Search PubMed⌕ Search

Biomedical subjects

M Young

Publications and source records attributed to M Young.

At least 127 records · Page 7Linked to original sources
PubMed1997

The three pillars of the new family.

Children are the chief sufferers from the growing fragility of marriages and partnerships. They may also suffer from their mothers going out to paid work unless satisfactory alternative arrangements are made for their care, for instance, by bringing in grandparents to look after their grandchildren when the mothers are not at home. Grandparents may also have an important role when parents separate. There is a dearth of facts about what actually happens. The part played by grandparents has been touched on, but nothing more, in the course of studies in baby care and baby-sitting and the repercussions of the illness of the mother. A Grandparent Commission is proposed to set in motion some of the necessary research and to review official policy as it affects grandparents. If grandparents already do a lot for children, and could do more, a measure of optimism about the future of the family could succeed the prevailing pessimism.

Adult↗
PubMed1997

Evidence of two mechanisms for the activation of the glucose transporter GLUT1 by anisomycin: p38(MAP kinase) activation and protein synthesis inhibition in mammalian cells.

1. Inhibitors of protein synthesis stimulate sugar transport in mammalian cells through activation of plasma membrane GLUT1, the housekeeping isoform of the glucose transporter. However, it has been reported that some of these compounds, in addition to their effect on protein synthesis, also activate protein kinases. 2. In the present study we have explored the role of these two effects on GLUT1 activation. In 3T3-L1 adipocytes and Clone 9 cells, stimulation of sugar transport by puromycin, a translational inhibitor that does not activate kinases, was not detectable until 90 min after exposure. In contrast, stimulation by anisomycin, a potent Jun-NH2-terminal kinase (JNK) agonist, exhibited no lag phase. An intermediate response was observed to emetine and cycloheximide, weak activators of JNK. 3. The potency of anisomycin to stimulate transport acutely (30 min of exposure) was 5- to 10-fold greater than for its chronic stimulation of transport, measured after 4 h of exposure. The stimulation of transport by a low concentration of anisomycin (0.3 microM) was transient, peaked at 30-60 min and it was inhibited (IC50 < 1 microM) by SB203580, which indicates that its mediator is not JNK, but the homologous p38(MAP kinase) (p38(MAPK)). In contrast, the responses to 4 h exposure to 300 microM anisomycin or puromycin were refractory to SB203580. 4. Exposure to anisomycin resulted in rapid activation of p38(MAPK). Activation of both p38(MAPK) and GLUT1 by 0.3 microM anisomycin was cancelled by puromycin. 5. We conclude that the activation of GLUT1 in response to anisomycin includes two components: a delayed component involving translational inhibition and a fast, puromycin-inhibitable component that is secondary to activation of p38(MAPK).

Adipose Tissue↗
PubMed1997

Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle.

GENBANK/dy examines the mechanisms of glucocorticoid-induced insulin resistance in rat soleus muscle. Glucocorticoid excess was induced by administration of dexamethasone to rats for 5 days. Dexamethasone decreased the sensitivity of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation, glycogen synthesis and glucose oxidation to insulin. The total content of GLUT4 glucose transporters was not decreased by dexamethasone; however, the increase in these transporters in the plasma membrane in response to insulin (100 m-units/litre) was lessened. In contrast, the sensitivity of lactate formation to insulin was normal. The content of 2-deoxyglucose in the dexamethasone-treated muscle was decreased at 100 m-units/litre insulin, while the contents of glucose 6-phosphate and fructose 2,6-bisphosphate were normal at all concentrations of insulin studied. The maximal activity of hexokinase in the soleus muscle was not affected by dexamethasone; however, inhibition of this enzyme by glucose 6-phosphate was decreased. These results suggest the following. (1) Glucocorticoid excess causes insulin resistance in skeletal muscle by directly inhibiting the translocation of the GLUT4 glucose transporters to the plasma membrane in response to insulin; since the activity of hexokinase is not affected, the changes in the sensitivity of glucose phosphorylation to insulin seen under these conditions are secondary to those in glucose transport. (2) The sensitivity of glycogen synthesis and glucose oxidation to insulin is decreased, but that of glycolysis is not affected: a redistribution of glucose away from the pathway of glycogen synthesis and glucose oxidation could maintain a normal rate of lactate formation although the rate of glucose transport is decreased.

