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Biomedical subjects

J Brooks

Publications and source records attributed to J Brooks.

At least 55 records · Page 3Linked to original sources

Detection of prolactin receptor gene expression in the sheep pituitary gland and visualization of the specific translation of the signal in gonadotrophs.

In sheep, as in other mammalian species, the pronounced reduction in GnRH and gonadotropin secretion that characterizes stages of infertility is normally associated with a conspicuous increase in the secretion of PRL. A possible role of PRL in modulating gonadotropin release implies the presence and activation of specific receptors in target tissues (i.e. pituitary, hypothalamus). In this study, we investigated the expression of PRL receptor (PRL-R) messenger RNA (mRNA) in the sheep pituitary and the distribution of the translated product in specific pituitary cell types. Using primers designed to flank different regions of the extracellular and cytoplasmic domains of the PRL-R, two complementary DNA (cDNA) fragments, one of which was specific for the long-form PRL-R, were amplified by reverse transcriptase-PCR. Sequencing revealed more than 95% identity with nucleotides 267-1272 of the bovine PRL-R cDNA. When these cDNA fragments were used as probes for the detection of PRL-R mRNA expression by Northern analysis, three major transcripts of approximately 13, 10, and 3.5 kb were identified in the pituitary. Both probes detected identical transcripts, suggesting that primarily the long form of PRL-R is expressed in the sheep pituitary gland. No difference in the abundance of pituitary PRL-R mRNA transcripts was observed between anestrous and breeding season ewes (P > 0.05). Additional RT-PCR studies revealed the existence of a cDNA variant bearing a 39-bp insert with a premature stop codon. Translation of the PRL-R mRNA was confirmed by Western blot analysis. The identification of PRL-R in specific pituitary cell types was carried out by immunocytochemistry. Double immunofluorescent staining, using antibodies to the rat liver PRL-R and specific monoclonal antibodies to the LHbeta-subunit, FSHbeta-subunit, free alpha-subunit, PRL, or GH, revealed that in both the pars distalis and pars tuberalis, all pituitary cells expressing PRL-R immunoreactivity were positive for LHbeta, although only 53% of LHbeta-positive cells expressed PRL-R. A small proportion (2%) of gonadotrophs expressing PRL-R immunoreactivity were negative for FSHbeta, indicating the specific localization of PRL-R in LH (or LH/FSH) secreting cells. Further, a selective cytological association was detected in the pars distalis where LH gonadotrophs appeared surrounded by lactotrophs. In contrast to these observations, PRL-R immunoreactivity was completely absent in lactotrophs and in the vast majority (>98%) of somatotrophs. In conclusion, here we show the expression of PRL-R mRNA in the sheep pituitary and the specific translation of the signal in LH (or LH/FSH) gonadotrophs. These results support the hypothesis that PRL may be involved in the regulation of gonadotropin secretion through a paracrine mechanism within the pituitary gland and that this action does not seem to be mediated by changes in PRL-R mRNA expression.

Animals↗

Localization and temporal expression of prolactin receptor in human endometrium.

Extrapituitary PRL is synthesized by the decidualized endometrial stromal cells from the mid to late secretory phase in the nonpregnant cycle and throughout pregnancy. The function of PRL in the uterus is unknown, but the temporal expression indicates a role in implantation and placentation. PRL is a powerful immunoregulatory agent, and thus, a role in modulating endometrial leukocytes may be envisaged. To investigate the site of action of PRL, immunohistochemistry was conducted to localize the PRL receptor (PRL-R). In addition, ribonucleic acid was extracted and reverse transcriptase-PCR for PRL-R was conducted. PRL-R protein was immunolocalized to the glandular epithelium and a subset of stromal cells from the mid to late secretory phase of the menstrual cycle and in early decidua. PRL-R transcripts were also detected from the late secretory phase and first trimester decidua. These findings indicate that the receptor is expressed in a temporal pattern similar to that of PRL. PRL-R expression in the glandular epithelium is consistent with a role in regulating glandular activity. Furthermore, immunoreactivity for PRL-R in a subset of stromal cells may be evidence for paracrine interactions between decidualized cells or an immunoregulatory role for PRL.

