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Biomedical subjects

E Brown

Publications and source records attributed to E Brown.

At least 181 records · Page 10Linked to original sources

Effect of photodynamic therapy on RIF-1 tumor metabolism and blood flow examined by 31P and 2H NMR spectroscopy.

Photodynamic therapy utilizes the tumor localizing drug dihematoporphyrin ether and red laser light to produce both direct tumor cell destruction via damage to mitochondrial membranes, and also indirect cell kill via destruction of the tumor vasculature. As a first step towards examining the mechanistic relationship between metabolic and vascular effects of photodynamic therapy, murine RIF-1 tumors were treated with a subcurative treatment (500 J/cm2). Tumor metabolic status was monitored using in vivo 31P NMR before, during and after the treatment. The tumor blood flow immediately before and after treatment was measured by direct intratumor injection of D2O saline and observation of the tracer signal clearance from the tumor via 2H NMR. During the photodynamic therapy treatment, significant decreases were observed for the nucleoside triphosphate concentrations, tumor pH and tumor blood flow, while inorganic phosphate concentrations increased. Animals treated with laser light alone and those not given any treatment, demonstrated no significant changes in tumor metabolic status, tumor pH or tumor blood flow. Further studies are required to determine whether tumor blood flow or metabolic status is affected first.

Animals↗

Size constancy at birth: newborn infants' responses to retinal and real size.

Two experiments are described whose aim was to investigate whether perception of size at birth is determined solely by proximal (retinal) stimulation, or whether newborn babies have the ability to perceive an object's real size across changes in distance. In Experiment 1, preferential looking between pairs of stimuli which varied in real size and viewing distance was found to be solely determined by retinal size, suggesting that changes to proximal stimulation can have profound effects on newborns' looking behavior. However, in Experiment 2 newborns were desensitized to changes in distance (and retinal size) during familiarization trials, and subsequently strongly preferred a different sized object to the familiar one, suggesting that the real size had been perceived as constant across the familiarization trials. These results confirm Granrud's (1987) findings that size constancy is present at birth.

Attention↗

Time course of postischemic intracellular alkalosis reflects the duration of ischemia.

We investigated the long-term (up to 1 week) relationships between the duration of cerebral ischemia and postischemic energy metabolic profile, pH, and tissue edema in the rat. Ten rats each were subjected to 8 or 12 min of forebrain ischemia induced by bicarotid occlusion concurrent with systemic hypotension, and the results were compared with those of 10 sham-operated rat controls. In vivo 31P nuclear magnetic resonance spectroscopy was performed prior to ischemia and at intervals up to 168 h after ischemia. Cerebral edema (measured by specific gravity) was assessed prior to ischemia and at 24, 72, and 168 h after ischemia. The data revealed significant differences in the brain tissue pH profile over time between the ischemic groups (p less than 0.03). The 12-min ischemic animals exhibited brain tissue alkalosis (pH = 7.27 +/- 0.12) at 24 h compared with both sham (pH = 7.09 +/- 0.08) at 24 h and preischemic (pH = 7.06 +/- 0.04) pH values. The pH remained alkalotic (pH = 7.23 +/- 0.15) through the 48-h time period. In contrast, in the 8-min group, the onset of alkalosis was delayed until 48 h after ischemia (pH = 7.24 +/- 0.15), and pH remained alkalotic for only 24 h. No difference in high-energy phosphate metabolism was detected between groups. A different time dependence of tissue pH and specific gravity changes after 12 min of ischemia was detected. The present study suggests that the duration of an ischemic event marks the time of onset of brain tissue alkalosis and its duration and that cerebral edema alone cannot explain the pH changes.

Alkalosis↗

Event-related slow potentials and associated catecholamine function in migraine.

Plasma norepinephrine and dopamine and event-related slow potentials were measured at menses and ovulation in migraine with and without aura relative to normal subjects. The results indicated that at menses, but not ovulation, plasma dopamine was increased and norepinephrine was decreased relative to normal. This catecholamine imbalance was greater in migraine without aura than in migraine with aura. Conversely, event-related slow potentials measured over the posterior cortex at ovulation but not at the menses was altered relative to normal. Early epoch negativity was reduced in migraine with aura, whereas late epoch negativity was reduced in migraine without aura. The results suggested that (a) migraine without aura may involve dynamic shifts in the function of both norepinephrine and dopamine responsive neurons; (b) pathophysiology of migraine with aura is less dependent on catecholamine imbalance (norepinephrine alone affected); (c) these pathophysiological mechanisms are most prevalent in or restricted to posterior cortical regions but may be modulated by brainstem mechanisms.

