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Biomedical subjects

R Green

Publications and source records attributed to R Green.

At least 595 records · Page 33Linked to original sources

Sex-dimorphic behaviour development in the human: prenatal hormone administration and postnatal socialization.

An interdisciplinary integrative approach must be utilized in the study of psychosexual differentiation. The approach must capitalize on data derived from non-human models, from experiments of nature, and from experiments of nurture. Studies from non-human primates strongly suggest the influence of prenatal sex hormone levels on postnatal sexually dimorphic behaviours. Starting from this basis we have studied sixty young adult men whose mothers received, during pregnancy, diethylstilboestrol, diethylstilboestrol and natural progesterone, natural progesterone, or synthetic progesterone. They have been compared with matched controls not exposed in utero to exogenous hormones. Studies of socialization patterns must document the differential developmental experiences, if any, of children with atypical and typical sex-typed behaviours. To this end, we are studying 60 boys whose behaviour before puberty was decidedly feminine, and their parents, and contrasting them with masculine boys and their parents. We are also studying 50 girls whose behaviour before puberty was 'masculine', and contrasting them with 'feminine' girls. Additionally, we are studying the sexually dimorphic behaviour of children of sexually atypical parents. The parents have either undergone sex-change surgery (male-to-female or female-to-male) or are homosexual. Data from the three studies are presented. A call is made to researchers working with non-human primates to test and extend these findings.

Child↗

Criteria for progressive modification of neurobehavioral batteries.

Six specific issues affecting the progressive modification of neurobehavioral test batteries used in field studies of populations exposed to neurotoxicants are discussed and test review recommendations are provided addressing each issue. The issues include: (a) general test review standards, (b) comprehensive assessment, (c) tailored batteries, (d) incorporation of new tests and techniques, (e) personnel and mechanisms for review, and (f) development of a battery assessing peripheral nervous system function.

Behavior↗

Primary isolation of the bovine spongiform encephalopathy agent in mice: agent definition based on a review of 150 transmissions.

In the epizootic of bovine spongiform encephalopathy (BSE) in Great Britain, the cattle in which a positive diagnosis was made numbered almost 180 000, but strain characterization was performed on only a very small sample of these cases. This report describes the results of BSE transmission to Prnp(a) mice from 150 transmission experiments at the Veterinary Laboratories Agency (VLA) over the last decade. These data, derived from a large sample of BSE-affected cattle, confirmed previous reports that show no evidence for diversity in BSE isolates. The agent was readily transmitted to mice, with a mean incubation period of 408 days in the RIII strain. Because the incubation period was related to the titre of the inoculum, it is not a reliable characteristic of strain type on primary isolation. Consistent neuropathological changes associated with infection by the BSE agent in RIII and C57Bl mice included focal vacuolation in the dorsal cochlear nuclei, vacuolation of the granule cell layer of the cerebellum, absence of lesions in the hippocampus and in the molecular layer of the cerebellum, and a fine particulate distribution of disease-specific PrP (demonstrated immunohistochemically), with few or no amyloid plaques. These features, together with the conventional lesion profile, will be of use in distinguishing the agents of BSE and scrapie in sheep.

Animals↗

Comparability of the external vs internal location of radiation in inhibiting neointimal hyperplasia.

PURPOSE: One of the most controversial issues in utilizing radiation to inhibit restenosis is the importance of the location of the radiation source. The experimental results from using external forms of radiation have been contradictory and conflicting. In this study, we undertook to externally place a brachytherapy catheter source and to determine if a dose-response effect could be observed, as has been demonstrated with endovascular locations. MATERIALS AND METHODS: Neointimal hyperplasia was created in a rat carotid artery model by a balloon catheter technique. Immediately following injury, treatment groups received irradiation via an externally located high-dose rate (HDR) 192Ir brachytherapy catheter. This system allows for a more uniform dose delivery compared with endovascular radiation sources. Radiation was delivered to a 2-cm length of the injured vessel at doses of 5, 10, or 15 Gy and the animals were sacrificed at various time points following treatment (24 h to 6 months). Serial sections of tissue were stained immunohistochemically with primary antibodies for CD11b, platelet-derived growth factor (PDGF), and alpha-smooth muscle actin. RESULTS: Radiation doses of 5, 10, and 15 Gy inhibited the appearance of neointimal hyperplasia in a dose- and time-dependent manner. That is, doses of 5-15 Gy allowed for varying degrees of neointimal hyperplasia at 3 weeks posttreatment, with a greater resurgence of monocyte/macrophage activity at 5 Gy than at 10 or 15 Gy, where an absence of macrophage activity and PDGF expression was noted. From 2 to 6 months, the 10 and 15 Gy doses were again more suppressive of neointimal hyperplasia than 5 Gy, and at 6 months posttreatment the doses were approximately 25% and 50% effective, respectively. CONCLUSIONS: The demonstrated effectiveness of external brachytherapy provides "proof of principle," that it is the radiation dose delivered to the arterial wall, and not the location of the source, which is critical to a successful outcome. Ablation of the resident monocyte/macrophage population (or prevention of their activation) occurs with low to moderate doses of irradiation, leading to the absence of a cytokine cascade as evi denced by a lack of PDGF expression. A favorable therapeutic ratio exists, therefore, for radiation treatment of the arterial vasculature to prevent neointimal hyperplasia postangioplasty.

