kinase C prevents phosphorylation of the 80-kDa protein in response to PDGF, but phosphorylation of the smaller proteins is not affected. Finally, PDGF which induces all four genes (and stimulates phosphorylation of three proteins) is a much more potent mitogen than protein kinase C agonists which regulate only some of these events.

Animals↗
PubMed1987

Iatrogenic superior vena cava syndrome treated with streptokinase.

The development of an iatrogenic superior vena cava syndrome secondary to a thrombosis from an indwelling Hickman catheter in a patient with ovarian carcinoma is presented. The patient was treated with a combination of streptokinase and heparin with successful and dramatic results. Streptokinase appears to be highly effective in the treatment of iatrogenic superior vena cava syndrome from Hickman catheters. It appears that the Hickman catheter may be safely left in situ post-treatment.

Catheterization↗
PubMed1986

Parental involvement in the lives of children in hospital.

A care by parent scheme was established in the children's department of a university hospital. It was seen as the natural extension of the increased involvement of parents in the care of their children in hospital. A structured observational study was carried out to monitor its effect on the lives of child patients. Children in the scheme spent far less time awake alone, cried less, and slept less than those nursed unaccompanied. They had far more social interaction with a smaller number of adults, most of their contacts being with family members rather than hospital staff. Children with a resident parent but outside the scheme were generally in an intermediate position on these factors.

Adult↗
PubMed1986

The metabolism of nicardipine hydrochloride in healthy male volunteers.

Four human volunteers given a 30 mg oral dose of nicardipine hydrochloride containing 40 microCi of the 14C-labelled material achieved peak plasma levels of compound-related radioactivity within one hour of dosing. Parent compound comprised only a minor fraction of the circulating radioactivity indicating rapid first-pass metabolism. Plasma radioactivity declined to background levels within 96 h and was excreted both in the urine and faeces. Urinary excretion was the favoured route comprising about 60% of the dosed radioactivity. Mean total recovered radioactivity amounted to 94.8%. Both 1,4-dihydropyridine and pyridine metabolites of nicardipine hydrochloride were excreted in the urine. The major urinary metabolites, comprising some 36% of the radioactivity excreted in the 0-8 h post-dose period, were the glucuronide conjugates of +/- 2-hydroxyethyl methyl-1,4-dihydro-2,6-dimethyl-4(m-nitrophenyl)-3,5-pyridine dicarboxylate and its pyridine from 2-hydroxyethyl methyl-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridine dicarboxylate.

Adult↗
PubMed1986

Genetic aspects of Perthes' disease. A critical review.

Contradictory theories of the mode of inheritance of Perthes' disease have been largely due to sampling error, which is revealed by comparison of four series. Confusion also has been caused by the unequal sex incidence of the disease. Family data from a series of 87 boys and 58 girls with Perthes' disease were combined with those of Gray et al. (223 boys and 44 girls) to provide the largest possible group for analysis. Proportions of first-, second-, and third-degree relatives affected were recorded separately for each sex of index cases and each sex of relatives. Comparison of the incidence of Perthes' disease in relatives with that in the general population of the same sex revealed features of multifactorial inheritance, and a gradient of 35:4:4:1 from first:second:third-degree relatives to the general population. Equal estimates of heritability (h2) from first cousin and sib data suggest that environmental factors are of relatively little importance in etiology. Heritability from sib data was 84 +/- 4%, giving a recurrence risk of 2.6% for sibs and offspring, which agrees with the empirical figure of 2.4%. It is argued that the concentration of cases in certain families is not inconsistent with multifactorial inheritance.

Female↗
PubMed1986

A longitudinal study of carpal bone development in Perthes' disease: its significance for both radiologic standstill and bilateral disease.

This paper reports a longitudinal study of carpal bone development in 125 children (98 boys, 27 girls) attending a clinic for Perthes' disease. The age at appearance of ossification in each carpal bone was estimated by studying consecutive radiographs obtained at six-months intervals. The results were compared with the findings for normal children published by Stuart et al. Three radiologic groups of carpal bone maturation are defined: not delayed (capitate and hamate); markedly delayed (triquetral and lunate); and slightly delayed (scaphoid, trapezium, and trapezoid). Overall, the bone age delay is severely abnormal at three to five years of chronologic age and indicates the time in development when general abnormalities occur. The mean age at diagnosis (and standard deviation) for 34 boys with skeletal standstill was 4.49 +/- 1.07 years, compared with 7.28 +/- 2.40 years for 51 boys without such standstill; the mean age at appearance of carpal bones was not significantly different between these two groups, suggesting an equally profound delay of carpal maturation in the group of later-diagnosed boys. Boys with bilateral hip disease show a significant delay in age at ossification of the trapezoid compared with boys who have unilateral disease. The immaturity of bone age may be present during a latent period and be of etiologic significance in the onset of the hip disease, but at present the evidence links it only with bilateral disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Carpal Bones↗
PubMed1986

An assessment of endocrine function in boys with Perthes' disease.

The frequent association of short stature and retardation of skeletal maturation in Perthes' disease has prompted an investigation of growth-related hormones in this condition. A group of 18 prepubertal boys, aged five to 11 years, who either had a bone age two years or more less than their chronologic age or whose heights were less than the third centile, were studied. Their serum growth hormone (Se GH) response to insulin-induced hypoglycemia was significantly reduced, compared with a control group of short boys. They also demonstrated a tendency to elevated levels of somatomedin activity, measured by chick cartilage bioassay. Thyroid function was normal. These findings suggest a defect in the pituitary-somatomedin-target tissue axis in Perthes' disease.

