Meaningful connections in medicine.
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Community Medicine↗
Biomedical subjects
K Brown
Publications and source records attributed to K Brown.
Alteration in H chain V region affects complement activation by chimeric antibodies.
Chimeric antibodies to the synthetic polypeptide (Tyr, Glu)-Ala-Lys ((T,G)-A-L) were used to examine C activation by human IgG1. Two IgG1 antibodies, which contained mouse L chains and H chains with mouse V domains and human C domains, differed only in their VH domain. Ag binding and C activation by these antibodies were analyzed by ELISA. When limiting amounts of Ag were used in the assays, the antibodies required different quantities of Ag for optimal binding, suggesting that the antibodies bind to different epitopes on the (T,G)-A-L molecule. However, when competitive inhibition assays were performed with an optimal concentration of Ag, there were no differences in relative binding affinities for (T,G)-A-L or dissociation characteristics of the antibodies. C activation was examined at optimal Ag concentration to ensure equivalent binding of two IgG1 antibodies to Ag. After combination with immobilized Ag, these two antibodies bearing different V regions exhibited marked differences in the binding of C components C1q and C3d. When present in equal amounts in the assay, antibody 10B activated C and bound more C1q and C3d than antibody B11. These results indicate that V region differences can affect C activation by IgG.
Amino Acid Sequence↗
Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter.
The promoter region of the suprabasal keratin 10 gene has been used to direct expression of a mutant human Harvey-ras oncogene to the differentiating cells of the mouse epidermis. Transgenic animals develop hyperkeratosis of the skin and forestomach--the two sites known to express high levels of the keratin 10 polypeptide in vivo. Papillomas subsequently develop on the skin surface, initially at sites subject to biting or scratching such as the base of the tail or behind the ears. The results suggest that the "second event" involved in tumor development in these transgenic animals is the local induction of a mild wounding stimulus. Furthermore, because the H-ras transgene is expressed in suprabasal cells, it appears that cells which have left the stem cell compartment can be induced to form at least benign tumors in vivo.
Animals↗
Prevalence of psychological distress in Irish female adolescents.
Some female adolescents (N = 132) attending two inner city Dublin schools completed the Youth Self Report Questionnaire (YSRQ). Of this group 15.4 per cent obtained a Total Problem Score in the clinical range. A higher proportion, 23 per cent, obtained a score in the clinical range on one or more problem subscales of the YSRQ. No one scored abnormally on the Social or Competence Scales. A number of interesting and thought provoking responses to individual questions were obtained. The possible clinical relevance of these findings and implications for future planning in schools are discussed.
Adolescent↗
The sixth stool guaiac test: $47 million that never was.
In a 1975 paper, Neuhauser and Lewicki analysed a colorectal cancer screening policy approved by the American Cancer Society. Their analysis yielded an incremental cost per case detected in excess of $47 million. This vivid demonstration of the impact of marginal analysis is frequently cited by health economists and is often used for pedagogic purposes. The analysis is incorrect because of two fundamental errors. We have reanalysed the protocol in two stages. After correction for these errors, the $47 million disappears, the marginal cost is quite modest and the policy appears to be defensible on economic grounds.
American Cancer Society↗
Ontogeny of the neuronal intermediate filament protein, peripherin, in the mouse embryo.
