PubMed HealthSearch

Biomedical subjects

P J Brooks

Publications and source records attributed to P J Brooks.

At least 19 recordsLinked to original sources

Local morphine withdrawal increases c-fos gene, Fos protein, and oxytocin gene expression in hypothalamic magnocellular neurosecretory cells.

We measured stimulation of c-fos and oxytocin gene expression during excitation of oxytocin cells induced by systemic or local morphine withdrawal. Female rats were made morphine-dependent by intracerebroventricular morphine infusion over 5 d. Morphine withdrawal, induced by systemic injection of the opioid antagonist naloxone (5 mg/kg) in conscious or anesthetized rats, increased the density of c-fos messenger RNA and of oxytocin heterogeneous nuclear RNA in supraoptic nucleus cells compared with those of nonwithdrawn rats; c-fos messenger RNA was also increased in the magnocellular and parvocellular paraventricular nuclei of withdrawn rats. Morphine withdrawal increased the number of Fos-immunoreactive cells in the supraoptic and magnocellular paraventricular nuclei of conscious or pentobarbitone-anesthetized rats. Morphine withdrawal also increased Fos-immunoreactive cell numbers in the parvocellular paraventricular nucleus of conscious but not anesthetized rats. Central administration of the alpha(1)-adrenoreceptor antagonist benoxathian (5 microg/min) did not prevent morphine withdrawal-induced increases in the numbers of Fos-immunoreactive neurons in the supraoptic or magnocellular paraventricular nucleus. Unilateral microdialysis administration of naloxone (10(-5) M) into the supraoptic nucleus of anesthetized morphine-dependent rats increased Fos-immunoreactive cell numbers compared with the contralateral nucleus. Finally, we investigated whether dependence could be induced by chronic unilateral infusion of morphine into a supraoptic nucleus; systemic naloxone (5 mg/kg) increased Fos-immunoreactive cell numbers in the morphine-infused nucleus compared with the contralateral nucleus. Thus, morphine withdrawal excitation increases c-fos and oxytocin gene expression in supraoptic nucleus neurons. This occurs independently from excitation of their ascending noradrenergic inputs, and both dependence and withdrawal can be induced within the supraoptic nucleus.

Adrenergic alpha-Antagonists

Paediatric nosocomial urinary tract infection at a regional hospital.

From a total of 26,603 admissions to the paediatric wards, 1360 paediatric nosocomial urinary tract infections (PNUTI) were identified during a 5-year retrospective chart review at the SFGH. The ages ranged from 3 days to 13 years, with 46% boys and 54% girls. The highest rates of PNUTI per service per 100 admissions were seen in the nursery (11.28) followed by paediatric surgery (2.89) and paediatric medicine (2.86). Although the greatest number of PNUTI occurred in the nursery, comparison between the years was not statistically significant. About 90% (1218 of 1360) of PNUTI occurred in catheterized patients. No documentation was found specifying the type of catheterization (intermittent or continuous). About 90% (1210 of 1360) of isolates were single organisms with Escherichia coli, Proteus mirabilis, Klebsiella spp. and Group B streptococci accounting for a total of approximately 70% of all pathogens. However, the composition of the most common isolate in each service differed. The most common isolate in the nursery was E. coli, in the paediatric medical and surgical services the most common isolates were Klebsiella spp. and Proteus mirabilis, respectively. Proteus mirabilis was isolated predominantly from boys with structural abnormality of the urethral tract. No PNUTIs were complicated by bacteraemia. The antibiotics with least effectiveness (in increasing order) for UTIs were cephalexin, ampicillin, trimethoprim, co-trimoxazole and tetracycline. The most effective antibiotics were nalidixic acid, gentamicin and amoxicillin-clavulanic acid.

Adolescent

Young children learn to produce passives with nonce verbs.

Younger and older children (mean ages = 2 years 11 months and 3 years 5 months) learned 2 nonce verbs in a full passive or active transitive construction. When asked patient-focused questions encouraging passive-voice replies (e.g., "What happened to the ball?") or agent-focused questions encouraging active-voice replies (e.g., "What did Elmo do?"), children used a variety of strategies to meet the demands of the questions, usually without changing the construction in which the verb occurred. In Study 2 in which passive and active constructions were primed, 40% of the almost 3-year-old children used an active-introduced verb in a passive construction and 35% used a passive-introduced verb in an active transitive construction when discourse demands encouraged them to do so. Thus, before their 3rd birthdays, some children have an understanding of the passive and active transitive constructions general enough to support productive usages with newly learned verbs.

