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Biomedical subjects

P Rogers

Publications and source records attributed to P Rogers.

At least 163 records · Page 9Linked to original sources

Argininosuccinic aciduria: prenatal studies in a family at risk.

We have monitored two successive pregnancies in a family which we found to be at risk for argininosuccinic aciduria. We measured argininosuccinic acid (ASA) concentrations in amniotic fluid and utilized an indirect assay of ASA lyase activity in cultured amniotic fluid cells. The assay procedure is based on the uptake of 14C from [14C]citrulline and of [3H]leucine into protein. ASA was easily measured in amniotic fluid from the first fetus at risk, whereas none was detectable in control fluids. Amniotic fluid cells cultured from this fetus had only 5.5% of control ASA lyase activity. The pregnancy was terminated, and hepatic ASA lyase activity in the fetus was shown to be about 1.3% of control values. In addition, eight fetal tissues were analyzed for ASA, and all had significant accumulation. ASA was not detected in amniotic fluid from the second fetus at risk, and ASA lyase activity in cultured cells was 80% of control activity. Enzymatic analysis of erythrocyte lysate confirmed the diagnosis of an unaffected child (ASA lyase = 46% of control) and indicated heterozygosity. Thus, we provide further evidence that argininosuccinic aciduria can be diagnosed successfully in utero by indirect assay of ASA lyase activity in cultured amniotic fluid cells. In addition, high amniotic fluid ASA concentrations provide strong adjunctive evidence for such a prenatal determination, and may prove to be sufficient for diagnosis.

Adult↗

Crystalline enzyme.substrate complexes of asparate aminotransferase.

Crystalline complexes of cytoplasmic aspartate aminotransferase of pig heart with the substrates L-glutamate and L-aspartate, and with other amino acids, have been prepared and polarized light absorption spectra have been measured. Striking differences in the directions of polarization of the absorption bands are seen. A complete half-transamination of pyridoxal phosphate to pyridoxamine phosphate by aspartate or by cysteine sulfinate can be demonstrated in the crystal as can the accumulation of a quinonoid intermediate with erythro-beta-hydroxyaspartate. X-ray diffraction studies show that the crystals with erythro-beta-hydroxyaspartate and alpha-methylaspartate are isomorphous with those of both alpha and beta subforms of the native enzyme.

Amino Acids↗

Intramitochondrial synthesis of membrane proteins in yeast: differential inhibition by ethidium.

Yeast cells (Saccharomyces cerevisiae) were grown in the presence of [14C]phenylalanine and pulse-labelled with [3H]phenylalanine in the presence of cycloheximide. The proteins extractable into chroloform: methanol (2:1) were isolated from mitochondria and analysed by SDS gel filtration. Four protein fractions varying in molecular weight were separated. In order to identify the transcriptional origin and the site of protein synthesis ethidium bromide was used. Different sensitivity of protein syntheses to various concentrations of ethidium was shown. These data are discussed in relation to the possible presence of two classes of membrane-bound polyribosomes in mitochondria.

Cycloheximide↗

An interdisciplinary clinical training program for dietitians. New primary care function.

One approach to teaching clinical skills to dietetic interns and students has been described. This approach has been taken to promote the use of on-going dietitian-client relationships where appropriate and to help prepare dietitians to function optimally in such situations. It is hoped that other, different programs will emerge with similar goals, the overall impact being one of developing the potential of dietitians as primary health care professionals in their field of expertise.

Clinical Competence↗

Government needs and public expectations.

The priorities for research which emerge from looking at the health needs of patients collectively are examined here. Priorities, however imperfect, are discernible when the five indices of where the main burdens on the health services lie are examined; those indices are inpatient days, outpatient referrals, general practitioner consultations, sickness-benefit days, and loss of life expectancy. Housing, employment, nutrition, etc., are equally relevant to health and to the question of priorities in medical research. It is important in dealing with government needs and public expectations to be clear what health and social services cannot do and what people must do for themselves.

Bed Occupancy↗

Dual regulation by arginine of the expression of the Escherichia coli argECBH operon.