The expression of peripherin, a type III neuron-specific intermediate filament protein, and the middle neurofilament subunit were studied in the mouse embryo using immunofluorescence staining. The earliest staining for both proteins is seen at embryonic day 9 in the myelencephalon, initially as fiber staining followed by cell body staining in the developing facial and acoustic nuclei. As the embryo develops, there is rostral as well as caudal extension of peripherin and staining is seen in the trigeminal ganglia, nerve fibers and in the enteric nervous system. As the spinal cord forms there is anti-peripherin staining in developing motoneurons of the anterior horns while little cell body staining is seen for the middle neurofilament subunit. Both antibodies stain the developing dorsal root and its entry zone, but peripherin is found in the secondary sensory and commissural fibers while the middle neurofilament subunit is not. While both proteins are found in the neurons of the dorsal root ganglia, their distribution varies. The larger peripheral cells of the ganglia contain both proteins while the smaller more central cells, constituting over 60% of the cells in the ganglia, contain only peripherin. A similar picture is found in the sympathetic ganglia where there are cells which contain peripherin. middle neurofilament subunit or both, but where the majority of the neurons have only peripherin in their cell bodies. Peripherin is not found in the developing retina or in the adrenal medulla. Peripherin is also completely absent from cell bodies in the cerebral and cerebellar cortices. These results indicate that peripherin is found in development only in regions in which it is found in the adult. It can either co-exist with neurofilaments in the same neuron or the two may be independently expressed.
Animals↗
Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumor progression.
A number of mouse skin tumors initiated by the carcinogens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methylnitrosourea (MNU), 3-methylcholanthrene (MCA), and 7,12-dimethylbenz[a]anthracene (DMBA) have been shown to contain activated Ha-ras genes. In each case, the point mutations responsible for activation have been characterized. Results presented demonstrate the carcinogen-specific nature of these ras mutations. For each initiating agent, a distinct spectrum of mutations is observed. Most importantly, the distribution of ras gene mutations is found to differ between benign papillomas and carcinomas, suggesting that molecular events occurring at the time of initiation influence the probability with which papillomas progress to malignancy. This study provides molecular evidence in support of the existence of subsets of papillomas with differing progression frequencies. Thus, the alkylating agents MNNG and MNU induced exclusively G ---- A transitions at codon 12, with this mutation being found predominantly in papillomas. MCA initiation produced both codon 13 G ---- T and codon 61 A ---- T transversions in papillomas; only the G ---- T mutation, however, was found in carcinomas. These findings provide strong evidence that the mutational activation of Ha-ras occurs as a result of the initiation process and that the nature of the initiating event can affect the probability of progression to malignancy.
9,10-Dimethyl-1,2-benzanthracene↗
Biodynamics of the ankle in spastic children--effect of chronic stretching of the calf musculature.
The biodynamics of the feet of spastic children have been studied by estimating the resonant frequency using a printed motor to supply rhythmic torques. Changes induced when the muscles have been stretched by casting for four weeks are trivial or absent. The position of the feet, however, after the procedure became more nearly normal.
Adolescent↗
Lymphangiomyomatosis: CT, chest radiographic, and functional correlations.
Eight patients with the diagnosis of lymphangiomyomatosis were evaluated with computed tomography (CT), chest radiography, and pulmonary function tests to determine the relationship between the extent of disease seen on imaging studies and functional status. Chest radiographic assessment included the subjective determination of disease extent and measurements of lung length and the arc of the right hemidiaphragm. Disease extent on CT scans was scored as a percentage of lung that was abnormal on the basis of visual assessment of the degree of cystic replacement of the lung parenchyma. Significant correlations were observed between CT scores and percentages of predicted forced expiratory volume in 1 second/forced vital capacity (r = -.92, P less than .002) and diffusing capacity of the lungs for carbon monoxide (r = -.80, P less than .017). No significant correlations were observed between subjective chest radiographic scores and pulmonary function tests, although measurements of lung length and percentage of predicted total lung capacity were correlated (r = .76, P less than .045). CT was more accurate than chest radiography in defining the presence and extent of parenchymal cysts and provided for greater morphologic-physiologic correlation. CT, particularly high-resolution CT, may be useful in the diagnosis and longitudinal evaluation of patients with this disease and may be more sensitive than pulmonary function tests in the early stages of lung damage.
Adult↗
The effect of retinoic acid on growth and proto-oncogene expression in hamster tracheal epithelial cells.
