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Biomedical subjects

M M Roberts

Publications and source records attributed to M M Roberts.

At least 37 records · Page 2Linked to original sources
PubMed1994

Control of posterior pituitary vasopressin content: implications for the regulation of the vasopressin gene.

Axon terminals in the posterior pituitary store large quantities of the hormone vasopressin (AVP), buffering the synthesizing neurons in the hypothalamus against acute changes in physiological demand for hormone release. The dynamics of pituitary AVP content reflect the competing processes of release and synthesis. This report demonstrates substantial increases in pituitary AVP content in the maturing rat. Between 7-10 weeks of age, the total pituitary AVP content in the rat increases from 957 +/- 72 to 1667 +/- 160 ng. Cross-sectional data indicate a parallel relationship between body weight and pituitary AVP content. Nevertheless, weight maintenance does not affect age-related increases in AVP content. Decreasing demand for hormone release and synthesis by inducing hyponatremia blocks subsequent pituitary accumulation. After withdrawing the hyponatremic experimental conditions, animals resume accumulation of pituitary AVP, but do not catch up to age-matched controls. This indicates that increases in pituitary AVP content do not result from a feedback signal from the neural lobe, but rather, pituitary AVP levels passively reflect changes in hormone release and compensatory synthesis.

Aging↗
PubMed1993

c-fos expression in vasopressin and oxytocin neurons reveals functional heterogeneity within magnocellular neurons.

The c-fos protein is rapidly induced in hypothalamic magnocellular nuclei following hemorrhage. We used specific antibodies directed against c-fos and either vasopressin (AVP) or oxytocin (OT) neurophysin to investigate c-fos activation in individual AVP and OT neurons. AVP and OT neurons expressed c-fos in response to hypovolemic stimuli. Following a protocol of incremental hemorrhage, AVP and OT neurons expressed c-fos with a graded response that correlated with stimulus intensity. As the volume of hemorrhage increased, there was an increase in the number of cells expressing c-fos as well as in the amount of c-fos immunoreactivity per cell. These increases correlated with the amount of hormone released into the peripheral blood. In addition, a differential pattern of activation for AVP neurons occurred in response to hemorrhagic stimuli. AVP neurons in the supraoptic nucleus (SON) had a lower threshold for response than those in the paraventricular nucleus (PVN). For OT, activation required a greater blood loss than AVP and c-fos expression encompassed both SON and PVN neurons. We conclude that c-fos expression is proportional to stimulus intensity and reveals functional heterogeneity among magnocellular neurons.

Animals↗
PubMed1993

Immune reconstitution following peripheral blood stem cell transplantation, autologous bone marrow transplantation and allogeneic bone marrow transplantation.

The rate and pattern of recovery of total lymphocytes, T cell subsets, B cells and NK cells were compared for 12 months following recovery phase peripheral blood stem cell (PBSC) autotransplantation (n = 49), autologous (n = 7) and allogeneic BMT (n = 11). The PBSC group had a significantly faster recovery of total lymphocyte count, total T cells (CD3+ cells), CD8 cells and CD4 cells than the allogeneic BMT group. The pattern of earlier recovery of CD8 cells than CD4 cells was the same for each type of transplant. Reconstitution following autologous BMT was intermediate between PBSC and allogeneic BMT. Multivariate analysis identified type of transplant, number of mononuclear cells transplanted and conditioning regimen as significantly influencing immune recovery.

B-Lymphocyte Subsets↗
PubMed1992

Assessment of non-palpable mammographic abnormalities: comparison between screening and symptomatic clinics.

A retrospective study found that a breast screening clinic generated fewer localization biopsies for non-palpable mammographic abnormalities than a symptomatic clinic (3.36 versus 9.89 per 1000 mammograms, respectively) and that a greater proportion of such biopsies were malignant. This study determined the reason for this difference. There were 108 of 304 (35.5 per cent) and 17 of 130 (13.1 per cent) carcinomas in women attending the screening and breast clinics respectively (relative risk 2.72 (95 per cent confidence interval 1.70-4.34)). This difference was regardless of age. The characteristics of the mammographic abnormality, the Wolfe pattern, a family history of breast carcinoma, parity and age at first pregnancy were similar in both groups. Women attending the screening clinic were referred for localization biopsy after assessment by clinicians and radiologists at a joint clinic; there was no joint assessment for patients attending the breast clinic. The same staff attended both clinics, although the proportion of time spent at each varied. This study suggests that all women with a non-palpable mammographic abnormality should be reviewed at a joint assessment clinic before localization biopsy is recommended.