Animals↗

Effectiveness of fractionated external beam radiation in the inhibition of vascular restenosis.

BACKGROUND: From the clinical oncologic experience, fractionation of the radiation dose offers a better therapeutic window, both with respect to effectiveness and unwanted side effects. Thus, we undertook a pilot study in a rodent model, using a single dose of 15 Gy compared with fractionation schedules of 5 or 10 daily applications of 3 Gy. MATERIALS AND METHODS: Using a previously described rat angioplasty model, animals were randomly assigned to one of four groups: unilateral balloon injury, sham irradiation; unilateral balloon injury, bilateral 15 Gy single dose irradiation; unilateral balloon injury, bilateral 3 Gy x 5 daily fractions; or unilateral balloon injury, bilateral 3 Gy x 10 daily fractions. RESULTS AND CONCLUSIONS: All three radiation groups demonstrated a clear inhibition of neointimal hyperplasia. We therefore offer evidence for the effectiveness of fractionated radiation as a means to inhibit vascular restenosis in a rat carotid model. However, the 3 Gy x 5 schedule was less effective than either the 3 Gy x 10 schedule or the 15 Gy single dose. This study must be repeated using longer time points to provide proof of principle.

Animals↗

Hidden from view: violent deaths among pregnant women in the District of Columbia, 1988-1996.

OBJECTIVE: Maternal mortality is underreported in the United States in part because traumatic deaths are not included in nationally reported maternal mortality ratios. The overall study goal was to compare women whose deaths had been reported to and investigated by a medical examiner and who had evidence of pregnancy to women without evidence of pregnancy in terms of socio-demographic information, toxicology results, and manner and cause of death. A secondary goal was to compare the pregnancy status and gestational age of women with evidence of pregnancy at the time of death in relation to the manner of death, with particular focus on women who died as a result of violent death. METHODOLOGY: Autopsy charts from 1988-1996 for 651 women aged 15 to 50 from the District of Columbia Office of the Chief Medical Examiner whose autopsies included examination of the uterus were reviewed. Medical examiners' classification of manner and specific causes of death were used as the main outcome measures. Overall, the sample reflected demographic characteristics of women of childbearing age in the District of Columbia, with 82% black, 74.6% unmarried, and 46.5% aged 20 to 34. RESULTS: Among the 651 autopsy charts evaluated, 30 (4.6%) documented evidence of pregnancy; 43.3% of the women who died due to homicide with evidence of pregnancy were not included in the 21 pregnancy-related deaths officially reported by the District of Columbia State Center for Health Statistics during the study period, and therefore, were also not included in national maternal mortality ratios. Although not statistically significant, 11% more homicides occurred among women with evidence of pregnancy as compared to non-pregnant women. Pregnant women who died a violent death were significantly more likely than non-pregnant women to have died due to gunshot trauma. A significant proportion of pregnant women were < 21 weeks gestation at the time of their death. Additionally, women in this sample with evidence of pregnancy were over 3 times more likely to have been teenagers compared to non-pregnant women. CONCLUSION: Medical examiner autopsy records identify violent pregnancy-associated deaths, many of which occur early in pregnancy and are missed by other enhanced case-finding techniques that require a record of a birth or fetal death. These deaths are usually excluded from reported maternal mortality ratios. Few studies have evaluated the prevalence of homicide in women of childbearing age, yet understanding the extent of less commonly associated causes of death during pregnancy such as homicide, may lead to improved identification of preventable problems that contribute to maternal morbidity and mortality. This study, which sheds new light on the identifying and reporting of maternal mortality, and specifically on homicide as a form of violence toward pregnant women, should be of particular interest for all women's health providers, as well as public health professionals, researchers, and advocates who are interested in the design, development, and evaluation of prevention programs, especially those directed toward preventable problems such as domestic violence.

Adult↗

Adult gender identity disorder can remit.

A 4-year remission in a case of gender identity disorder (GID in DSM-IV, previously termed transsexualism) plus obsessive-compulsive disorder (OCD) prompted a search for further similar cases. Reports were reviewed for apparent remissions in adult GID. GID and paraphilias may wax and wane. This fluctuation can be in tandem with that of comorbid psychopathology or in response to sexual and other life events. Remission has been documented at up to 10 years. If evaluated over many years, GIDs and paraphilias can be less fixed than is often thought. The frequency of permanent remission may be underestimated, as such subjects may not consult clinicians. Implications for the clinician are that such subjects require a long trial period of cross-gender living prior to any surgical interventions.