Decidua↗

Factorial structure of the Wisconsin Card Sorting Test.

This study examined the factorial structure of the Wisconsin Card Sorting Test (WCST) in normal university students (N = 135) and a mixed clinical sample (N = 139). Two highly stable orthogonal factors were observed accounting for 70 and 21 per cent of the variance, respectively. Factor I was interpreted as reflecting undifferentiated executive function while Factor II may measure cognitive abilities associated with attentional function. This work can serve as the basis for further examination of the construct validity of the WCST and has implications for its use.

Adult↗

Red Cross only positive result of horrifying 1859 bloodbath.

Haunted by the suffering and human devastation he witnessed after the 1859 Battle of Solferino in Italy, Swiss banker Henry Dunant wrote a book that galvanized European governments and resulted in the first international agreement that established rules for the conduct of war. The Geneva Convention also resulted in the formation of the Red Cross.

Europe↗

The sad and tragic life of Typhoid Mary.

As society grapples with contemporary moral questions raised by the barring of HIV-infected people from jobs and even crossing some national borders, it is probably useful to re-examine the case of Typhoid Mary. The case of Mary Mallon shows how an earlier age resolved the conflict that arises when society's right to protect itself from unnecessary exposure to disease impinges on the liberty of individual citizens.

Carrier State↗

The California Card Sorting Test may dissociate verbal and non-verbal concept formation abilities.

Most neuropsychological measures of executive function provide only global indices of performance and are relatively insensitive to lateralized dysfunction. The present paper presents a right temporal lobectomy patient whose performance indicates that the California Card Sorting Test, a new measure of executive function, may dissociate verbal and non-verbal concept formation abilities. This case highlights the potential research and clinical value of this test compared to that of existing tests of executive function.

Adult↗

Epidemiology and patterns of hospital use after parasuicide in the south west of England.

OBJECTIVE: To describe the epidemiology, management, and outcome of parasuicide in the south west of England. DESIGN: Descriptive analysis using routine information systems. SETTING: The former South Western Regional Health Authority, population aged 10 and over: 2.9 million. SUBJECTS: These comprised 5080 residents of the South Western Health Region, admitted on 5770 occasions for parasuicide between April 1992 and March 1993 to hospitals in the south west. MAIN OUTCOME MEASURES: Person based age and sex standardised admission ratios for parasuicide; readmission for parasuicide in the subsequent 12 months; admission to psychiatric hospital after parasuicide; in-hospital mortality for those admitted after attempted suicide. RESULTS: The overall rate of parasuicide admission was 174 per 100,000 per year. Rates were highest in males aged 20-24 (381 per 100,000) and in females aged 15-19 (625 per 100,000). Parasuicide is the third most frequent cause of acute medical admission in the south west. A total of 10.0% of admissions received psychiatric inpatient care as a direct result of their parasuicide admission and 10.1% were readmitted in the following 12 months with a repeat episode of parasuicide. Significant variations in standardised admission ratios for parasuicide were observed between the districts. Some of this variation is related to socioeconomic differences between districts, the rest is probably due to differences in practice between districts. There is no clear evidence that these variations result in differences in readmission rates. Districts where psychiatric inpatient facilities were located on the same site as the general hospital tended to admit a greater percentage of parasuicide patients for psychiatric inpatient care. A quarter of all suicide deaths from overdose occurred in hospital. It is estimated that there are 87,000 parasuicide admissions in England and Wales annually. CONCLUSIONS: Parasuicide is a common cause of acute hospital admission and there is evidence that hospital admission practices for parasuicide vary across the south west. Randomised controlled trials are needed to evaluate the most appropriate form of management for those patients who do not require admission on medical grounds.

Adolescent↗

Effects of H1- and H2-antihistamines on platelet-activating factor and bradykinin-induced inflammatory responses in human skin.