Biopsy↗
PubMed1992

Models of neurohypophyseal homeostasis.

Rats subject to prolonged (3-6 days) hypernatremia show significantly decreased pituitary vasopressin content as well as increased levels of hypothalamic vasopressin mRNA; these values return to baseline levels after the stimulus is removed. In this paper, we tested whether a single cellular mechanism for regulation of synthesis could account for the experimental observations of both pituitary hormone depletion-repletion and hypothalamic mRNA content. We developed several "minimal" models of vasopressin synthesis in which control of hormone synthesis was regulated exclusively by transcription, translation, or mRNA decay and tested each model to see which best emulated the dynamics of neuro-hypophyseal vasopressin content and hypothalamic vasopressin mRNA. Experimental data provided parameters for pituitary content, baseline and stimulated release rates, mRNA decay, transcription, and translation. Models based exclusively on translation and mRNA decay failed to produce predictions similar to experimental observations. Of the models tested, the transcription model provided predictions most consistent with laboratory data, although some quantitative differences remain. The results of the computer modeling strongly suggest that transcription represents the predominant means by which magnocellular neurons regulate vasopressin synthesis.

Animals↗
PubMed1992

Comparison of haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell transplants, autologous bone marrow transplants and allogeneic bone marrow transplants.

The haematological recovery time, infection rate and supportive care requirements of patients receiving recovery phase autologous peripheral blood stem cell transplants (APBSCT) (n = 38), autologous bone marrow transplants (autoBMT) (n = 13) and allogeneic bone marrow transplants (alloBMT) (n = 14) were compared with respect to the time post-transplant to reach 0.1, 0.5 and 2.0 x 10(9) neutrophils/l and 50 and 150 x 10(9) platelets/l, the length of hospitalization, fever and antibiotic use, the incidence of documented infection and the number of red cell and platelet transfusions. The APBSCT group had a significantly more rapid recovery of neutrophils and platelets and their supportive care requirements were significantly less than the autoBMT and the alloBMT groups. There was no difference between the latter two groups. The most significant variables contributing to the differences in haematological recovery times were the granulocyte-macrophage progenitor (CFU-GM) dose infused and, to a lesser extent, patient age. The APBSCT group received a higher CFU-GM dose of 87 +/- 12 x 10(4)/kg BW compared with 12 +/- 5 and 17 +/- 3 x 10(4)/kg BW in the autoBMT and the alloBMT groups, respectively (p = 0.0001). Patient age showed a negative correlation with the rate of recovery because the APBSCT group, which recovered faster was also older (48 +/- 2 years, compared with 33 +/- 3 and 31 +/- 2, respectively, p = 0.0001). On multivariate analysis, CFU-GM dose was the only variable to show a significant correlation with all the haematological recovery endpoints studied in these 65 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Youth attending Cape Peninsula day hospitals. Sexual behaviour and missed opportunities for contraception counselling.

Questionnaires were completed by a sample of youth (aged 15-24 years) attending day hospitals in the Cape Peninsula. Of the total sample of 225, 73.3% indicated that they had experienced sexual intercourse; of these, 27.3% had had 2 or more partners in the previous year, and on their last coital episode 91.0% had known their partner for more than 7 days and 52.8% had used some form of contraception. The criteria of a strict definition of missed opportunity for contraception intervention were fulfilled by 7.6% of the total sample, while 43.6% of those who had experienced sexual intercourse and 43.9% of those who had not did not receive contraception intervention but would have liked to have done so. Those who had had more than one partner in the previous year were more likely to have satisfied the strict definition of missed opportunity, while of those who had not had sexual intercourse, younger respondents and students were more likely not to have received contraception intervention despite wanting such intervention. It is concluded that all youth attending day hospitals should routinely be offered contraception counselling and that the issue of sexually transmitted diseases should be addressed simultaneously.

Adolescent↗
PubMed1991

Developments in the management of superficial fungal infections.

In the common superficial mycoses, caused by the dermatophytes and by Candida spp., the established agents, amphotericin B and griseofulvin (themselves important advances over the previously available simple topical preparations) have been limited in effectiveness in some situations. The introduction of the azole group of drugs, with a broad spectrum of activity and availability in varied preparations, has diversified the treatment possibilities in dermatophytoses and candidosis, and also in pityriasis versicolor and related conditions. Two other introductions appear promising: terbinafine has been very effective in early trials in dermatophytoses, and amorolfine may have a particular role in isolated nail infection, whether caused by dermatophytes or by less common fungi.

