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Biomedical subjects

G Ryan

Publications and source records attributed to G Ryan.

At least 127 records · Page 7Linked to original sources

Expression of insulin-like growth factor in adult and embryonic kidney.

Insulin-like growth factors (IGFs) I and II are proinsulin-like peptides. IGF I is produced in adult and embryonic kidney. It is likely that IGF I produced locally in adult kidney regulates processes of renal transport, metabolism and growth. Renal IGF I production is stimulated by growth hormone (GH) and by epidermal growth factor (EGF). The identity of additional factors that regulate IGF I gene expression in settings such as compensatory hypertrophy and diabetes mellitus is unknown. IGF I and IGF II produced in embryonic kidney promote the metanephrogenic process. The identity of factors that regulate metanephric IGF gene expression is yet to be determined.

Autoradiography↗

Atrial natriuretic peptide: a vasodilator of the fetoplacental circulation?

Paired maternal and fetal atrial natriuretic peptide concentrations were measured in 62 percutaneous umbilical blood samplings performed principally for the assessment and treatment of rhesus isoimmunization. Pretransfusion fetal atrial natriuretic peptide levels were significantly higher than maternal atrial natriuretic peptide levels (median 117 pg/ml vs median 32 pg/ml; p less than 0.001); paired pretransfusion fetal and maternal atrial natriuretic peptide samples showed a weak correlation with each other (R2 = 17%; p = 0.002). Fetal atrial natriuretic peptide levels correlated inversely with hematocrit (R2 = 14%; p = 0.003), but not with albumin or gestational age. Paired pretransfusion and posttransfusion (median = 134 pg/ml) fetal atrial natriuretic peptide levels (n = 38) showed a significant rise after transfusion (p less than 0.001); this rise was related to the percentage of fetoplacental blood volume transfused (R2 = 33%; p = 0.035). In a subgroup of 26 procedures, change in fetal atrial natriuretic peptide levels was weakly correlated with transient reductions in the Doppler systolic/diastolic ratio of the umbilical artery (R2 = 14%; p = 0.07). These data support work in animals that indicate a role for atrial natriuretic peptide in the human fetus, but these data do not confirm that atrial natriuretic peptide modulates fetoplacental vascular impedance in the human fetus.

Atrial Natriuretic Factor↗

Insulin-like growth factors I and II are produced in the metanephros and are required for growth and development in vitro.

The role(s) of one family of polypeptide growth factors in a developing organ system was examined. Renal anlagen (metanephroi) were surgically removed from 13-d-old rat embryos and grown in organ culture for up to 6 d. Over this period of time when placed in serum-free defined media, the metanephroi increased in size and morphologic complexity. Messenger RNAs for both insulin-like growth factors (IGFs), IGF I and IGF II, were present in the metanephroi. Immunoreactive IGF I and IGF II were produced by the renal anlagen and released into culture media. Levels were relatively constant during the 6 d in culture and averaged 3.5 X 10(-9) M IGF I and 8.3 X 10(-9) M IGF II in media removed from metanephroi after contact for 24 h. IGF binding protein activity was not detected in culture media. Growth and development of metanephroi in vitro was prevented by the addition of anti-IGF I or anti-IGF II antibodies to organ cultures. IGF II produced by metanephroi was active in an IGF II biological assay system and addition of anti-IGF II receptor antibodies to organ cultures prevented growth and development, consistent with the action of IGF II in metanephroi being mediated via the IGF II receptor. The data demonstrate production of both IGF I and IGF II by developing rat metanephroi in organ culture. Each of these peptides is necessary for growth and development of the renal anlage to take place in vitro. Our findings suggest that both IGF I and IGF II are produced within the developing metanephros in vivo and promote renal organogenesis.

Animals↗

Evaluation of two rapid group B streptococcal antigen tests in labor and delivery patients.

Two rapid group B streptococcal antigen tests were compared with nonselective blood agar culture in 1062 unselected patients admitted to labor and delivery. Vaginal specimens taken from each patient on admission were used to perform each of two rapid tests and corresponding cultures. The rapid tests were the Streptex latex agglutination assay and the Equate Strep B test, which uses a solid-phase immunoassay. Overall, 105 patients (9.9%) had at least one positive culture. The sensitivities for the rapid tests were 15.1% for Streptex and 21.5% for Equate. Specificities were 99.3 and 98.7%, respectively. Sensitivity was minimally increased in the setting of ruptured membranes for both tests. Likewise, use of separate swabs for streaking the culture plate and performing the rapid test increased the sensitivity, but this was not significant for either test. In control experiments, the limit of sensitivity of both rapid tests was 5 x 10(6) colony-forming units. We conclude that at present, these tests are not sensitive enough for routine use in this type of clinical setting.

