Search PubMed⌕ Search

Biomedical subjects

P M Sullivan

Publications and source records attributed to P M Sullivan.

70 records · Page 4Linked to original sources
PubMed1991

Complex structure and regulation of the ABP/SHBG gene.

Extracellular androgen-binding proteins (ABPs) are thought to modulate the regulatory functions of androgens and the trans-acting nuclear androgen receptor. Testicular ABP and plasma sex hormone-binding globulin (SHBG), which is produced in the liver, are encoded by the same gene. We report here that the ABP/SHBG gene is also expressed in fetal rat liver and adult brain. Immunoreactive ABP was localized in the brain and fetal liver and mRNAs were identified in both tissues by northern blot hybridization. Analysis of brain and fetal liver cDNA clones revealed alternatively processed RNAs with sequence characteristics suggesting the encoded proteins could act as competitors of ABP/SHBG binding to cell surface receptors. One cDNA represented a fused transcript of the ABP/SHBG gene and the histidine decarboxylase gene that was apparently formed by a trans-splicing process. Gene sequencing experiments indicate that tissue-specific ABP/SHBG gene promoter-enhancer elements are utilized in testis, brain and fetal liver. These data demonstrate that the structure, RNA transcript processing and likely regulation of the ABP/SHBG gene are very complex.

Androgen-Binding Protein↗
PubMed1991

Retinal blood flow following a tyramine-induced increase in blood pressure.

The effect of increasing systemic blood pressure on retinal blood flow was investigated in anaesthetised miniature pigs. Blood pressure was increased by the infusion of the sympathomimetic amine, tyramine. Volume flow was determined from axial erythrocyte velocity, measured by laser Doppler velocimetry, and vessel diameter, measured from monochromatic retinal photographs. Measurements were taken when mean arterial pressures were elevated by a mean of 22 +/- 3% and 50 +/- 8% above resting values, which represented increases of 31 +/- 2% and 74 +/- 16% in ocular perfusion pressures. Retinal blood flow increased by 8.5 +/- 8% at the lower infusion rate and by 57 +/- 19% at the higher infusion rate. We conclude that tyramine infusion is a suitable method for the study of retinal autoregulation and that the upper limit of retinal autoregulation in miniature pigs lies between 22-50% above resting mean arterial pressure.

Animals↗
PubMed1991

Patterns of physical and sexual abuse of communicatively handicapped children.

Evidence suggests that handicapped children are at increased risk for abuse and neglect. Communicatively impaired youngsters are particularly vulnerable because of their limited ability to report the maltreatment. Of 482 abused handicapped children evaluated at Boys Town National Research Hospital, 212 had hearing impairment, 87 speech language disorders, 39 learning disorders, 43 behavioral-emotional disturbances, 74 mental retardation, 5 visual impairment, 3 cleft lip or palate, and 19 other disorders. The perpetrator was either a relative or a "trusted other" in 97.2% of sexual abuse cases. Handicapped males were much more likely to be victims of sexual abuse than nonhandicapped males in the general population. Children being educated in residential schools were more likely to be sexually abused than mainstreamed youngsters. These children may be at risk for abuse from a wide variety of potential perpetrators, including teachers, dormitory counselors, van drivers, clergy, classroom aides, older students, peer siblings, scout leaders, abused peers, baby-sitters, and custodians.

Adolescent↗
PubMed1991

Effect of meal on retinal blood flow in IDDM patients.

OBJECTIVE: The effect of postprandial hyperglycemia on retinal blood flow was examined in 11 adults with insulin-dependent diabetes mellitus (IDDM) and 9 nondiabetic subjects. RESEARCH DESIGN AND METHODS: Retinal blood flow was measured with bidirectional laser Doppler velocimetry before and 60 and 120 min after a 50-g carbohydrate breakfast. Diabetic subjects were studied twice, being randomized to take their usual insulin (isoglycemic study) or to omit their morning short-acting insulin (hyperglycemic study). Nondiabetic subjects were studied once and received no insulin. RESULTS: Plasma glucose rose significantly (from 11.5 +/- 5.2 to 22.1 +/- 5.5 mM, P less than 0.001) during the hyperglycemic study but not during the isoglycemic or nondiabetic studies. There were no significant changes in blood pressure or retinal blood flow in any of the groups studied. CONCLUSIONS: Short-term hyperglycemia does not increase retinal blood flow.

Blood Glucose↗
PubMed1990

A laser Doppler velocimetry study of the effect of hypoglycaemia on retinal blood flow in the minipig.