Animals↗
PubMed1991

In situ processing of a retroviral nucleocapsid protein by the viral proteinase.

The proteolytic processing pathway of the nucleocapsid protein (NC) by the viral proteinase within intact capsids of equine infectious anemia virus (EIAV) is presented. The cleavage sites are located at the carboxyl side of the first cysteine residue within the zinc-finger domains. EIAV is used as a model to predict similar NC cleavages in other retroviruses, including human immunodeficiency virus (HIV). The observed cleavages suggest a previously unrecognized function of the retroviral proteinase that may be crucial for replication during the early stages of the virus life-cycle (i.e. reverse transcription/integration).

Amino Acid Sequence↗
PubMed1991

Vasopressin transport regulation is coupled to the synthesis rate.

Vasopressin is synthesized in the perikarya of magnocellular neurons and is transported down long axons to the storage terminals of the posterior pituitary. To maintain stable pituitary stores following vasopressin secretion, the hypothalamus must synthesize and transport an amount of new vasopressin, equivalent to the amount released. Vasopressin release and synthesis rate can be chronically upregulated or suppressed relative to basal levels, depending on the demand for vasopressin. We studied whether vasopressin transport was similarly regulated during situations of varying demand. During chronic hyponatremia, when synthesis of vasopressin was reduced to undetectable levels, transport of vasopressin was also markedly decreased, as evidenced by continued presence of vasopressin in the transport system. Upregulation of transport was demonstrated by measuring pituitary accumulation of vasopressin in rats whose pituitary stores were initially depleted by hypernatremia and in whom subsequent release was suppressed by hyponatremia. In hypernatremic rats, transport of vasopressin was increased fivefold over baseline as determined by pituitary accumulation, and this elevated rate persisted for 7 days in the absence of release. This study demonstrates that axonal transport of vasopressin is a regulated process and is linked to synthesis rate rather than release.

Animals↗
PubMed1990

Substitution of proline with pipecolic acid at the scissile bond converts a peptide substrate of HIV proteinase into a selective inhibitor.

The nonapeptide H-Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-NH2 containing the retroviral Tyr-Pro cleavage site is a good substrate for the proteinase of human immunodeficiency viruses but it is not readily hydrolyzed by other nonviral proteinases including the structurally related pepsin-like aspartic proteinases. Replacing the Pro by L-pipecolic acid (2-piperidinecarboxylic acid) converted the substrate into an effective inhibitor of HIV-1 and HIV-2 proteinases with IC50 of approximately 1 microM. This compound showed a high degree of selectivity in that it did not inhibit cathepsin D and renin.

Amino Acid Sequence↗
PubMed1990

Edinburgh trial of screening for breast cancer: mortality at seven years.

Between 1979 and 1981, 45,130 women in Edinburgh aged 45-64 were entered into a randomised trial of breast cancer screening by mammography and clinical examination. The initial attendance rate was 61% but this varied according to age and socioeconomic status and decreased over succeeding years. The cancer detection rate was 6.2 per 1000 women attending at the first visit; the rate fell to around 3 per 1000 in the years when mammography was routinely repeated and to around 1 per 1000 at the intervening visits with clinical examination alone as the screening method. After 7 years of follow-up the mortality reduction achieved was 17% (relative risk = 0.83, 95% CI 0.58-1.18), which was not statistically significant, even when corrected for socioeconomic status. In women aged 50 years and over a mortality reduction of 20% was achieved.

Age Factors↗
PubMed1990

Mobile breast screening: factors affecting uptake, efforts to increase response and acceptability.

In 1986, a breast screening project was set up to assess the feasibility of mobile breast screening in rural areas near Edinburgh. Secondary objectives included a study of factors affecting uptake, ways in which uptake might be encouraged and a study of the acceptability of this form of screening. This paper deals with the results of studies dealing with secondary objectives. We found that response rates to opportunistic screening was poor, 5,631 attenders out of 23,229 eligible women (24.2%). This was especially so in older women. Distance proved to be the single most significant factor affecting uptake, but car and house ownership were also highly significantly correlated with response. Leaflet drops had no demonstrable effect on response, but personal invitation by general practitioners produced a 75% response rate in women 50-64 who had failed to attend on the van's previous visit. Attenders found this form of screening both convenient and acceptable.

Adult↗