Antigens, Bacterial↗

Risk factors for death in patients admitted to hospital with asthma: a follow-up study.

Hospital records of patients with asthma admitted to teaching hospitals in Perth, Western Australia between 1976 and 1980 were examined retrospectively to identify characteristics of the illness which were associated with subsequent death. From 5722 admissions there were 195 deaths to December 1982, 186 of whom had records available (cases); 452 of the surviving subjects were used for comparison (controls). There was no difference in age of onset of asthma or cigarette smoking habits between the two groups, but ischaemic heart disease as an associated condition was significantly more frequent in cases. On admission to hospital an arterial PCO2 less than 45 mmHg was more frequent in those who died, but there were no differences in arterial PO2, lowest pH, highest or lowest FEV1 and FVC. Cases more frequently used home nebulisers and were more frequently prescribed corticosteroids, antibiotics and sedatives or tranquilizers prior to admission, corticosteroids and sedatives or tranquilisers during admission and sedatives or tranquilisers on discharge. These results suggest that cases had more severe asthma in that they were more often treated with home nebulisers, corticosteroids and antibiotics, but with the exception of PaCO2 the commonly used measurements of severity of asthma did not identify those at risk of death. The prescription of sedatives or tranquillisers appears to be associated with an increased risk of death in subjects with asthma.

Adolescent↗

The effects of nedocromil sodium on the response to grain dust in West Australian grain workers.

Seasonal grain workers in Western Australia who develop respiratory symptoms after exposure to grain dust develop concomitant changes in lung function and bronchial responsiveness to methacholine. The mechanisms underlying these changes are not known. A detailed study was undertaken of seasonal grain workers in Western Australia to evaluate the effect of nedocromil sodium (Fisons, United Kingdom) on these changes to see if they could be prevented by this drug. Forty seven subjects participated. Symptoms and forced expiratory volume in one second (FEV1) were recorded before the study and before, during, and after each working shift, and bronchial responsiveness to methacholine was measured at the beginning and end of the study. Twenty three subjects received nedocromil and 22 received a placebo in a double blind design; there was no difference in baseline characteristics between the two groups. At the end of the study, no differences were found between the nedocromil and placebo groups in the prevalence of symptoms or development of new symptoms during the study. The drug had no effect on changes in methacholine PD20 or FEV1. As in previous studies, new symptoms developing during the season were more common in atopic subjects and were associated with a fall in methacholine PD20. It is concluded that nedocromil has no effect on the development of new symptoms in grain workers. The mechanisms underlying these symptoms require further study.

Adolescent↗

Exposure to grain dust and changes in lung function.

Respiratory symptoms and lung function were assessed in 41 seasonal grain handlers and related to duration of employment and level of exposure to grain dust. Ten public works department employees, not exposed to grain dust, were examined during the same period. Respiratory symptoms, forced expired volume in one second (FEV1), and bronchial responsiveness (dose of methacholine provoking a 20% fall in FEV1-PD20) were assessed before starting work and at weekly intervals during a period of employment lasting up to four weeks. Two atopic grainhandlers with pronounced bronchial hyperresponsiveness (PD20 less than 1 mumol) and a history of asthma withdrew from the study within two weeks because they developed severe asthma. Respiratory symptoms were more frequent and more often attributed to work in the grainhandlers than in the non-exposed subjects. In the grainhandlers the FEV1 decreased by a mean (95% confidence intervals) of 321 ml (198-444) (p less than 0.05) and the mean (95% confidence interval) PD20 decreased from 20.6 mumol (10.3-41.2) to 6.0 mumol (2.8-12.5) (p less than 0.05) after one week of work. Over the next three weeks the mean FEV1 returned towards the prestudy values. The mean PD20, however, remained significantly lower than the initial value. The mean FEV1 and PD20 did not change significantly in the non-exposed subjects. The frequency of symptoms and decreases in FEV1 were greater in grainhandlers when working in jobs where total exposure to dust was greater than 20 mg/m3 than when working in jobs where it was less than 10 mg/m3. The results indicate that occupational exposure to grain dust results in respiratory symptoms and changes in lung function, including increased airway responsiveness, within the first week of exposure to grain dust at work. These changes appear to be determined by the degree of dust exposure and suggest a direct effect of grain dust on the lung in these subjects.

Agricultural Workers' Diseases↗

A monoclonal antibody to bovine brain inositol monophosphatase. Immunoaffinity purification of the brain and kidney enzymes and evidence for their structural identity.