Retinoic acid (RA) has been shown to be required for the maintenance of epithelial differentiation. Vitamin A deficiency in hamsters induces the tracheal epithelial cells to undergo squamous metaplasia. Reversing the vitamin deficiency restores the tracheal epithelial cells to their normal morphology and function. Using a hamster tracheal epithelial (HTE) cell culture system which undergoes differentiation to predominantly secretory cells in vitro, we found that RA can convert flat, squamous-like cells to compact, cuboidal-like cells, and that it stimulated cell proliferation. The mitogenic response to RA was maximal at 10(-7) M and required at least 48 h of treatment to observe the effect. RNA levels of growth-related genes during the growth and differentiation phases of primary HTE cultures were examined by Northern analysis. RA maintained a high level of c-myc RNA expression in preconfluent cultures, whereas untreated cells had low amounts of c-myc RNA. Expression of RNA for the replication-dependent histone 3.2 followed a similar pattern, i.e., its level was high in retinoid-treated versus control preconfluent cultures. In confluent (fully differentiated) HTE cell cultures, both retinoid-treated and control cells had low RNA levels of c-myc and histone 3.2. c-fos RNA levels were undetectable in either control or treated cells at any stage during primary culture. The RNA level of c-Ha-ras was very low in both control and treated cultures and did not vary with the state of growth or differentiation, except that when RA-treated cultures reached confluence, no c-Ha-ras RNA was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Current use of imaging in the evaluation of primary mediastinal masses.
A wide variety of lesions occur in the mediastinum in patients of every age. Twenty five to 50 percent of these primary mediastinal masses may be malignant, making early diagnosis and therapy crucial. Since most arise from normal structures in the region, localization of lesions to compartments of the mediastinum may assist in diagnosis. This article reviews imaging techniques for lesions originating in the mediastinum.
Arteriovenous Malformations↗
Alcohol-predictive cues enhance tolerance to and precipitate "craving" for alcohol in social drinkers.
This study attempts to show that tolerance to alcohol is in large part a "learned" response, precipitated by contextual cues predictive of the unconditional drug effect. It also aims to show that the contextual cues integral to such "environment-dependent" tolerance function to increase motivational desire to drink alcohol. Male students (N = 40), drinking on average 10-20 units of alcohol per week, were randomly assigned to one of four groups. Two groups ingested 1.2ml/kg alcohol: one (AL-EXPT) with exteroceptive contextual cues typically associated with alcohol use, and the other (AL-UNEXPT) in a context not normally associated with alcohol. A third group (placebo) believed that they were drinking alcohol but, in fact, consumed a nonalcoholic beverage in the alcohol-expected context. The fourth group drank juice in the alcohol-unexpected context. As predicted, tolerance to the deleterious effects of alcohol on cognition and motor-performance, and subjective desire to consume alcohol, were influenced by the alcohol-predictive contextual cues. A physiological index (pulse rate) also tended to confirm that these cues elicited a conditioned compensatory response to alcohol. The implications of these findings for tolerance to and motivation to drink alcohol in a nonpathological population are discussed.
Adult↗
Longitudinal characteristics of hospital use before and after alcoholism treatment.
The frequency of inpatient hospital care for three years before and three years after alcoholism treatment was evaluated for a group of 255 patients of predominantly lower socioeconomic status treated for alcoholism at a rural midwestern medical center in 1983. Subjects were interviewed while in treatment to obtain information regarding alcoholism history and demographics. Hospital care was ascertained from an electronic data file of discharges from 172 acute care hospitals throughout the United States and Puerto Rico. One-third of the sample was never hospitalized for an alcohol-related condition in the years prior to or after alcoholism treatment, and 23% of the sample experienced no hospitalizations at all other than the treatment episode when interviewed. The majority of hospital stays before and after treatment were attributed to alcohol abuse. The frequency and total hospital length of stay for alcohol-related admissions increased yearly before treatment, peaked in the year after treatment, and then declined, but not to earliest pretreatment levels. Subjects experienced significantly more hospitalizations and length of stay after alcoholism treatment than before when comparing both the two three-year periods and the immediate 12 months before and after treatment. More frequent hospital care was also significantly associated with higher levels of daily alcohol consumption and drinking duration but not with sociodemographic indicators.
