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Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 307 records · Page 17Linked to original sources

A novel unstable mouse VNTR family expanded from SINE B1 elements.

Human hypervariable minisatellites provide highly informative loci for analyzing processes of tandem repeat turnover, but little is known about mechanisms of instability in other species. We have therefore screened the mouse genome for analogous VNTR loci. One of the probes we isolated, MMS10, detects a highly variable rodent-specific family of multiple loci derived by expansion of a common GGCAGA repeat unit from within a subset of B1 short interspersed elements. The mean germline mutation rate for loci detected by MMS10 was estimated at 1.7% per offspring band, though analysis of individual loci showed substantial variation in germinal instability apparently related to repeat array size. This MMS10 family of expanded hexanucleotide repeat loci provides a novel resource for investigating mechanisms of tandem repeat turnover in the mouse and an efficient means for monitoring germline mutations induced by external agents such as ionizing radiation.

Animals↗

Phakic patients with cystoid macular edema, retinal periphlebitis, and vitreous inflammation.

OBJECTIVE: To characterize a group of phakic patients with idiopathic intermediate uveitis as defined by vitritis, cystoid macular edema, and retinal periphlebitis. DESIGN: Cross-sectional study. PARTICIPANTS: Nineteen phakic patients (35 eyes) with vitreous inflammation, cystoid macular edema, and/or retinal periphlebitis of unknown cause. INTERVENTION: None. MAIN OUTCOME MEASURES: Best-corrected final visual acuities, standardized clinical examinations, photographic and fluorescein angiographic evaluations, and class I and II HLA analysis on all 19 patients. RESULTS: Fifteen of the 19 patients were women. The mean age was 38 years, the mean follow-up was 104 months, and the mean duration of symptoms was 154 months. All 35 affected eyes had significant vitritis; 21 eyes (60%) had cystoid macular edema, 21 eyes (60%) had retinal periphlebitis. The median initial visual acuity was 20/30. The median final visual acuity was 20/20 with 32 (91%) of 35 eyes having 20/40 or better visual acuity at the final visit. No patient developed "snow-banks" or evidence of systemic disease, including multiple sclerosis or sarcoidosis, during the follow-up period. There were no statistically significant HLA associations in these patients compared with controls from another study from Iowa, but the Iowa phakic patients with cystoid macular edema did differ from the Iowa patients with pars-planitis at loci HLA-B8, HLA-B51, and HLA-DR2. CONCLUSIONS: We describe a disease entity of idiopathic intermediate uveitis that affects primarily young to middle-aged women and usually causes bilateral vitritis, cystoid macular edema, and retinal periphlebitis. Most patients retained good vision over a prolonged follow-up period. Multiple sequential examinations and HLA associations suggest that these conditions are distinct from other syndromes of intermediate uveitis, particularly parsplanitis.

Adolescent↗

Chromosome 3-linked frontotemporal dementia.

Frontotemporal dementia accounts for a significant minority of all cases of presenile dementia. Many pedigrees have been described in which frontotemporal dementia is inherited as an autosomal dominant trait. Frontotemporal dementia is genetically heterogeneous with loci identified on chromosome 17 and chromosome 3. Clinical, pathological and genetic findings are described in a large Danish family in which the disease gene lies in the pericentromeric region of chromosome 3.

Age of Onset↗

A sequential randomised controlled trial comparing a dry visco-elastic polymer pad and standard operating table mattress in the prevention of post-operative pressure sores.

Four hundred and forty-six general, vascular and gynaecological surgical patients were recruited to a two centre, double triangular sequential randomised controlled trial to compare the post-operative pressure sore incidence in patients positioned on the standard operating table mattress with those positioned on the dry visco-elastic polymer pad (Action Products Inc.). Two hundred and twenty two patients were randomised to the experimental group and 224 to the standard mattress. The main endpoint failure rate (a pressure sore) was found to be 11% (22/205) for patients allocated to the dry visco-elastic polymer pad and 20% (43/211) for patients allocated to the standard operating table mattress. There was a significant reduction in the odds of developing a pressure sore on the dry visco-elastic polymer pad as compared to the standard, [symbol see text] = 0.46 with 95% confidence interval of (0.26, 0.82), P = 0.010. The adjusted point estimates of the probability of developing a pressure sore on the dry visco-elastic polymer pad and the standard operating table mattress were 0.11 and 0.21 respectively.