Adult↗

Integrin-associated protein: a 50-kD plasma membrane antigen physically and functionally associated with integrins.

Phagocytosis by monocytes or neutrophils can be enhanced by interaction with several proteins or synthetic peptides containing the Arg-Gly-Asp sequence. Recently we showed that an mAb, B6H12, specifically inhibited this enhancement of neutrophil phagocytosis by inhibiting Arg-Gly-Asp binding to the leukocyte response integrin (Gresham, H. D., J. L. Goodwin, P. M. Allen, D. C. Anderson, and E. J. Brown. 1989. J. Cell Biol. 108:1935-1943). Now, we have purified the antigen recognized by B6H12 to homogeneity. Surprisingly, it is a 50-kD molecule that is expressed on the plasma membranes of all hematopoietic cells, including erythrocytes, which express no known integrins. On platelets and placenta, but not on erythrocytes, this protein is associated with an integrin that can be recognized by an anti-beta 3 antibody. In addition, both the anti-beta 3 and several mAbs recognizing the 50-kD protein inhibit Arg-Gly-Asp stimulation of phagocytosis. These data demonstrate an association between integrins and the 50-kD protein on several cell types. For this reason, we call it Integrin-associated Protein (IAP). We hypothesize that IAP may play a role in signal transduction for enhanced phagocytosis by Arg-Gly-Asp ligands.

Amino Acid Sequence↗

Risk factors for Clostridium difficile toxin-associated diarrhea.

The hospital-wide attack rate for Clostridium difficile-associated diarrhea at our tertiary-care university hospital was 0.02 per 100 patient discharges (0.02%) in 1982, but 0.41% and 1.47% in 1986 and 1987, respectively, with a peak incidence of 2.25% in the fourth quarter of 1987. Hospital antibiotic usage patterns showed concurrent increased use of third-generation cephalosporins, and intravenous vancomycin and metronidazole. Thirty-seven cases selected for study were older than 37 control patients, more likely to have an underlying malignancy and less likely hospitalized on the obstetrics/gynecology service. Their mean duration of hospitalization prior to diagnosis was 21 days, versus a mean total length of stay of eight days for controls. All cases received antibiotics, compared to 24 of the controls. Cases were given more antibiotics for longer periods, and more often received clindamycin, third-generation cephalosporins, aminoglycosides and vancomycin. Gender, race, duration of hospitalization, prior surgery and antiulcer therapy were not significant by logistic regression analysis. Epidemiologic variables with significantly different adjusted odds ratios (95% confidence intervals) were age greater than 65 years (14.1, 1.4-141), intensive care unit residence (39.2, 2.2-713), gastrointestinal procedure (23.2, 2.1-255) and more than ten antibiotic days (summation of days of each antibiotic administered) (16.1, 2.2-117). Control measures included encouraging earlier isolation and treatment of suspected cases and formulary restriction of clindamycin, with use of metronidazole for therapy of anaerobic infections. By the second half of 1988, the attack rate had dropped progressively to 0.74%.

Adult↗

Problems in the use of video recordings in training for psychotherapy.

In Britain, personnel of the state psychiatric service provide many forms of psychotherapy, to very many people. To train psychologists, psychiatrists and other professionals is therefore a large-scale task. To simplify and economize on this task, teaching methods are sought which attempt to provide the trainee with models of behaviour (towards the patient) which are efficacious. This paper offers a discussion of some theoretical and practical problems involved in this approach, which may affect both the therapeutic task and the development of the therapist.

Curriculum↗

Sensorineural hearing loss: a reversible effect of valproic acid.

We report 2 patients over the age of 70 who, while on valproate (VPA) for complex partial seizures, developed sensorineural hearing loss. Following discontinuation of VPA for nonaudiologic reasons, the patients reported improved hearing which was confirmed by audiometry. These findings represent VPA-induced sensorineural hearing loss, possibly in preexisting presbycusis.

Aged↗

Distinct binding sites for Ins(1,4,5)P3 and Ins(1,3,4,5)P4 in bovine parathyroid glands.