Age Factors

Stimulation of expression of the oxytocin gene in rat supraoptic neurons at parturition.

We measured expression of the oxytocin gene in the supraoptic nucleus (SON) during pregnancy, parturition and lactation to examine its relationship to states of accumulation or depletion of oxytocin stores and to conditions of strong excitation of oxytocin neurons. The primary transcript (heterogeneous nuclear RNA, hnRNA) of the oxytocin gene was measured using a 3H-cDNA probe against intron 1 for in situ hybridisation. Autoradiographs of the SON showed the hnRNA as discrete clumps of silver grains within the nucleus of each neuron. The number of cells expressing oxytocin hnRNA did not change during pregnancy but increased during parturition; 10-day lactating animals showed similar increases. Oxytocin mRNA was also measured by in situ hybridisation using a 3H- or 35S-labelled oligonucleotide probe against exon C: hybridisation was seen over the cytoplasm of supraoptic neurons, but no differences were measured between virgin, mid-pregnant, preparturient, parturient or 2-day lactating rats. The data suggest that enhanced oxytocin gene transcription is not necessary to increase oxytocin stores in pregnancy. However, acute stimulation of magnocellular oxytocin neurons at parturition, which strongly increases neuron activity and secretion, results in a rapid increase in the number of cells expressing oxytocin hnRNA, and increased expression is sustained in lactation.

Animals

Expression of long-patch and short-patch DNA mismatch repair proteins in the embryonic and adult mammalian brain.

Expression of the DNA mismatch repair (MMR) pathway was examined in the adult and developing rat brain. Rat homologues of human GTBP and MSH2, which are essential components of the post-replicative DNA MMR system, were identified in nuclear extracts from the adult and developing rat brain. Developmental studies showed that both GTBP and MSH2 levels were higher in nuclei isolated from the embryonic brain (day 16) than adult brain. However, this difference was not as dramatic as the difference in the number of proliferating cells. Levels of thymine DNA glycosylase (TDG), the enzyme which catalyzes the first step in short patch G:T mismatch repair, were also decreased in adult compared to embryonic brain. In the adult brain, MMR proteins were elevated in nuclear extracts enriched for neuronal nuclei. These results suggest that adult brain cells have the capacity to carry out DNA mismatch repair, in spite of a lack of ongoing DNA replication.

Animals

Detection of excision nuclease in cell-free extracts from the adult mammalian brain.

The autosomal recessive disorder xeroderma pigmentosum (XP) results from defects in the nucleotide excision repair (NER) pathway for DNA repair. NER normally repairs bulky DNA lesions, such as pyrimidine dimers resulting from UV radiation. XP patients have high rates of skin cancer, and some also develop progressive neurological degeneration. To better understand the mechanism of this neurodegeneration, I used a specific assay for the multicomponent excision nuclease of the NER pathway in cell-free extracts from the adult rat brain. Excision nuclease activity was detectable in whole-cell extracts prepared from the cerebellum, whereas extracts prepared from the forebrain, which has a lower density of cell nuclei, had much less activity. Nuclear extracts from both areas were equally capable of restoring activity to extracts from two different NER-deficient cell lines, despite large differences in the ratio of neurons to nonneuronal cells in the cerebellum and forebrain. These results indicate that the NER pathway is functional in neuronal cells in the adult brain. The implications of this finding for XP and other neurodegenerative diseases is discussed.

Animals

Nosocomial infections in a rural regional hospital in a developing country: infection rates by site, service, cost, and infection control practices.