Adult↗
Auditory psychomotor coordination and visual search performance.
In Experiments 1 and 2, the time to locate and identify a visual target (visual search performance in a two-alternative forced-choice paradigm) was measured as a function of the location of the target relative to the subject's initial line of gaze. In Experiment 1, tests were conducted within a 260 degree region on the horizontal plane at a fixed elevation (eye level). In Experiment 2, the position of the target was varied in both the horizontal (260 degrees) and the vertical (+/- 46 degrees from the initial line of gaze) planes. In both experiments, and for all locations tested, the time required to conduct a visual search was reduced substantially (175-1,200 msec) when a 10-Hz click train was presented from the same location as that occupied by the visual target. Significant differences in latencies were still evident when the visual target was located within 10 degrees of the initial line of gaze (central visual field). In Experiment 3, we examined head and eye movements that occur as subjects attempt to locate a sound source. Concurrent movements of the head and eyes are commonly encountered during auditorily directed search behavior. In over half of the trials, eyelid closures were apparent as the subjects attempted to orient themselves toward the sound source. The results from these experiments support the hypothesis that the auditory spatial channel has a significant role in regulating visual gaze.
Adult↗
P & T Committee perspectives: maintaining a successful formulary system in a private community hospital.
Institution of an effective formulary and P & T Committee is a difficult but critical task for many private hospitals. In this exclusive Hospital Formulary interview, Drs. Benner, Mykita, and Brown, members of Sutter Memorial Hospital's Pharmacy, Formulary, and Therapeutic Review Committee (their name for the P & T Committee) emphasize the need for a sound formulary system in order to survive the current changes in health care. Sutter Memorial is sophisticated in its delivery of healthcare services, which include advanced neonatology and state-of-the-art heart transplantation. Although good patient care remains the foremost concern, these committee members acknowledge that care must be affordable as well as therapeutically sound. Key to their committee's success is the cooperative effort among the pharmacy, nursing, and medical staff. They foresee the issue of rational therapeutics as a major challenge in the 1990s.
California↗
New 18F tracers for the investigation of brain functions.
Advances in the synthetic methodology of radiofluorination have increased the number of clinically useful 18F labeled tracers for positron emission tomography of the brain. It is now possible to measure in vivo with 18F tracers regional cerebral blood flow (18F-fluoromethane), dopamine metabolism (6-18F-fluoro-L-dopa) and dopamine D-2 receptor density (N-18F-fluoroethylspiperone). At present 18F tracers are being developed that will, in the near future, make accessible to investigation cerebral serotonin metabolism, serotonin receptor density, melatonin receptor density, activity of L-aromatic acid decarboxylase, and protein synthesis rate.
Brain↗
The interplay between ras oncogenes and tumor suppressor genes in experimental carcinogenesis.
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Animals↗
Time course of rabbit ocular inflammatory response and mediator release after intravitreal endotoxin.
An inflammatory response was elicited in the rabbit eye by intravitreal injection of endotoxin. The appearance in aqueous humor of selected metabolites of arachidonic acid metabolism at various times was correlated with the influx of protein and myeloperoxidase activity in the iris-ciliary body. After intravitreal injection of endotoxin, aqueous humor protein levels increased substantially within 2 hr. This aqueous humor protein increase occurred before a significant appearance of prostaglandin E2 (PGE2) in the aqueous humor. Myeloperoxidase activity in the iris-ciliary body, a measure of polymorphonuclear leukocyte (PMN) infiltration, showed little elevation until 6 hr after endotoxin injection and then increased rapidly through 24 hr. The appearance of the leukotriene B4 (LTB4) followed a similar time course: levels in the aqueous humor were partially elevated until 6 hr after endotoxin injection, when levels begin to rise rapidly. These findings are interpreted to demonstrate the dependence of PMN infiltration on the release and accumulation of LTB4; the initial breakdown of the blood-aqueous barrier and influx of protein appears to be independent of significant release of PGE2.
Animals↗