3-O-Methylglucose↗
PubMed1997

Urethral cultures in female patients with a spinal cord injury.

Quantitative cultures of the urethral meatus were obtained from women with SCI undergoing intermittent catheterization. When compared with the urethral cultures of a group of female subjects, women with SCI had a greater number of isolates of Klebsiella pneumonia and Pseudomonas aeruginosa in the urethral flora. However there was not a significantly greater number of isolates or log numbers of E. coli or Enterococcus sp. in the urethral flora. The E. coli and Enterococcus sp. isolated from the urine were not isolated from the urethra of female patients with SCI in one third of the patients. This poor correlation between the simultaneous urethral and urine cultures of female subjects with SCI may reflect colonization of the urine with organisms that were unable to adhere to the mucosa and colonize the urethra. To what extent these organisms colonize or are temporary residents may be important in the pathogenicity of the infection.

Adult↗
PubMed1997

Glycoprotein changes in tumours: a renaissance in clinical applications.

1. Oligosaccharides linked to protein (glycoprotein) or lipid (glycolipid) are the major components at the outer surface of mammalian cells. Studies using antibodies and lectins have shown in the past that the oligosaccharides they recognize exhibit tumour-associated changes, i.e. they are carbohydrate tumour-associated antigens. 2. The oligosaccharides have been further characterized in recent years by structural analysis using high-resolution chromatographic techniques, MS and NMR. NMR gives an oligosaccharide finger-print that is characteristic of monosaccharide type and linkage and which can be correlated with magnetic resonance spectroscopic data on fine-needle tissue aspirates. 3. Also of relevance is the new understanding of the molecular biology of MUC genes, which code for mucin protein backbones, and of the glycosyltransferase genes, which determine oligosaccharide structure and immunological recognition. 4. For these reasons, we believe that tumour-associated oligosaccharide changes should be revisited in the context of what we now know about structure and expression. This review synopsizes the past data using the detection of carbohydrate tumour-associated antigens by binding of lectins and antibodies, and puts it into the context of NMR fingerprints or signatures.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1997

Conformational properties of the TATA-box binding sequence of DNA.

Nanosecond scale molecular dynamics simulations in water demonstrate that the DNA oligomer, GCGTATATAAAACGC, which contains a target site for the TATA-box binding protein (TBP), has an intrinsic preference to adopt an A-like conformation in the region of the TATA-box and undergoes bending related to that seen within in the TBP complex. This result is obtained from two independent simulations using different starting structures. In line with earlier suggestions of Guzikevich-Guerstein and Shakked, these simulations imply that an A-DNA conformation may be an important intermediate step in forming the strongly distorted DNA observed within the crystallographically determined complex with TBP. These results also support modeling studies by Lebrun et al. which suggest that the TBP binding mechanism can be broken down into a backbone transition to an A-like form coupled with a mechanical distortion which locally stretches and unwinds the DNA.

Binding Sites↗
PubMed1997

Sleep in the laboratory and sleep at home: comparisons of older insomniacs and normal sleepers.

Many laboratory polysomnographic (LPSG) studies have shown only modest sleep differences between insomniacs and matched, noncomplaining normal controls. However, the extent to which LPSG methodology affects the outcome of such comparisons has yet to be tested. In the current investigation, 32 (16 females, 16 males) older (age > or = 60 years) insomniacs and an age-matched and gender-matched sample of 32 noncomplaining normal sleepers underwent three consecutive nights of LPSG monitoring and another three consecutive nights of PSG monitoring in their homes (HPSG). By random assignment, one-half of the subjects in each group underwent LPSG first, whereas the remaining subjects underwent HPSG first. Each PSG recording was blindly scored using conventional scoring criteria, and resulting measures of total sleep period, total sleep time, sleep efficiency percent, stage 1 time, slow-wave sleep time, and rapid eye movement latency were used to compare the two subject groups within each PSG recording site (i.e. lab and home). Statistical analyses showed the normals sleepers and insomniacs evidenced similar pronounced first night effects (FNEs) when undergoing LPSG. However, neither mean values of the selected sleep parameters nor measures reflecting their night-to-night variability differentiated the insomniacs from the normal sleepers when such measures were derived from LPSG. In contrast, FNEs were generally absent for both subject groups when they underwent HPSG. Moreover, the insomniacs displayed significantly greater variability in several of their sleep measures during HPSG than did the normal sleepers. Overall, results suggest FNEs are a concern mainly when using LPSG, and HPSG may be more sensitive than LPSG for documenting sleep differences between normal sleepers and insomniacs. Additional studies are needed to determine if the findings reported herein are similar for young and middle-aged adults.