OBJECTIVE: To assess the prevalence of nosocomial infections at a rural government hospital from 1992 to 1995. DESIGN: Retrospective review of data from 1992 to 1995 regarding rates of nosocomial infections, cost to government, and infection control practices. SETTING: 653-bed rural hospital providing primary and tertiary care. PATIENTS: Patients admitted to the hospital between 1992 and 1995 who were found with hospital-acquired infections during their stay. INTERVENTIONS: None. RESULTS: Over the 4-year period, 7,158 nosocomial infections were identified from 72,532 patients (10.0/100 admissions). High nosocomial infection rates were found on the intensive-care unit (67/100 admissions), urology (30/100 admissions), neurosurgery (29.5/100 admissions), and newborn nursery (28.4/100 admissions). Urinary tract infections (4.1/100 admissions) accounted for most nosocomial infections (42%), followed by postoperative wound infections (26.8%) with a rate of 2.6/100 admissions. Nosocomial pneumonias and bloodstream infections also were common with 13.2% and 8.0%, respectively. The highest rates occurred on the intensive-care unit for both pneumonia (26.4/100 admissions) and bloodstream infection (7.0/100 admissions). The cost to the government for nosocomial infections was estimated at US $697,000 annually (US $1=$6 Trinidad and Tobago). Poor infection control practices, inadequate handwashing facilities, lack of supplies, and nonexistent garbage cans on most wards were quite evident. CONCLUSIONS: Strict adherence to proper infection control practices, such as handwashing techniques, and improvement of facilities are crucial steps in preventing cross-infections in the hospital environment. Implementing these measures may substantially reduce the massive drain on the hospital budget in treating nosocomial infections. The saved revenue could go toward improvement of ward facilities and reduction of overcrowding, thus further reducing cross-infection.

Cross Infection

Widespread expression and estrogen regulation of PPEIA-3' nuclear RNA in the rat brain.

We previously identified a novel nuclear RNA species derived from the preproenkephalin (PPE) gene. This transcript, which we have named PPEIA-3' RNA, hybridizes with probes directed at a region of PPE intron A downstream of an alternative germ-cell transcription start site, but does not contain PPE protein coding sequences. We now report that estrogen treatment of ovariectomized rats increases the expression of conventional PPE heteronuclear RNA, and also induces the expression of PPEIA-3' RNA, apparently in separate cell populations within the ventromedial nucleus of the hypothalamus. Further, we show that cells expressing PPEIA-3' are found in several neuronal groups in the rat forebrain and brainstem, with a distinct topographical distribution. High densities of PPEIA-3' containing cells are found in the reticular thalamic nucleus, the basal forebrain, the vestibular complex, the deep cerebellar nuclei, and the trapezoid body, a pattern that parallels the distribution of atypical nuclear RNAs described by other groups. These results suggest that this diverse neuronal population shares a common set of nuclear factors responsible for the expression and retention of this atypical RNA transcript. The implication of these results for cell-specific gene transcription and regulation in the brain and the possible relationship of PPEIA-3' RNA and other atypical nuclear RNAs is discussed.

Animals

Preproenkephalin mRNA is regulated by an interaction between steroid hormones and nociceptive stimulation.

The expression of preproenkephalin (PPE) mRNA has previously been shown to be regulated by steroid hormones in the ventromedial nucleus of the hypothalamus (VMH) and to be regulated by noxious stimuli in the dorsal horn of the spinal cord (DH). The present in situ hybridization study in ovariectomized rats showed that PPE mRNA expression in both the VMH and the lumbar DH, responds to the interaction between a noxious peripheral stimulus and ovarian steroid hormones. In the VMH, either estradiol or estradiol + progesterone increased the mean PPE mRNA content per cell by 100% compared with vehicle-treated rats. Unilateral hindpaw injection of 5% formalin, as compared to saline, significantly increased mean PPE mRNA content per VMH cell in rats treated with vehicle or estradiol but not those treated with estradiol + progesterone. Regression analysis for mean PPE mRNA content per VMH cell as a function of intensity of hindpaw inflammation showed a significant positive correlation coefficient after vehicle and estradiol treatment (P < 0.02) but a strong trend towards a negative correlation coefficient after estradiol + progesterone treatment (P < 0.06). ANOVA for homogeneity of regression coefficients showed a significant difference across hormone groups (P < 0.01). In the lumbar DH, mean PPE mRNA content per cell was greater in rats injected with formalin than with saline and was greatest in rats given steroids + formalin. Mean PPE mRNA content per DH cell was greater ipsilateral than contralateral to the formalin injection in estradiol-treated rats, but no laterality difference was seen in the other hormone groups. No significant differences in mean PPE mRNA levels per DH cell were found among the rats treated with saline + hormone, saline + vehicle, formalin + vehicle, or uninjected rats. For all hormone groups combined, mean PPE mRNA per DH cell showed a significant positive regression on intensity of hindpaw inflammation (P < 0.05). Taken together these data are consistent with reports of increased pain threshold during pregnancy, descending control of antinociception from the basomedial hypothalamus and positive correlations between VMH levels of PPE mRNA and lordosis, a behavior evoked by somatosensory stimulation below nociceptive threshold.