A monoclonal IgG2b(K) antibody, G-2A4, has been generated against bovine brain myo-inositol monophosphatase (EC 3.1.3.25). The identity of the antigen recognized by the antibody was established by using e.l.i.s.a. and Western blotting procedures, and by immunoprecipitation of enzyme activity from crude brain supernatant. In addition, the hydrolysis of Ins1P by crude brain extract was inhibited by up to 83% by the pure antibody. Under identical conditions, the hydrolysis of Ins(1,4)P2 was unaffected. An immunoadsorbent column containing monoclonal antibody G-2A4 covalently attached to CNBr-activated Sepharose 4B has been used for rapid purification of the brain enzyme. Elution conditions have been optimized to allow isolation of the enzyme in high yield (54%) with full retention of column-binding capacity. The enzyme was electrophoretically homogeneous, Mr 30,000 and of higher specific activity than that purified conventionally. Chromatography of the pure enzyme on high resolution ion-exchange columns revealed some charge heterogeneity, possibly indicative of some type of post-translational modification. The immunoadsorbent column has also been used to purify the bovine kidney cortex enzyme to homogeneity. Partial proteolytic fragmentation patterns of the brain and kidney enzymes using endoprotease glu-C were identical, suggesting that they are almost certainly products of the same gene.

Animals↗

Clinical experience with phenytoin prophylaxis in severe preeclampsia.

In North America, magnesium sulfate is the traditional treatment for severe preeclampsia and eclampsia. Its use has been strongly criticized, in that it acts peripherally with no central effect and maternal and neonatal complications are well known. Phenytoin, the mechanism of action of which is clear, seems a logical alternative. Our aim was to develop a safe, practical, effective regimen with the use of phenytoin. In this prospective, descriptive study four dosage regimens were investigated in 104 patients. The initial regimens produced unexpected and unacceptable side effects in comparison with the nonpregnant population. The final regimen (15 mg/kg intravenously, given as 10 mg/kg initially then 5 mg/kg 2 hours later) provided therapeutic levels and had minimal maternal and perinatal side effects. No seizures occurred after its correct usage. This regimen is simple, safe, effective, and provides ongoing anticonvulsant coverage in the postpartum period. We suggest that phenytoin may represent a suitable alternative anticonvulsant in this condition.

Athetosis↗

Coordinate elevations of liver delta-aminolevulinate synthase and cytochrome P-450 RNA by phenobarbital in chicken embryos: the effects of heme.

1. The role of heme in the coordinate elevations of liver delta-aminolevulinate (ALA) synthase activity and microsomal cytochrome P-450 concentration induced by phenobarbital (PB) was investigated in the chicken embryo. 2. Eighteen day old chicken embryos were given PB, and the changes in liver content of PB-inducible cytochrome P-450 RNA and of ALA synthase RNA were determined at different times after exposure to the drug. 3. The concentrations of both types of RNA increased rapidly after PB administration, and by 9 hr the level of ALA synthase RNA was 55-fold higher than control and that of cytochrome P-450 RNA was 7-fold higher than normal. 4. While the rate of increase in ALA synthase activity paralleled closely that of the enzyme's RNA concentration, the rate of increase of spectrally active cytochrome P-450 concentration in microsomes lagged behind that of the apoprotein's RNA by several hours. 5. To test whether heme depletion was responsible for the coordinate inductions of the two enzymes, embryos were loaded with ALA 2 hr before exposure to PB. 6. The protocol led to a drop in the PB-inducible ALA synthase RNA concentration and to an increase in that of cytochrome P-450 RNA, measured 6 hr after drug administration. 7. In primary cultures of hepatocytes, hemin in the culture medium caused a modest drop in ALA synthase RNA concentration but had a variable effect on that of cytochrome P-450 RNA in cells incubated with PB for 9 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Aminolevulinate Synthetase↗

Occupational asthma in a mineral analysis laboratory.

An epidemic of symptoms suggestive of occupational asthma in workers in a mineral analysis laboratory necessitating exposure to vapours of hydrochloric, hydrofluoric, nitric, perchloric, and sulphuric acid solutions was investigated. Variable airflow obstruction was confirmed by serial measurement of FEV1 in two subjects who showed 18% and 22% fall in FEV1 during a workshift. Of a workforce of 21 laboratory staff, 20 took part in a study of ventilatory capacity and bronchial reactivity. All but one subject had normal ventilatory capacity but five had bronchial hyperreactivity (PC20 less than or equal to 8 mg/ml histamine). Four of the five with hyperreactivity had a history of chest tightness at work whereas only two subjects with chest tightness had PC20 greater than 8 mg/ml (p less than 0.01). Other work related symptoms were cough (two subjects) and breathlessness (three subjects). Four of the subjects with bronchial hyperreactivity were atopic, suggesting that hyperreactivity may have predated exposure to irritant material at work and resulted in their being susceptible to the development of symptoms and raises the possibility of identifying susceptible subjects by preplacement examination. In two of these subjects, however, bronchial reactivity has returned to normal after 205 and 376 days away from work, suggesting that bronchial inflammation resulted from occupational exposure to acid vapours.