Aged↗
PubMed1997

Pediatric migraine and the International Headache Society (IHS) criteria.

BACKGROUND: The optimal criteria for the diagnosis of migraine without aura in children are controversial. One strategy for assessing the validity of diagnostic criteria is to compare them with expert clinical diagnoses. OBJECTIVE: To study the agreement between clinical headache diagnoses assigned by pediatric neurologists and symptom-based diagnoses using the International Headache Society (IHS) criteria as well as alternative case definitions. METHODS: We reviewed the records of 253 children and adolescents consecutively evaluated by pediatric neurologists at the Montefiore Headache Unit. Clinical diagnoses assigned by the physicians were used as the gold standard in evaluating the validity of the IHS criteria for the diagnosis of migraine without aura. Alternative symptom-based diagnoses were compared with the clinical gold standard. RESULTS: Detailed headache histories were abstracted from charts of 253 children; 167 children had complete data on all features required for IHS diagnosis. Eighty-eight (52.7%) children received a diagnosis of migraine without aura. Using the clinical diagnosis as the gold standard, the IHS criteria had a sensitivity of 27.3% and a specificity of 92.4%. The poor sensitivity of the IHS definition is a consequence of the rarity of certain features in children clinically diagnosed with migraine: duration of 2 hours or longer (55.7%), unilateral pain (34.1%), vomiting (47.7%), and phonophobia (27.3%). Based on these findings we suggested a definition for pediatric migraine headache without aura that is less complex, more sensitive (71.6%), and almost as specific as the IHS criteria. CONCLUSIONS: The IHS criteria for migraine without aura have poor sensitivity but high specificity using a clinical diagnosis as the gold standard. The IHS criteria should be modified to better reflect current pediatric clinical practice.

Adolescent↗
PubMed1997

Evaluation of selected life-skill modules from the contemporary health series with students in grade.

The purpose of the study was to assess the effects over a school term of selected life-skill modules from The Contemporary Health Series-Into Adolescence on scores for self-esteem, health (drug) attitudes, and behaviors of sixth-grade students. The 328 students were from classrooms assigned to either-experimental or control conditions. Analysis indicated that students exposed to selected modules from the curriculum series reported positive changes on a number of health-related variables in the questionnaire.

Adolescent↗
PubMed1997

Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene.

Although the molecular defect in patients in a Japanese family with mild to moderately severe hemophilia A was a deletion of a single nucleotide T within an A8TA2 sequence of exon 14 of the factor VIII gene, the severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient's plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulting in restoration of the reading frame and/or (ii) "ribosomal frameshifting" resulting in the production of normal factor VIII polypeptide and, thus, in a milder than expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A10 instead of A8TA2, after the delT. Errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype.

DNA Replication↗
PubMed1997

Problems affecting Asian women with diabetes.

Diabetes is common among British Asians, who require appropriate advice and information. Cultural and language difficulties may create a barrier to information. A sensitive, knowledgeable approach and the use of information leaflets and videos in appropriate languages can help overcome this barrier.

Asia↗
PubMed1997

Mineralocorticoid receptors, salt, and hypertension.