Animals

Human articular cartilage storage in cell culture medium: guidelines for storage of fresh osteochondral allografts.

The viability of transplanted articular cartilage is one of the determinants of outcome following the transplantation of osteochondral allografts. Disappointing results from cryopreservation have led to the practice of fresh transplantation of articular segments, especially for posttraumatic defects. To date, no studies have demonstrated in vitro viability rates for refrigerated human cartilage awaiting transplantation. This study evaluates the effects of storage on the viability of human chondrocytes using cell culture medium. Human articular cartilage obtained from notchplasties was stored for up to 48 hours in cell culture medium. Radioactive 35S-sulfate uptake was determined at 0, 24, and 48 hours, as a measure of protein, synthesis, and chondrocyte viability. Specimens were stored at 4 degrees C in culture medium. Results showed an average decrease in 35S-sulfate uptake of 0.8% at 24 hours and 6.4% at 48 hours, indicating a high level of chondrocyte viability after refrigeration. Because transplantation typically is performed within 24 hours of tissue harvest, it appears that nearly 100% of chondrocytes should survive fresh transplantation.

Cartilage, Articular

DNA damage, DNA repair, and alcohol toxicity--a review.

Alcohol (ethanol) is clearly a toxic substance when consumed in excess. Chronic alcohol abuse results in a variety of pathological effects, including damage to the liver and brain, as well as other organs, and is associated with an increased risk of certain types of cancers. Alcohol consumption by pregnant women can result in fetal alcohol effects and fetal alcohol syndrome. All of these toxic effects are well documented. What is needed at present is a complete understanding of the molecular mechanisms by which alcohol causes these toxic effects. Such an understanding may lead to better treatments of some of these toxic effects. This review, focuses on the possibility that toxic effects of ethanol are mediated, at least in part, by damage to DNA. In particular, I emphasize data on the production of endogenous DNA-damaging molecules as a result of alcohol consumption and metabolism. Specific examples of DNA-damaging molecules to be considered are reactive oxygen species, including oxygen radicals, lipid peroxidation products, and acetaldehyde. The relevant DNA repair pathways that protect cells against DNA damage produced by these molecules will also be reviewed. The goal of this review is to integrate recent results from the fields of mutagenesis and DNA repair with the alcohol toxicity literature, with the aim of stimulating research into the role of DNA damage in different types of alcohol toxicity and the role of DNA repair in protecting cells from alcohol-related damage.

Animals

DNA mismatch repair and DNA methylation in adult brain neurons.

DNA repair is essential for maintaining the integrity of the nucleotide sequence of cellular DNA over time. Although much information has accumulated recently on the mechanisms of DNA repair in cultured cells, little is known about the DNA repair capabilities of cells in the adult brain. In the present study, we have investigated the capacity of nuclear extracts from adult rodent brain neurons to carry out DNA mismatch repair. We focused on the repair of G.T and G.U mismatches, which are caused by deamination of 5-methyl cytosine to thymine, or cytosine to uracil, respectively, because these are the only types of mismatches that can arise in nondividing cells. We found that nuclear extracts from adult brain neurons can correct G.T and G.U mismatches, restoring them to G:C base pairs. Several other types of DNA mismatches could not be processed. These data provide the first direct demonstration that neurons in the adult mammalian brain have the capability to carry out DNA mismatch repair. We also we report that adult brain contains high levels of DNA methyltransferase (MTase) activity. We propose that one function of DNA MTase in the adult brain is to remethylate newly incorporated cytosine residues from G.T mismatch repair after deamination of 5-methyl cytosine, thereby maintaining the original pattern of DNA methylation. The high levels of brain DNA MTase suggest further that this enzyme has additional functions in the brain.

5-Methylcytosine

What do children know about the universal quantifiers all and each?