Previous studies show that oral antihistamines affect the weal and flare response to intradermal injections of the inflammatory mediators platelet-activating factor (PAF) and bradykinin (BK). The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on weal and flare responses to PAF and BK in healthy non-atopic human volunteers. The effects of doxepin on PAF responses were investigated, as there is evidence that doxepin may have direct anti-PAF effects in addition to its known antihistaminic actions. Terfenadine significantly reduced weal and flare responses to PAF (mean reduction 53 and 73%, respectively) and flare responses to BK (mean reduction 78%) but had no effect on weal responses to BK. Doxepin significantly reduced both weal and flare responses to PAF (mean reduction 43 and 68%, respectively, at higher doses of PAF). Cimetidine had no effect on weal or flare responses to PAF or BK. These findings suggest that the flare response to intradermal BK is mediated via histamine release while the weal response is not. The effects of the various antagonists of PAF-induced responses suggest that its effects too may be mediated via histamine, the similarity of the effects of terfenadine and doxepin on these responses indicating that the effects of doxepin may be due to its known antihistamine activity rather than to any specific PAF-antagonistic properties. Platelet-activating factor (PAF) is a phospholipid which is released from a wide range of cell types and also from vascular endothelium. PAF is formed by the conversion of ether-linked phospholipids initially to the biologically inactive lyso-PAF and then by acetylation to PAF. Intradermal injection of PAF in human skin causes vasodilatation and increased vascular permeability, producing a weal and flare response with accompanying pruritus. Bradykinin (BK) is a vasoactive polypeptide formed by the action of enzymes known as kallikreins on inactive precursors called kininogens. Its effects include an increase in blood flow and vascular permeability and stimulation of the release of prostaglandins and histamine. On intradermal injection in human skin it causes a weal and flare response with associated pain rather than pruritus. Previous studies have suggested that the weal and flare response to PAF may be mediated in part by histamine release. Given that BK is known to cause histamine release it appears possible that the responses to both compounds may be modified by conventional antihistamines. Experiments based on this premise have found that antihistamines have a pronounced effect on the flare response to PAF but a less marked effect on weal responses. The weal response to BK was unaffected by systemic antihistamines but studies have produced conflicting results with regard to effects on the flare response. The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on PAF- and BK-induced weal and flare responses in healthy, non-atopic human volunteers. Based on the treatment of cold urticaria it has been suggested that doxepin, which has known H1- and H2-antagonistic effects, may in addition show specific anti-PAF activity. We compared the effects of doxepin on PAF-induced intradermal responses with those of terfenadine and cimetidine in this study.

Administration, Oral↗

Relation between parasuicide, suicide, psychiatric admissions, and socioeconomic deprivation.

OBJECTIVE: To examine the relations between parasuicide, suicide, psychiatric inpatient admissions, and socioeconomic deprivation. DESIGN: Ecological analysis with data from routine information systems and the 1991 census. SETTING: 24 localities in the area covered by the Bristol and District Health Authority (population 817,000), consisting of aggregations of neighbouring wards, with an average population of 34,000. SUBJECTS: 6089 subjects aged over 10 years admitted to hospital after parasuicide between April 1990 and March 1994; 997 suicides occurring 1982-91; 4763 subjects aged 10-64 years admitted with acute psychiatric illness between April 1990 and March 1994. RESULTS: Localities varied significantly in standardised admission ratios for parasuicide and standardised mortality ratios for suicide (P < 0.001). Spearman's rank correlation coefficient between the standardised mortality ratio for suicide and standardised admission ratio for parasuicide was 0.73 (95% confidence interval 0.46 to 0.88). Correlation between parasuicide and Townsend score was 0.86 (0.70 to 0.94) and between suicide and Townsend score 0.73 (0.46 to 0.88). The partial correlation coefficient between suicide and parasuicide after the Townsend score was adjusted for was 0.29 (-0.13 to 0.62). The correlation between standardised admission ratio for parasuicide and standardised admission ratio for psychiatric illness was 0.76 (0.51 to 0.89) and between standardised mortality ratio for suicide and standardised admission ratio for psychiatric illness was 0.72 (0.45 to 0.87). CONCLUSION: A strong ecological association exists between suicide and parasuicide, with socioeconomic deprivation accounting for much of this relation. This strong association provides supporting evidence for the importance of social policy measures in attaining Health of the Nation targets on mental health.