This review, covering work from the Baker Institute and elsewhere, is divided into four sections. In the first a summary account of two areas-mineralocorticoid receptors and the enzyme 11 beta hyderoxysteroid dehydrogenase-will be given as background. Next is a brief consideration of the three single-gene causes of human hypertension described to date-glucocorticoid-remediable aldosteronism. Liddle's syndrome, and apparent mineralocorticoid excess-in all of which abnormal sodium handling is a feature. Third, the sequelae of aldosterone occupancy of nonepithelial mineralocorticoid receptors will be analyzed in some detail by reviewing studies on experimental mineralocorticoid hypertension and cardiac fibrosis from this laboratory and elsewhere. Finally, three recent studies from this laboratory will be presented: on putative 11-ketosteroid receptors in epithelial tissue, on glucose-PKC potentiation of mineralocorticoid effects on heart cells, and on the necessity for factors/ processes other than the conversion of cortisol to cortisone (or, in the rat, corticosterone to 11-dehydrocorticosterone) to ensure aldosterone-specific effects in mineralocorticoid target tissues.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Intravenous immunoglobulin in symptomatic and asymptomatic children with perinatal HIV infection.

One hundred thirty-five children born to human immunodeficiency virus (HIV)-infected mothers were selected randomly to receive immunoglobulin (Gamimune-N, Miles Pharmaceutical Co) 200 mg/kg monthly for 1 year. All patients were seropositive by ELISA and Western blot at birth. At the time of the study, 15 symptomatic (P2) and 57 asymptomatic (P1) patients with evidence of viral infection (positive HIV culture or P24 antigen) received the immunoglobulin. Sixty-three indeterminate (PO) patients with no evidence of infection served as the control. Mean age for infants in group P2 was 32 months, 26 months for group P1, and 11 months for group PO. Significant reduction in the frequency of bacterial infections (ie, otitis media, upper respiratory tract infections, urinary tract infections, and acute gastroenteritis) was seen in the symptomatic group compared with both the asymptomatic and the control groups. Growth as measured by weight and height > 50th percentile was also markedly better in the symptomatic group than either asymptomatic or control patients. There was no significant difference in head circumference in all three groups. These results indicate that monthly intravenous immunoglobulin infusion (IVIG) appears to be beneficial to both symptomatic and asymptomatic HIV patients in reducing the frequency of bacterial infection and also enhancement of the immune response. However, symptomatic patients responded much better than the asymptomatic patients.

CD4 Lymphocyte Count↗
PubMed1997

Definition of the elements required for the activity of the rat aromatase promoter in steroidogenic cell lines.

The rate limiting step in estrogen biosynthesis is catalysed by an enzyme complex that includes the aromatase cytochrome P450 (CYP19), and regulation of the synthesis of this steroidogenic P450 is the level at which estrogen synthesis is controlled. In the rat, initiation of aromatase mRNA transcription occurs immediately 5' to the initiator methionine (proximal promoter) in the rat ovary and in two rat Leydig tumor cell lines that express high levels of aromatase (R2C and H540). Although the same site of transcription initiation is employed in both the Leydig tumor cells and in granulosa cells, the patterns of aromatase expression are distinctive. To define the mechanisms controlling aromatase expression in these model cell lines, we have studied the proximal promoter of the rat aromatase using transfection and gel mobility shift assays. These experiments indicate that the SF-1 motif is required for the expression of the reporter gene in each steroidogenic cell line, and that different combinations of CRE-like elements (particularly those located at -169 and -231) are required for full promoter activity in each steroidogenic cell line. In keeping with the results of the functional assays, we were able to demonstrate the binding of nuclear proteins from each of the Leydig tumor cells to the SF-1 motif in mobility shift assays. Nuclear proteins which bind to the CRE-like elements at -169 and -231 were detected in each of the steroidogenic cell lines, but different complexes were observed using extracts from the Leydig tumor cell lines compared to those visualized using extracts prepared from Y1 cells, an adrenocortical tumor cell line that expresses low levels of aromatase activity. Our findings suggest that, in these model steroidogenic cell lines, differences in the proteins that bind to different combinations of elements within the rat aromatase promoter are responsible for the different patterns and levels of aromatase expression which are observed.