Children's comprehension of the universal quantifiers all and each was explored in a series of experiments using a picture selection task. The first experiment examined children's ability to restrict a quantifier to the noun phrase it modifies. The second and third experiments examined children's ability to associate collective, distributive, and exhaustive representations with sentences containing universal quantifiers. The collective representation corresponds to the "group" meaning (for All the flowers are in a vase all of the flowers are in the same vase). The distributive representation implies a pairing (e.g., each flower paired with a vase for Each flower is in a vase). The exhaustive representation exhausts both sets (e.g., for The flowers are in the vases all the flowers are in vases and all the vases have flowers in them). Four- to 10-year-olds children had little difficulty restricting the quantifier all to the noun it modified in a task which required them to attend to the group feature of all. In contrast, only 9- and 10-year-olds were able to solve the task when the quantifier was each and the pictures showed entities in partial one-to-one correspondence. Children showed a preference for associating collective pictures with sentences containing all and distributive pictures with sentences containing each. The results suggest that between the ages of 5 and 10 years, children's semantic representations undergo less radical changes than others have proposed. Instead, developmental change may occur gradually as children acquire linguistic cues which map onto existing semantic representations.

Analysis of Variance

An anxiolytic action of oxytocin is enhanced by estrogen in the mouse.

The established role of oxytocin (OT) in facilitation of steroid-modulated reproductive and affiliative behaviors led to the speculation that it may have anxiolytic actions under certain hormonal conditions. NIH-Swiss mice were tested for responsiveness to OT in two behavioral tests of anxiety, the holeboard apparatus and elevated plus-maze. Dose-response assessment indicated that 3 mg/kg was the optimal dose for peripherally administered (IP) OT on the elevated plus-maze. There were no consistent effects at any dose on the holeboard apparatus. In ovariectomized mice pretreated with estradiol (E2), peripherally administered OT increased the number of entrances onto the open arms, as well as the amount of time on the open arms compared to other groups (ANOVA; p < 0.05). There was little to no effect of OT in ovariectomized animals not pretreated with E2. When OT was administered intracerebroventricularly (ICV), there was an increase in entrances and time on the open arms compared to that of females infused with arginine vasopressin (AVP). This increase was apparent in ovariectomized females, but was further enhanced in those pretreated with E2 (ANOVA; p < 0.05). In contrast, the combination of E2 pretreatment and ICV AVP decreased the number of entrances and time spent on the open arms of the elevated plus-maze compared to those receiving OT, suggesting an estrogen-modulated anxiogenic action of AVP. Analyses of [125]I-OVTA binding density indicated a significant increase in binding density in the lateral septum of E2-treated females compared to OIL-treated controls (ANOVA; p < 0.05). There was no effect of E2 treatment on [125]I-OVTA binding density in the amygdala or ventromedial nucleus of the hypothalamus. Taken together, these data indicate that OT exerts an anxiolytic action that is enhanced in the presence of circulating estrogen. This behavioral effect may be mediated by estrogen-induced increases in OT binding density in the lateral septum and may be important to the facilitation of social interactions.

Animals

Factors motivating pharmacy students to pursue residency and fellowship training.

Factors that influence pharmacy students to pursue residency and fellowship training were studied. Directors of 514 residency or fellowship programs were asked to distribute to their residents or fellows a survey concerning factors that influenced their decision to enter a residency or fellowship. Deans of the 75 U.S. pharmacy schools were sent a related survey and asked to forward it to the faculty or staff member who was most involved in promoting residencies and fellowships to students. This survey asked about methods for promoting the programs and the faculty member's opinion on why students chose to become residents and fellows. Residents and fellows cited "to gain knowledge and experience," "recognition of new and challenging roles," and "desire for specialized training" as their leading reasons for entering their programs. The pharmacy school representatives also cited "to gain knowledge and experience" and "desire for specialized training" as leading reasons. The residents and fellows thought instruction on residencies and fellowships should occur earlier in the pharmacy degree programs than it was being provided. The pharmacy school respondents considered the largest barriers to entering such programs "financial" and "a job was available upon graduation from pharmacy school." The pharmacy school survey results were broken into two groups: the 9 schools that produced the most students who went on to residencies and fellowships, and the rest of the schools. The former group was more likely to offer the Pharm.D. degree and to involve preceptors, residents, and fellows in didactic and clerkship teaching. Two factors--"to gain knowledge and experience" and "desire for specialized training"--were cited most frequently by survey respondents as important factors in students' decisions to pursue residencies and fellowships, and schools that produce more residents and fellows tended to involve preceptors, residents, and fellows in didactic and clerkship training.