The effect of acute hypoglycaemia (plasma glucose less than 2.2 mmol/l) on retinal venous blood flow in the minipig has been determined using bidirectional laser Doppler velocimetry and red free retinal photography. In six pigs the mean flow in a retinal vein increased from 19.3 (+/- 2.8 SEM) microliters/min to 29.7 (+/- 7.5) microliters/min during hypoglycaemia (p less than 0.05) with a return to 18.6 (+/- 3.6) microliters/min when euglycaemia was restored. Retinal blood flow is affected by hypoglycaemia or its haemodynamic consequences.

Animals↗
PubMed1990

Characterization and expression of the complementary DNA encoding rat histidine decarboxylase.

Histamine is a neurotransmitter in the central nervous system and an important modulator of gastric acid secretion, vasomotor control, inflammation, and allergic reactions. In biological systems the formation of histamine from its precursor histidine is catalyzed by the enzyme L-histidine decarboxylase (HDC; L-histidine carboxy-lyase, EC 4.1.1.22). We have cloned HDC-encoding cDNA from a fetal rat liver cDNA library (phage lambda gt11) have deduced the amino acid sequence from the nucleotide sequence. The clone was proven to be HDC cDNA by expression of active recombinant enzyme in COS cells and by chromosomal mapping. The cDNA encodes a protein of Mr 73,450 (655 amino acid residues). The discrepancy between this molecular weight and the size of the purified fetal liver protein subunits [Taguchi, Y., Watanabe, T., Kubota, H., Hayashi, H. & Wada, H. (1984) J. Biol. Chem. 259, 5214-5221] (Mr = 54,000) suggests that HDC may be posttranslationally processed. The 469 amino acid residues from the amino-terminal portion of the protein share 50% identity with rat and Drosophila L-dopa decarboxylases and much less homology with other characterized amino acid decarboxylases.

Amino Acid Sequence↗
PubMed1990

Retinal blood flow during hyperglycemia. A laser Doppler velocimetry study.

The effect of different rates of glucose infusion on the retinal circulation was studied in Gottingen breed minipigs. Seven minipigs were made hyperglycemic rapidly with an intravenous bolus injection of 50% dextrose, after which a slow dextrose infusion maintained hyperglycemia for 60 minutes. Seven minipigs were more gradually made hyperglycemic over 60 minutes with a slow intravenous infusion of 50% dextrose, and a further seven had a control infusion of urea of equal volume and osmolality over 60 minutes. Retinal blood flow (RBF) was determined from the maximum (centerline) velocity of the blood (Vmax) (determined by bidirectional laser doppler velocimetry) and the vessel diameter (D) (determined from monochromatic fundus photographs). Measurements were made in a single temporal retinal vein of each animal at baseline, during, and after each of the infusions. Plasma glucose rose from 6.1 +/- 0.5-25.3 +/- 1.5 mM (mean +/- standard error) during the bolus infusion and from 6.4 +/- 0.7-22.0 +/- 0.7 mM during the slow infusion. The bolus and the slow glucose infusions both produced large increases in RBF (63% and 62%, respectively) which were mainly attributable to increases in Vmax. The urea infusion had no significant effect on RBF, Vmax, or D. The ocular perfusion pressure rose slowly and was significantly elevated after 60 minutes of slow glucose infusion but not after the urea infusion.

Animals↗
PubMed1989

The androgen-binding protein gene is expressed in CD1 mouse testis.

Androgen-binding protein (ABP) is a testicular Sertoli cell secretory protein that acts as a carrier of androgen in the male reproductive tract. ABP has been characterized from a wide range of animal species, including man, rabbit and rat. However, it has been widely accepted that mice do not produce testicular ABP. We have used immunological and molecular biological techniques to demonstrate that the ABP gene is expressed in the CD1 mouse. Steroid-binding, radioimmunoassay and immunocytochemical studies demonstrated that ABP is present in mouse testis and epididymis, but at 1/50 to 1/25 the level of rat epididymis. A 1.7 kilobase mRNA, homologous with rat ABP cDNA, was identified in mouse testis and Sertoli cells by Northern blot hybridization, but at a much lower level than in the rat. An ABP cDNA was isolated from a mouse testis cDNA library and encoded a protein (403 residues) with 89% of the amino acid residues identical to rat ABP, including a signal peptide. Our results indicate that ABP is expressed in the mouse and past failures to detect androgen-binding activity were due to the low level of ABP protein.

Amino Acid Sequence↗
PubMed1988

Cloning of human androgen receptor complementary DNA and localization to the X chromosome.