Child↗
PubMed1986

Raised somatomedin activity in the serum of young boys with Perthes' disease revealed by bioassay. A disease of growth transition?

This paper reports a study of the serum somatomedin activity in 67 boys with Perthes' disease and in 43 control boys aged three to 11 years. It was undertaken to evaluate some abnormalities of growth in children with Perthes' disease that have been previously reported. A brief account is given of knowledge relating to somatomedins in postnatal and fetal life. Serum somatomedin activity was measured using a bioassay based on the principle that somatomedins stimulate the synthesis of both DNA and proteoglycans in porcine costal cartilage. In control boys, the serum somatomedin activity increased with age, which is consistent with previous reports for normal children. In affected boys, the normal increase in serum somatomedin activity with age did not occur. The somatomedin activity in affected boys is higher than in control boys at three to five years but not at six to 11 years of age. Findings support the hypothesis that some children with Perthes' disease have an abnormality of the growth hormone-dependent somatomedins. The serum findings together with those of both skeletal age delay and impaired skeletal growth distally in the limbs are consistent with the view that the general disorder of some children with Perthes' disease results from an imbalance in mechanisms that determine the postnatal transition from the "fetal" to the "basic" component of the normal human growth curve.

Bone Diseases, Developmental↗
PubMed1985

The metabolism and pharmacokinetics of nicardipine hydrochloride in man.

Studies have been carried out to investigate the disposition of nicardipine hydrochloride following intravenous and oral administration to male volunteers. Following oral administration of a radiolabelled dose, nicardipine was shown to be rapidly and extensively metabolised and to be rapidly eliminated from plasma. After intravenous infusion of nicardipine at 5 mg-1 for 3 h, plasma levels declined biexponentially, and clearance values were of the same order as hepatic blood flow. With repeated oral administration, 20 mg three times daily for 28 days, plasma levels rose over the first 3 days of administration and then declined to some extent. Possible reasons for this decline are discussed. Steady-state plasma levels and bioavailability show a nonlinear relationship with doses over the range 10-40 mg three times daily. Food consumption has been shown to reduce the bioavailability of nicardipine when the food is taken before or at the same time as nicardipine administration.

Administration, Oral↗
PubMed1985

Breast feeding: differences in prevalence between caucasian and negroid women resident in Paddington and North Kensington, London, England.

Three hundred and thirty-seven caucasian women and 150 negroid women who were resident in an inner London health district, who gave birth in the district's maternity unit and who were transferred home before 6 days after delivery were studied in respect of their intentions and practices for feeding their babies. Differences in the numbers breast feeding within and between various sub-groups of the two racial groups were compared and inferences drawn in respect of to which group effort in promoting breast feeding should be directed.

Adult↗
PubMed1984

First year of an inner city general practitioner community hospital.

The first inner city general practitioner community hospital opened on 4 January 1982. This paper describes the operation of the hospital over the first 12 months. There were 316 admissions, with an average length of stay of 13 days. The average age of the patients was 73 and the most common reason for admission was disease of the respiratory system. Thirty five per cent of patients were admitted because of an acute illness and 37% were admitted on the same day as the request for admission. The policies of intermittent or phased care allowed for the admission of patients at regular intervals to relieve carers, and the assessment of the home circumstances of all patients allowed for planning the patient's return home.

Acute Disease↗
PubMed1984

Effects of temperature on aggregation and the mitogen-induced exit of lymphocytes from the resting state.

We have determined the temperature dependence of the kinetics of entry into the first S phase of phytohemagglutinin-stimulated lymphocytes under conditions varying the stability of substrata over which the cells have settled. An exponential model was used to characterize entry into S phase. This model yields as parameters duration of lag period, t0, apparent first order rate constant for entry, k, and the number of cells committed to enter the first S phase, NA(t0). Values of t0 and NA(t0) show a 1.5-fold and 2.0-fold decrease and increase, respectively, over a 4 degrees C temperature range and are independent of variation in substrate stability. The temperature dependence of the apparent first-order rate constant, k, however, is strongly influenced by stability. The observed activation energy increases from 3.0 kcal to 37 kcal when the substratum is agitated. This correlates well with reduced adherence of multicellular aggregates in agitated samples. The temperature dependencies for these three parameters are all numerically different, indicating that these parameters are determined by different rate-limiting processes. We propose that the mechanism mirrored by k is linked to the adherence of multicellular aggregates to the substratum.

Cell Aggregation↗
PubMed1984

Alterations in nasal airway resistance following superior repositioning of the maxilla.

Superior repositioning of the maxilla is a contemporary surgical procedure used to correct a variety of dentofacial deformities, including vertical maxillary excess. Concern for the effect of this procedure on nasal respiration is warranted, since superior repositioning of the maxilla may decrease the volume of the nasal cavity. In this study pre- and postoperative nasal-resistance values were obtained for 52 patients who underwent superior repositioning of the maxilla by the LeFort I downfracture procedure. Of these 52 patients, 24 underwent segmental osteotomies and 28 underwent one-piece superior repositioning. Results indicate that the long-faced persons for whom superior repositioning of the maxilla is recommended usually have pretreatment nasal-resistance values within previously reported normal ranges. Superior repositioning of the maxilla, with or without involvement of the nasal floor, usually results in decreased nasal resistance.

Adolescent↗