Aged↗

A longitudinal analysis of risk factors for child maltreatment: findings of a 17-year prospective study of officially recorded and self-reported child abuse and neglect.

OBJECTIVE: To identify demographic, family, parent, and child factors prospectively associated with risk for child abuse and neglect among families in the community, using data on child maltreatment obtained from both official records and youth self-reports. METHOD: Surveys assessing demographic variables, family relationships, parental behavior, and characteristics of parents and children were administered to a representative sample of 644 families in upstate New York on four occasions between 1975 and 1992. Data on child abuse and neglect were obtained from New York State records and retrospective self-report instruments administered when youths were > or = 18 years old. RESULTS: Logistic regression analyses indicated that different patterns of risk factors predicted the occurrence of physical abuse, sexual abuse, and neglect, although maternal youth and maternal sociopathy predicted the occurrence of all three forms of child maltreatment. In addition, the prevalence of child abuse or neglect increased from 3% when no risk factors were present to 24% when > or = 4 risk factors were present. State records and self-reports of child maltreatment did not correspond in most cases when maltreatment was reported through at least one data source, underlining the importance of obtaining data from both official records and self-reports. CONCLUSIONS: Assessment of a number of risk factors may permit health professionals to identify parents and children who are at high risk for child maltreatment, facilitating appropriate implementation of prevention and treatment interventions.

Child↗

Cytokines and the protective host immune response to Chlamydia psittaci.

The immunobiology of enzootic abortion of ewes (EAE) is incompletely understood. The causative agent is Chlamydia psittaci, which infects many ruminant species and has zoonotic potential. The organism can survive in the ovine host for many months without causing clinical symptoms but does not generate a sterile immunity during this time. It has been postulated that the organism persists in the host entering at a latent phase, possibly mediated by host cytokine production. The effects of cytokines on chlamydial multiplication vary between host species, between different cell types within those species and also vary between chlamydial species and strains. The multiplication of the EAE strain of C. psittaci in ovine ST-6 cells can be restricted by interferon-gamma (IFN-gamma) but not with comparable concentrations of IFN-alpha. Altering the nutrient composition of the cultures by addition of tryptophan partially reverses the antichlamydial effects of the IFN-gamma. This offers a potential mechanism by which C. psittaci can persist in sheep. The implications of these observations for the pathogenesis of EAE are discussed.

Abortion, Veterinary↗

Patterns of visual field progression in patients with retinitis pigmentosa.

OBJECTIVE: The purpose of the study was to determine whether distinct patterns of visual field progression are present in patients with retinitis pigmentosa (RP) and to evaluate the correlation between these patterns, if present, and different genetic subtypes of RP. DESIGN: A retrospective analysis of patterns of visual field progression in RP was performed. PARTICIPANTS: Visual fields of 162 patients with RP, including 55 with type 2 Usher syndrome, who had at least 3 Goldmann visual field examinations during a period of at least 3 years were reviewed. MAIN OUTCOME MEASURES: Goldmann visual fields. RESULTS: Visual fields of 86 patients could be classified into one of three specific patterns of visual field progression. Pattern I included those patients with a progressive concentric loss of visual fields; pattern II included those with visual field loss that began superiorly and subsequently developed an arcuate scotoma that progressed either from the nasal (IIA) or the temporal (IIB and IIC) side; and pattern III included patients whose visual field loss was characterized initially by a complete or incomplete midperipheral "ring scotoma" that broke through into the periphery. The end stage of all these patterns was a residual central visual field, sometimes also associated with a small peripheral island. In 53 of the 162 patients, the pattern of visual field loss could not be categorized because of an advanced stage of field loss at the time of the initial examination. CONCLUSIONS: Distinctive patterns of visual field progression can be observed in patients with retinitis pigmentosa and type 2 Usher syndrome. There were no intrafamilial variations in the pattern of visual field loss in our data on 24 patients from 11 families. Within certain genetic subtypes, there was a predilection for a preponderance of a specific pattern of visual field progression. Future studies may be able to correlate these patterns of visual field loss with different genetic mutations. A greater understanding as to why certain patterns of field loss exist could potentially provide greater insight into the various pathogenetic mechanism(s) by which photoreceptor cells degenerate in this group of patients.