Adult

Estrogen modulation of mRNA levels for the two forms of glutamic acid decarboxylase (GAD) in female rat brain.

Two separate forms of glutamic acid decarboxylase, now termed GAD65 and GAD67, are the rate limiting enzymes for synthesis of gamma-aminobutyric acid (GABA). Because of the significance of GABA to neuroendocrine processes, numerous attempts have been made to determine the impact of gonadal steroids on enzyme functioning with inconclusive results. Therefore, we attempted to determine the impact of estradiol on mRNA levels for each form of GAD by quantitative in situ hybridization histochemistry in various brain regions. Ovariectomized rats were treated with estradiol benzoate or oil vehicle on 2 consecutive days and the brains collected on the third day. DNA probes specific for GAD65 and GAD67 were radiolabeled with CTP32 using asymmetric polymerase chain reaction. Results of in situ hybridizations for each probe on alternate sections from the same animals were analyzed for magnocellular preoptic area (McPOA), dorsal medial nucleus of the hypothalamus (DMN), zona incerta (ZI), and midbrain central gray (MCG). In the McPOA, estradiol exerted opposite effects on the frequency distribution of pixels per cell for two GAD mRNA probes, significantly increasing GAD65 (P < .05) and decreasing GAD67 (P < .01; Kolmogorov-Smirnov). In the DMN, estradiol treatment significantly increased GAD67 by 60% (P < .05; two-way ANOVA) but decreased GAD65 mRNA by 73% (P < .01). Note the direction of effects are opposite between McPOA and DMN. In MCG, analysis showed no estradiol effect on GAD mRNA levels/cells, but the proportion of cells expressing detectable levels of GAD65 or GAD67 increased by 33-40% in estradiol-treated rats (chi 2, P < .001).

Animals

Changes in preproenkephalin messenger RNA level in the rat ventromedial hypothalamus during the estrous cycle.

To gain a better understanding of the relationship between the female rat reproductive system and preproenkephalin (PPE) expressing neurons under physiological conditions, we examined changes in PPE mRNA levels in the mediobasal hypothalamus during the rat estrous cycle by means of northern blotting and in situ hybridization histochemistry (ISHH). In the Northern blot studies, we found that PPE mRNA levels in the mediobasal hypothalamus were significantly increased by noon of proestrus compared to those in the morning and stayed high until diestrus day 1, and returned toward low levels on diestrous day 2. In contrast, measured as controls, glyceraldehyde-3-phosphate-dehydrogenase mRNA levels were significantly higher on proestrus regardless of time of day compared to diestrus day 2, and levels of calcineurin mRNA on proestrous and estrous were significantly lower than diestrous day 1 and day 2. ISHH studies revealed that these changes in PPE mRNA levels were specific in the ventromedial hypothalamic nucleus pars ventrolateralis (VMHVL), since we could not see any significant changes in signal in other parts including ventromedial hypothalamic nucleus pars dorsomedialis and arcuate hypothalamic nucleus. In the VMHVL, PPE mRNA levels in the afternoon of proestrous were significantly higher than those in the afternoon of diestrous day 2 whereas no significant change in PPE mRNA was observed in the caudate-putamen. The present study provides additional information relevant to possible implications of PPE gene expression in female reproductive systems, since changes in PPE mRNA levels may be associated with estrogen as well as progesterone or other hormonal concentrations during the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The evolution of pharmacy residency training programs and corresponding standards of accreditation.

Practice-based pharmacy training has a long history, particularly in institutional pharmacy practice. Formal pharmacy residency training programs and accreditation standards were first developed in the early 1960s. Practitioners now practice in a much different environment. Residency programs and accreditation standards have changed dramatically to meet the needs of practitioners, patients, and employers. The authors trace the evolution of programs from general internships through clinical practice and specialty residencies and fellowships and the development of standards and competency-based training.

Accreditation