Adult↗

A fast track to zero nuclear weapons: the Middle Powers Initiative and the New Agenda Coalition.

The Middle Powers Initiative is a network of international citizen organizations working to encourage the nuclear weapon states and their influential allies to move rapidly to eliminate nuclear weapons via practical steps including a Nuclear Weapons Convention. The New Agenda Coalition is a group of middle-ranking nations whose governments have also called for the early elimination of nuclear weapons via similar steps. The work of MPI and NAC at the United Nations and elsewhere is described, and their impact on NATO nuclear weapons policy discussed.

Humans↗

Structure and function of ribosomal RNA.

A refined model has been developed for the folding of 16S rRNA in the 30S subunit, based on additional constraints obtained from new experimental approaches. One set of constraints comes from hydroxyl radical footprinting of each of the individual 30S ribosomal proteins, using free Fe(2+)-EDTA complex. A second approach uses localized hydroxyl radical cleavage from a single Fe2+ tethered to unique positions on the surface of single proteins in the 30S subunit. This has been carried out for one position on the surface of protein S4, two on S17, and three on S5. Nucleotides in 16S rRNA that are essential for P-site tRNA binding were identified by a modification interference strategy. Ribosomal subunits were partially inactivated by chemical modification at a low level. Active, partially modified subunits were separated from inactive ones by binding 3'-biotinderivatized tRNA to the 30S subunits and captured with streptavidin beads. Essential bases are those that are unmodified in the active population but modified in the total population. The four essential bases, G926, 2mG966, G1338, and G1401 are a subset of those that are protected from modification by P-site tRNA. They are all located in the cleft of our 30S subunit model. The rRNA neighborhood of the acceptor end of tRNA was probed by hydroxyl radical probing from Fe2+ tethered to the 5' end of tRNA via an EDTA linker. Cleavage was detected in domains IV, V, and VI of 23S rRNA, but not in 5S or 16S rRNA. The sites were all found to be near bases that were protected from modification by the CCA end of tRNA in earlier experiments, except for a set of E-site cleavages in domain IV and a set of A-site cleavages in the alpha-sarcin loop of domain VI. In vitro genetics was used to demonstrate a base-pairing interaction between tRNA and 23S rRNA. Mutations were introduced at positions C74 and C75 of tRNA and positions 2252 and 2253 of 23S rRNA. Interaction of the CCA end of tRNA with mutant ribosomes was tested using chemical probing in conjunction with allele-specific primer extension. The interaction occurred only when there was a Watson-Crick pairing relationship between positions 74 of tRNA and 2252 of 23S rRNA. Using a novel chimeric in vitro reconstitution method, it was shown that the peptidyl transferase reaction depends on this same Watson-Crick base pair.

Models, Biological↗

Cricopharyngeal myotomy: management of cervical dysphagia.

Cricopharyngeal myotomy has gained widespread acceptance as surgical treatment for various forms of cervical dysphagia. The case records of 33 patients who underwent cricopharyngeal myotomy for dysphagia originating from varying underlying diseases are reviewed. The majority of these patients were able to resume oral feeding following myotomy. Analysis of preoperative pharyngoesophageal manometry and contrast radiography identified diagnostic criteria for appropriate case selection.

Adult↗

Degradation of N-nitrosodimethylamine (NDMA) in landscape soils.

N-nitrosodimethylamine (NDMA), a potential carcinogen, was commonly found in treated wastewater as a by-product of chlorination. As treated water is increasingly used for landscape irrigation, there is an imperative need to understand the leaching risk for NDMA in landscape soils. In this study, adsorption and incubation experiments were conducted using landscape soils planted with turfgrass, ground cover, and trees. Adsorption of NDMA was negligibly weak (K(d) < 1) in all soils, indicating that NDMA has a high potential for moving with percolating water in these soils. Degradation of NDMA occurred at different rates among these soils. At 21 degrees C, the half-life (t(1/2)) of NDMA was 4.1 d for the ground cover soil, 5.6 d for the turfgrass soil, and 22.5 d for the tree soil. The persistence was substantially prolonged after autoclaving or when incubated at 10 degrees C. The rate of degradation was not significantly affected by the initial NDMA concentration or addition of organic and inorganic nutrient sources. The relative persistence was inversely correlated with soil organic matter content, soil microbial biomass, and soil dehydrogenase activity, suggesting the importance of microorganisms in NDMA degradation in these soils. These results suggest that the behavior of NDMA depends closely on the vegetation cover in a landscape system, and prolonged persistence and increased leaching may be expected in soils with sparse vegetation due to low organic matter content and limited microbial activity.

Adsorption↗