The androgen receptor (AR) mediates the actions of male sex steroids. Human AR genomic DNA was cloned from a flow-sorted human X chromosome library by using a consensus nucleotide sequence from the DNA-binding domain of the family of nuclear receptors. The AR gene was localized on the human X chromosome between the centromere and q13. Cloned complementary DNA, selected with an AR-specific oligonucleotide probe, was expressed in monkey kidney (COS) cells and yielded a high-affinity androgen-binding protein with steroid-binding specificity corresponding to that of native AR. A predominant messenger RNA species of 9.6 kilobases was identified in human, rat, and mouse tissues known to contain AR and was undetectable in tissues lacking AR androgen-binding activity, including kidney and liver from androgen-insensitive mice. The deduced amino acid sequence of AR within the DNA-binding domain has highest sequence identity with the progesterone receptor.

Amino Acid Sequence↗
PubMed1982

Nonverbal intelligence and English language ability in deaf children.

The relationship between nonverbal intelligence and English language ability in a sample of 25 deaf children between the ages of 6-10 was examined. Intelligence measure included the Performance Scale of the Wechsler Intelligence Scale for Children-Revised (Wechsler, 1974) and the Hiskey-Nebraska Test of Learning Aptitude (Hiskey, 1966). Language measures were the Test of Language Development (Newcomer & Hammill, 1977) and the Reynell Developmental Language Scales (Reynell, 1977). Average correlations of .45 were obtained between nonverbal IQ and the language measures. The average multiple correlation between the individual subtests from the intelligence scales and language scores was .68. Subtests which require visual memory consistently entered the multiple regression equations as the best predictors of language performance. Language performance was attenuated in this sample and did not correlate with chronological age. The finding of significant correlations between nonverbal IQ and English language, in spite of the attenuated language performance, suggests that nonverbal intelligence and visual memory skills, in particular, may be important in understanding the success of some hearing-impaired children in acquiring English and the failure of others.

Child↗
PubMedDate not supplied

Purification and characterization of astrocyte-secreted apolipoprotein E and J-containing lipoproteins from wild-type and human apoE transgenic mice.

The varepsilon4 allele of apolipoprotein E (apoE) is a genetic risk factor for Alzheimer's disease (AD). In order to gain a better understanding of the molecular mechanisms by which apoE and possibly other apolipoproteins produced in the central nervous system (CNS) influence AD pathogenesis, we have purified and characterized the two most abundant apolipoproteins produced in the CNS, apoE and apoJ. We purified apoE and apoJ from primary cultures of mouse astrocytes, which were derived from transgenic mice expressing human apoE isoforms in the absence of mouse apoE. Utilizing antibody affinity columns, we were able to purify both human apoE3 and apoE4, as well as mouse apoJ-containing lipoproteins. Astrocyte-secreted human apoE was present in high density-like lipoproteins of three predominant sizes ranging from 8 to 15 nm in diameter. Mouse apoJ was in particles between 10 and 17 nm in diameter with a peak size range of approximately 11 nm. ApoE and apoJ were in distinct lipoproteins. Utilization of quick-freeze, deep-etch electron microscopy revealed the apoE particles were discs while the apoJ particles were smaller and more irregular in appearance. The lipid composition of apoE particles was very different from those containing apoJ. ApoE-particles contained a similar mass of apoE and lipid, with cholesterol and phospholipid being about equal in mass per particle. ApoJ-particles were relatively lipid poor (three parts protein, one part lipid), with phospholipids being much more abundant than cholesterol. Detailed characterization of phospholipid composition by electrospray ionization mass spectrometry analysis revealed ethanolamine glycerophospholipids to be the most abundant phospholipid present in both apoE and apoJ particles. Analysis of cerebrospinal fluid from apoE3 and apoE4 transgenic mice revealed that human and mouse apoE were in particles the same size as those secreted by astrocytes. Further use of physiological preparations of CNS-derived lipoproteins may allow for a detailed understanding of the role of these molecules in the normal brain and in diseases such as AD.

Animals↗
PubMedDate not supplied

Lead, chromium, and cadmium exposure during abrasive blasting.

An evaluation of lead, cadmium, and chromium exposure was conducted during abrasive blasting of a steel bridge to remove paint in preparation for repainting. Airborne lead concentrations were measured at several locations inside the containment structure, as well as near the workers' breathing zones. Airborne cadmium and chromium were also measured in the containment area. Blood lead levels were monitored in each worker. Airborne lead and cadmium levels in containment exceeded the Occupational Safety and Health Administration's permissible exposure limits by factors of 219 and 3.1, respectively. The use of supplied air-blasting helmets will not effectively reduce workers' lead exposure to the permissible exposure limits when airborne levels are as high as were measured in this study. Studies are needed to evaluate additional engineering controls and alternative paint removal methods. Evaluation of workers' exposure to lead and other hazardous metals is needed for projects involving abrasive blasting. Medical surveillance for cadmium and lead may be necessary for similar projects.

Air Pollutants, Occupational↗