Deafness↗

Valuing temporary and chronic health states associated with breast screening.

The aim of this study was to derive quality of life values for the four key breast screening outcomes (true negative, false positive, true positive and false negative), including the quality of life effects of the screening and treatment processes. In doing so, methodological issues in health status measurement were explored, in particular the valuation of temporary health states. The true negative and false positive descriptions were temporary health states, lasting for short term durations (12 months) and the true positive and false negative outcomes were chronic health states lasting for long term durations (rest of life). Descriptions of breast screening outcomes were valued using the time trade-off technique and the visual analogue scale. Paired comparisons between TTO values for states with the same duration found a difference between the true negative and the false positive time trade-off values but no difference for true positive and false negative descriptions. The TTO values for the false positive were low. The study highlights several important methodological issues such as the use of the two stage procedure for valuing temporary health states, the impact of duration on values, the impact of anchor points, and the importance of qualitative analysis of respondents values. Further empirical testing of all these issues is recommended.

Adult↗

Utility of serum progesterone and prolactin analysis for assessing reproductive status in the Asian elephant (Elephas maximus).

Concentrations of serum progesterone and prolactin were assessed during the perioestrous period and throughout gestation in the Asian elephant (Elephas maximus) as a means of generating information of potential use to managers. In > 95% of perioestrous periods (n=35), behavioural oestrus (as determined by bull interest, mounting and/or breeding) coincided with the onset of increased serum progesterone concentrations at the beginning of the luteal phase and continued through Day 7 (Day 1 = first significant serum progesterone rise). Within individuals, 1- to 2-day transient decreases (P < 0.05) in serum progesterone occurred between Days 2 and 9. Notably, no sexual behaviour was observed in any female after this transient fall in progesterone. Prolactin concentrations fluctuated randomly throughout the perioestrous period, with no clear pattern. During the study, four females conceived (one conceived twice), and two delivered three viable offspring. Serum progesterone was elevated above baseline throughout gestation, and then declined precipitously 2-3 days before parturition. Serum prolactin concentrations were significantly elevated above baseline (P < 0.05) after 5-6 months of gestation and remained high until after parturition. This study confirms that serum progesterone and prolactin analyses are useful tools for monitoring the reproductive status of Asian elephant females. Specifically, the transition from low to high progesterone secretion during the late interluteal/early luteal phase is predictive of oestrus and can be used to coordinate breeding efforts. Pregnancy can be confirmed by elevated serum prolactin after 6 months postbreeding, whereas the late gestational decrease in progesterone is predictive of impending parturition.

Animals↗

Relaxation therapy in Tourette syndrome: a pilot study.

To evaluate the feasibility and efficacy of behavioral relaxation therapy as treatment for Tourette syndrome, 23 patients were recruited from a university-based pediatric Tourette syndrome referral clinic. Individuals were randomized and stratified according to initial tic severity and the presence of attention-deficit hyperactivity disorder into either relaxation therapy or a minimal therapy (control) group. Sixteen patients, mean age 11.8 years (S.D. 2.8 years), completed the 3-month study, which included weekly, hour-long, individual training sessions for 6 weeks. Individuals (n = 7) in the relaxation therapy group demonstrated a significantly increased ability to relax, compared with the minimal therapy (awareness and quiet time training) group. At 6 weeks, tic findings, based on five established tic severity scales, revealed greater improvement in the relaxation treatment group, but values failed to reach statistical significance. No difference between therapy groups was apparent at the 3-month evaluation. The acquired ability to relax did not significantly affect behavioral measures on the Child Behavioral Checklist. On the basis of this pilot study, relaxation therapy appears to have a limited role in the treatment of tics in Tourette syndrome.

Adolescent↗

Cell binding properties of collagen type XIV for human hematopoietic cells.