Adolescent↗

The pleckstrin homology domain in insulin receptor substrate-1 sensitizes insulin signaling.

The NH2 terminus of insulin receptor substrate-1 (IRS-1) contains a pleckstrin homology (PH) domain. We deleted the PH domain in IRS-1 (IRS-1 delta PH) and expressed the mutant in Chinese hamster ovary and 32D cells. During insulin stimulation, IRS-1 delta PH is poorly tyrosine-phosphorylated in CHO cells, but undergoes serine/threonine phosphorylation. Similarly, IRS-1 delta PH fails to undergo insulin-stimulated tyrosine phosphorylation in 32D cells, which uncouples the activation of phosphatidylinositol 3'-kinase and p70s6k from the endogenous insulin receptors. Overexpression of the insulin receptor in 32DIR cells, however, restores tyrosine phosphorylation of IRS-1 delta PH and rescues insulin responses including mitogenesis. Thus, while the PH domain is not required for the engagement of downstream signals, it is one of the elements in the NH2 terminus of IRS-1 that is needed for a sensitive coupling to insulin receptors, especially at ordinary receptor levels found in most cells and tissues.

Animals↗

Australia hopes new strategy will improve health services for aboriginal population.

Australia has embarked on a National Aboriginal Health Strategy that aims to give aboriginals equal access to health services by 2001. Although the harmful effects of colonization are now recognized, it is not possible to eradicate overnight the health problems resulting from 200 years of mistreatment and neglect, officials say. In implementing the strategy, the Australian government is spending $1.3 billion over 5 years to improve the basic infrastructure of housing, water, waste disposal, roads and communications in aboriginal communities, enhance health services and encourage more aboriginals to seek careers in health care.

Australia↗

American cigarettes have become a status symbol in smoke-saturated China.

Antismoking advocates often complain about smoking levels in Canada but our problems pale beside those of China, where it is estimated that 300 million people already smoke and more are being encouraged to do so by Western advertising. To its credit, the Chinese government is taking steps to discourage smoking as it prepares to host the 10th World Conference on Tobacco and Health in 1997. By 2025, smoking-related disease is expected to kill 2 million Chinese a year.

Advertising↗

Australia's Flying Doctors re-evaluate medical services needed in the outback.

Australia's fabled Royal Flying Doctor Service recently undertook a soul-searching evaluation of its structure, operations and goals. Although there are no plans to stop providing emergency medical services to the residents of the outback, the service may refocus efforts on health promotion and prevention, since 75% of its work involves nonemergency care. Cost efficiency, the key phrase for health care around the globe, will be another goal.

Adult↗

Characterization of two Epstein-Barr virus epitopes restricted by HLA-B7.

We have identified two epitopes for Epstein-Barr virus specific cytotoxic T lymphocytes (CTL) restricted by the common allele HLA-B7. They are EBNA 3C 881-9 (QPRAPIRPI) and EBNA 3A 379-387 (RPPIFIRRL). The epitopes conform well to the recently described motif for HLA-B7-binding peptides (Huckzo et al., J. Immunol. 1993. 151:2572). Titration of the peptides in CTL assays and detergent lysate binding assays revealed that extending the peptides at either the N or C terminus did not reduce their affinity for HLA-B7. This behavior contrasted with HLA-B51, which binds peptides with a similar motif to B7, and has identical amino acid residues at sites expected to form the "F" pocket of the peptide-binding groove. HLA-B51 also bound the peptide EBNA 3C 881-9, but was unable to bind peptides extended at the C terminus.

Amino Acid Sequence↗