Animals↗
PubMed1997

Do our methods lead to insomniacs' madness?: Daytime testing after laboratory and home-based polysomnographic studies.

Complaints of daytime dysfunction are common among chronic insomniacs, but laboratory comparisons of insomniacs and age-matched and gender-matched normal controls have generally failed to document these complaints. However, a few studies, which allowed subjects to sleep in their homes on the nights before daytime testing, have shown some relative diurnal deficits among insomniacs. The current study compared the effects of nocturnal laboratory and home polysomnogram (PSG) studies on subsequent daytime test results among older insomniacs and normal sleepers. Insomniacs (n = 32) and normal sleepers (n = 32) were randomly assigned to first undergo three nights of nocturnal PSG monitoring either in the sleep laboratory (16 insomniacs, 16 normal sleepers) or in their homes (16 insomniacs, 16 normal sleepers). Following the third night of PSG monitoring, subjects spent 1 day in the sleep laboratory, where they completed a four-trial multiple sleep latency test along with four trials of a computer-administered performance test battery. Results showed that insomniacs, as a group, were slightly, albeit consistently, sleepier than were normal sleepers following nights of home sleep monitoring, but a reverse of this trend was found among subjects who underwent nocturnal laboratory PSG before daytime testing. Furthermore, normal sleepers showed faster reaction times on a signal detection task than did insomniacs within the subgroup who underwent home PSGs prior to such testing. However, within the subgroup that underwent nocturnal laboratory PSGs, insomniacs' signal detection reaction times were significantly faster than those shown by normal sleepers. Results provide some support for the speculation that the nocturnal PSG monitoring site, used as a precursor to daytime testing, may systematically affect daytime comparisons between insomniacs and matched controls. Moreover, these results suggest that the use of home-based nocturnal PSG monitoring prior to daytime testing may provide an enhanced understanding of insomniacs' diurnal complaints.

Aged↗
PubMed1997

Angiogenic protein expression in advanced epithelial ovarian cancer.

We set out to determine whether advanced epithelial ovarian cancer (EOC) is associated with elevated serum and ascitic concentrations of the angiogenic factors angiogenin (ANG), basic fibroblastic growth factor (bFGF), and vascular endothelial growth factor (VEGF), and whether the expression of angiogenic factors was associated with tumor vascularity. Serum and ascitic samples were collected from previously untreated patients with FIGO stage III and IV EOC and stored at -70 degreesC. Levels of the three factors were determined by enzyme-linked immunoassay. Histological sections from paraffin blocks of ovarian cancers were stained immunochemically for factor VIII, CD34, and VEGF. Thirty-nine patients were studied, although not all had paired serum and ascitic samples. For each angiogenic factor, the following findings were noted: (a) there was a wide range in serum and ascitic fluid concentrations; (b) the mean serum concentration was higher (P < 0.05) than the mean concentration in normal serum; and (c) the mean serum concentration was lower (P < 0. 05) than the mean ascitic concentration. Overall, the most consistent pattern of elevated serum and ascitic concentrations was with bFGF. With serum samples, 38.9% of patients had a normal VEGF concentration, as did 15.3% for ANG and 7.7% for bFGF. In ascites, the VEGF concentration was in the range for normal serum in 24.5% of samples, compared to 39.4% for ANG and 2.8% for bFGF. In paired samples, both VEGF and bFGF showed higher ascitic concentrations in 100 and 88.3% of samples, compared to 53.3% for ANG. There was no correlation between the serum and/or ascitic concentration of one factor and that of another, suggesting that these factors are independently regulated. Staining with anti-CD34 was more sensitive and reliable than with anti-factor VIII. VEGF staining was most prominent in poorly differentiated tumors and was observed only on tumor cells. There was no correlation between the serum or ascitic concentrations of angiogenic factors and tumor vascularity. Advanced EOC is associated with raised serum and ascitic bFGF concentrations and with markedly elevated ascitic VEGF in most cases. Serum VEGF and serum and ascitic ANG are less often elevated. There was no correlation between the angiogenic profile in serum and ascites and tumor vascularity.

Antigens, CD34↗