The correlation between the level of messenger ribonucleic acid (mRNA) specific for the argECBH gene cluster (argECBH mRNA) measured by ribonucleic acid-deoxyribonucleic acid (RNA-DNA) hybridization and the rates of synthesis of N-acetylornithine deacetylase (argE enzyme) and of argininosuccinate lyase (argH enzyme) of Escherichia coli strain K-12 were determined for steady-state growth with and without added L-arginine and during the transition periods between these two states. During the transient period after arginine removal (transient derepression), the synthesis of enzymes argE and argH was initially three to five times greater than the steady-state derepressed rate finally reached 50 min later. The level of argECHB mRNA correlated well both quantitatively and temporally with the rates of enzyme synthesis during this transition. The level of in vivo charged arginyl-transfer RNA (tRNAarg), monitored simultaneously, was initially only 5 to 10% and gradually increased to a final level of 80% after 45 min. During the transient period after arginine addition (transient repression), the rates of synthesis of enzymes argE and argH decreased to almost zero and gradually reached steady-state repressed rates after about 180 min. The argECBH mRNA level remained constant at the steady-state repressed level throughout transient repression, revealing a discontinuity between the level of this mRNA and rates of enzyme synthesis. A similar discrepancy was noted during the transition after ornithine addition. In vivo charged tRNAarg remained constant at 80% during this transition. After removal of arginine, the zero-level transient enzyme synthesis developed after only 7.5 min of arginine deprivation and was maximum after 30 min. The results suggest an accumulation of a molecule regulated by arginine that plays a role in transient repression. Our data indicate that arginyl-tRNA synthetase is not this molecule since its synthesis was unaffected by arginine. The ratios of steady-state argE and argH enzyme synthesis without arginine to that with arginine were 12 and 20, respectively, whereas the similar ratio for argECBH mRNA was 2 to 3. The repressed level of argECBH mRNA was not affected by attempts to repress or derepress the ppc+ gene (carried on the DNA used for hybridization), and the repressed level of argECBH mRNA was lowered about 50% in cells carrying an internal argBH deletion. These data taken together indicate the presence of an excess of untranslated argECBH mRNA during both transient and steady-state repression by arginine. Thus, a second regulatory mechanism, not yet defined, appears to play an important role in arginine regulation of enzyme synthesis.

Amidohydrolases↗

Effect of arginine on the stability and size of argECBH messenger ribonucleic acid in Escherichia coli.

The chemical stability of argECBH messenger ribonucleic acid (mRNA) produced by Escherichia coli was found to be unaltered during steady-state repression by arginine. During extreme arginine deprivation, the increase in argECBH mRNA stability was related to general effects of amino acid starvation on mRNA stability. Thus a mechanism whereby argECBH gene expression is regulated by altering the decay rate of this mRNA is not consistent with our data. Sucrose gradient analysis followed by hybridization revealed that both heavy (14S) and light (8S) components of argECBH mRNA were produced by cells of E. coli K-12 grown without arginine, whereas predominantly light (8S) mRNA was produced by cells grown with arginine. A functional argR gene and the EC portion of the argECBH cluster were found essential for the arginine restriction of heavy-mRNA production. Experiments suggest that light argECBH mRNA did not arise from heavy message, and 8u% of both light and heavy mRNA was found bound to ribosomes. The data appear most consistent with the notion that a second site of control by arginine regulates the amounts of light and heavy arginine mRNA in the cell either by early termination of transcription or by endonucleolytic processing. Consideration of these data in conjunction with those of the accompanying report (Krzyzek and Rogers, 1976) permits the tentative conclusion that light argECBH mRNA is not translated into active enzymes and is thus responsible for the discrepancy between the high content of hybridizable mRNA and low rates of enzyme synthesis found during arginine repression.

Amidohydrolases↗

High blood pressure and psychiatric disorder in general practice.

A programme for the control of hypertension has been started in general practice with the principal aim of finding the most effective way of identifying and keeping patients with high blood pressure under continuing control. One objective is to determine the psychiatric state of hypertensive patients in the programme and this paper reports these results.There was no significant difference between the percentage of psychiatric patients in a hypertensive group and a control group. There was no relationship between blood pressure recorded at the initial clinic and the psychiatric state. In both hypertensive and control groups, patients who were on hypertensive treatment at the initial clinic were more likely to be ;psychiatric' than those who were not on treatment; this appears to be less likely to occur if the hypertension is controlled.

Female↗

Validity of clinical examination and mammography as screening tests for breast cancer.

This study is aiming to determine the validity and observer variability of clinical examination and mammography as screening tests for breast cancer. Women over the age of forty are given two independent clinical examinations of the breasts, and mammograms are taken and read independently by two radiologists. This paper presents the results of screening the first 1215 women to be enrolled in the study. At their first screening attendance, 231 women (19%) were referred for surgical opinion, 119 (9-8%) underwent biopsy, and cancer was diagnosed in 17 (1-4%). 2 further cancers were diagnosed in the ensuing six months among women who had been negative on initial screening, representing a false-negative rate of 2 out of 19 (11%). Clinical examination resulted in 189 referrals (15-6%), 90 biopsies (7-4%), and detected 11 cancers; corresponding figures for mammography were 76 referrals (6-3%), 55 biopsies ((4-5%), and 14 cancers. Observer variability was greater for clinical examination than for mammography. These early results suggest that as a screening test mammography compares favourably with clinical examination, but both tests are necessary if many false negatives are to be avoided.

Adult↗

Acceptability of the cytopipette in screening for cervical cancer.

A randomized controlled trial was carried out in which the acceptability of screening for cervical carcinoma in situ by a postal 'do-it-yourself' method--the cytopipette--was compared with that of an invitation to attend a clinic or see a general practitioner for the conventional cervical scrape examination. In parallel with this, a sociological study of women who had been invited by both methods was undertaken in which information was obtained from responders and non-responders on attitudes to health care. The results show that, while the pipette was used by a greater proportion of women overall than the scrape examination, its acceptance by women most at risk of the disease is still not high. It is concluded that, taking into account the relative merits of the two methods as screening tests, as well as their acceptability and cost, the postal pipette may be useful in some circumstances, such as areas where clinical resources are limited, and as a second approach to women who have not taken up the offer of a scrape examination.

Adolescent↗