Acids↗

Bronchial responsiveness, lung mechanics, gas transfer, and corticosteroid response in patients with chronic airflow obstruction.

Thirty patients with stable chronic airflow obstruction receiving regular bronchodilator treatment were studied to determine whether the level of bronchial responsiveness, transfer factor for carbon monoxide (TLCO), or the mechanical properties of the lung predicted a bronchodilator response to oral corticosteroid treatment. Before treatment mean (SD) FEV1 was 48% (16%) of the predicted value (% pred); the geometric mean concentration of methacholine required to produce a 20% fall in FEV1 (PC20) was 0.44 (range 0.07-3.32) mg/ml; and TLCO was 59% (21%) predicted. The exponential constant (k) defining the shape of the static volume-pressure curve was 146% (66%) predicted and pulmonary conductance relative to predicted lung volume at a transpulmonary pressure of 5 cm H2O (sGL5) was 72% (37%) predicted. After prednisolone treatment (0.6 mg kg-1 day-1 for two weeks) FEV1 increased by 8% (19%) (p less than 0.05) and daily mean peak flow (PEF) by 3% (10%) (p less than 0.01) over pretreatment values. Three patients had an increase in FEV1 of more than 30%, two of whom had sputum eosinophilia (p less than 0.05). The three were among the 13 patients with a reduced sGL5. The increase in FEV1 did not correlate with initial PC20 (r = 0.16), k (r = -0.12), or TLCO (r = -0.14). Thus measurements of bronchial responsiveness, lung distensibility, and TLCO did not predict corticosteroid response in patients with stable chronic airflow obstruction. Patients with sputum eosinophilia or reduced pulmonary conductance may be more likely to respond.

Airway Resistance↗

Juvenile sex offenders: development and correction.

This paper addresses the developmental nature of sexually abusive behaviors as they apply to juvenile male sexual offenders. Socialization and sexual victimization are discussed. Three case histories elucidate and support the discussion of the development of victim offending. Significant treatment issues of juvenile male sexual offenders center around the sexual assault cycle which provides a framework for sexual offenders to conceptualize and understand the cognitive, behavioral, psychological, and situational factors which have resulted in their offense(s). Although sexual offenders and sexual offenses are each unique, the sexual assault cycle offers a means of addressing essential commonalities in the treatment of juvenile sexual offenders. Sexual offender specific treatment is viewed as essential for decreasing the risk of further sexual offenses, and thus decreasing the incidence of sexual victimization.

Adolescent↗

A comparison of nonculture-dependent methods for detection of Chlamydia trachomatis infections in pregnant women.

Two nonculture-dependent methods for the detection of Chlamydia trachomatis in endocervical samples from obstetric patients were compared with routine isolation in McCoy cell cultures. When compared with culture, the sensitivities and specificities of the methods were: direct fluorescent antibody staining (MicroTrak [Syva Co.]) 98.1 and 95.4%, and enzyme immunoassay (Chlamydiazyme [Abbott Laboratories]) 96.3 and 92.9%, respectively. In 89% of apparent false-positive direct fluorescent antibody cases and 64% of enzyme immunoassay cases, an additional positive nonculture result was considered to indicate infection missed by culture. Considering these data, revised sensitivities were 84.4% for culture, 95.2% for direct fluorescent antibody, and 95.3% for enzyme immunoassay. Revised specificities were 99.5% for direct fluorescent antibody and 97.3% for enzyme immunoassay. Both nonculture tests appear acceptable for screening high-risk obstetric patients, and may be more sensitive than routine cell culture.

Chlamydia Infections↗

Cystic fibrosis, Crohn's colitis, and adult meconium ileus equivalent.

A 23-year-old man with cystic fibrosis developed massive rectal bleeding that continued intermittently, necessitating an emergency laparotomy and total colectomy. The resected colon was shortened by fibrosis and displayed widespread excessive production of mucus, forming a carpetlike layer over the mucosa as well as segmental discrete areas of mucosal ulceration with fissures, transmural inflammation, and multiple epithelioid granulomas, which are in keeping with Crohn's disease. One case, in a seven-year-old girl, had been reported previously.

Adult↗