Collagen XIV, which belongs to the subclass of fibril-associated collagens with interrupted triple helices (FACITs), is a homotrimeric molecule consisting of three alpha 1 (XIV) chains. Collagen type XIV is strongly expressed in the native human bone marrow, as shown by immunofluorescence staining and immunoblotting with an affinity-purified antibody. Hematopoietic cell lines of myeloid (KG1a, U937, K562) and lymphoid (U266, IM-9) origin were able to attach firmly to purified human collagen XIV preparations. Attachment of these cells was shown to be concentration-dependent. However, other hematopoietic cell lines tested were unable to adhere to collagen XIV, indicating restriction of this cellular interaction. The cellular receptors involved in cell binding to collagen type XIV are probably membrane-bound heparansulfate proteoglycans, since only the the addition of heparin inhibited attachment of the hematopoietic cells to collagen XIV in a concentration-dependent manner. Antibodies against the beta 1-integrin subunit could not interfere with binding to collagen type XIV. Using purified fragments of collagen XIV, it could be demonstrated that at least two different heparin-sensitive adhesion sites are present in the N-terminal globular domain and in the triple-helical domain. These data indicate that collagen XIV represents another collagen type expressed in human bone marrow with strong cell binding properties for defined populations of hematopoietic cells.

Bone Marrow Cells↗

Xenotransplantation and the risk of retroviral zoonosis.

It is hypothesized that xenotransplantation could facilitate the emergence of new human pathogens. Retroviruses might pose the greatest public health risk because of the possibility of undetected transmission within a population. Evidence from naturally occurring retroviral zoonoses and cross-species infections by animal retroviruses provides a basis for reasoned speculation on the risks posed by xenotransplantation.

Animals↗

The effect of cross-linking on the in vivo disintegration of hard gelatin capsules.

PURPOSE: To evaluate if the cross-linking of gelatin affects in vivo capsule disintegration. METHODS: Scintigraphic investigation in nine healthy volunteers to provide for a real time visualisation of capsule disintegration. RESULTS: The moderately stressed capsules failed the USP dissolution specification for acetaminophen capsule when tested in water and conventional SGF but passed with the addition of pepsin. Moderately stressed capsules started to disintegrate at 10 +/- 6 minutes (range 6 to 24 minutes) compared to 8 +/- 2 minutes (range 5 to 11 minutes) for the unstressed capsule. CONCLUSIONS: The results of the study clearly demonstrate that with the incisive technique of gamma scintigraphy there are no differences in the in vivo disintegration properties of moderately stressed and unstressed capsules.

Acetaminophen↗

Selecting a decision model for economic evaluation: a case study and review.

The increased use of modelling techniques as a methodological tool in the economic evaluation of health care technologies has, in the main, been limited to two approaches--decision trees and Markov chain models. The former are suited to modelling simple scenarios that occur over a short time period, whilst Markov chain models allow longer time periods to be modelled, in continuous time, where the timing of an event is uncertain. In the context of economic evaluation, a less well developed technique is discrete event simulation, which may allow even greater flexibility. Taking the economic evaluation of adjuvant therapies for breast cancer as an illustrative example, the process of building a decision tree, a Markov chain model, and a discrete event simulation model are described. The potential benefits and problems of each approach are discussed. The suitability of the modelling techniques to economic evaluations of health care programmes in general is then discussed. This section aims to illustrate the areas in which the alternative modelling methods may be most appropriately employed.

Adult↗

Identification of a human population infected with simian foamy viruses.

Studying the transmission of simian retroviruses to humans can help define the importance of these infections to public health. We identified a substantial prevalence (4/231, 1.8%) of infection with simian foamy viruses (SFV) among humans occupationally exposed to nonhuman primates. Evidence of SFV infection included seropositivity, proviral DNA detection and isolation of foamy virus. The infecting SFV originated from an African green monkey (one person) and baboons (three people). These infections have not as yet resulted in either disease or sexual transmission, and may represent benign endpoint infections.

Animals↗

Lymphopain, a cytotoxic T and natural killer cell-associated cysteine proteinase.

Through differential screening of established human leukaemia cell lines, we have identified and molecularly cloned lymphopain, a novel cysteine proteinase of the papain family. Lymphopain exhibits a remarkably restricted cellular pattern of expression, being predominantly expressed in cytotoxic T-lymphocytes and natural killer cells. The human lymphopain locus maps to chromosome 11q13, encodes a polypeptide of 376 amino acids and is conserved in the mouse. Both human and murine forms appear more closely related to protozoan papain-like enzymes than to other mammalian members of the papain family. The cellular distribution of lymphopain expression, together with the functional demonstration of lymphopain-associated proteinase activity in vitro, is suggestive of a role for lymphopain in immune cell-mediated, cell killing.

Amino Acid Sequence↗