We utilized high specific activity, [32P]-labelled ligands to measure the binding of Ins(1,3,4,5)P4 and Ins(1,4,5)P3 to membranes prepared from bovine parathyroid glands. [32P]Ins(1,3,4,5)P4 bound rapidly and reversibly to parathyroid membranes, and the binding data could be fitted by the interaction of the ligand with two sites, one with Kd = 6.8 x 10(-9) M and Bmax = 26 fmol/mg protein and a second, lower affinity site, with Kd = 4.1 x 10(-7) M and Bmax = 400 fmol/mg protein. InsP5 was 10-20 fold less potent than InsP4, and Ins(1,3,4)P3 and Ins(1,4,5)P3 were nearly 1000-fold less potent in displacing [32P]Ins(1,3,4,5)P4. [32P]Ins(1,4,5)P3, on the other hand, bound to a single class of sites with Kd = 7.6 x 10(-9) M and Bmax = 34 fmol/mg. While the binding of [32P]Ins(1,4,5)P3 increased markedly on raising pH from 5 to 8, the binding of [32P]Ins(1,3,4,5)P4 decreased by 75% over this range of pH. Thus, [32P]-labelled Ins(1,3,4,5)P4 and Ins(1,4,5)P3 may be used to identify distinct binding sites which may represent physiologically relevant intracellular receptors for InsP3 and InsP4 in parathyroid cells.

Animals↗

Rhodococcus peritonitis in a patient treated with peritoneal dialysis.

This report is of a patient treated with continuous ambulatory peritoneal dialysis who developed peritonitis attributed to a Rhodococcus species. The rhodococci are rarely pathogenic to humans, and there are no previous reports of peritonitis associated with these organisms. It is important for clinicians to be aware of these bacteria because they can be acid-fast and can be confused with mycobacteria. They are often reported as "diphtheroids" but should not be considered contaminants.

Actinomycetales Infections↗

The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat: comparison to normothermia and hyperthermia.

The metabolic effects of graded whole body hypothermia on complete global cerebral ischemia and recirculation was investigated in the cat. Hypothermia was induced to one of three levels prior to ischemia; T = 26.8 degrees +/- 0.5 degrees C (n = 4), T = 32.1 degrees +/- 0.2 degrees C (n = 5), and T = 34.6 degrees +/- 0.3 degrees C (n = 6), and maintained constant throughout 16 min of ischemia and 1.5-2 h of recirculation. Intracellular cerebral pH and relative concentrations of high-energy phosphate metabolites were continuously monitored, using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Except for the first 4 min of ischemia, no significant differences were detected in the response of adenylate intensities and intracellular pH to ischemia and recirculation between the hypothermic groups. The three hypothermic groups were then pooled into one group, and the data compared to previously published data from a normothermic group, T = 38.4 degrees +/- 0.6 degrees C (n = 14), and a hyperthermic group, T = 40.6 degrees +/- 0.2 degrees C (n = 9), subjected to the identical ischemic and NMR measurement protocols. The hypothermic animals exhibited a statistically significant reduction of cerebral intracellular acidosis, both during ischemia and recirculation, as well as a more rapid return of adenylate intensities during recirculation, compared to the normothermic or hyperthermic groups. The data thus suggest that mild hypothermia has an ameliorative affect on brain energy metabolism and intracellular pH under conditions of complete global cerebral ischemia and recirculation.

Animals↗

Exploration of the microbial anatomy of normal human skin by using plasmid profiles of coagulase-negative staphylococci: search for the reservoir of resident skin flora.

The aerobic bacterial flora of the top 25 layers of the stratum corneum of normal human skin was characterized by sampling glabrous skin with contact plates and analyzing plasmid patterns of coagulase-negative staphylococci (SCN) by agarose gel electrophoresis. The number of colonies of SCN on the skin surface at 12 sites varied from 14 to 838. Removal of five keratinized layers by sequential stripping with cellophane tape reduced the number of colonies by 80% (median; range, 42%-91%). Counts remained constant during removal of 20 additional layers. SCN with six different plasmid patterns were identified at a site on the skin surface. After removal of 25 layers, colonies with a single pattern were clustered in one quadrant of the site. The site was sterilized and covered with a sterile dressing for 18 h. Colonies reappeared in the same quadrant of the site; six of seven had the same pattern seen 18 h previously. Observations at three other sites were similar. Reappearance of the same strain(s) of SCN following sterilization of the site suggests that the reservoir for normal resident skin flora is located below the stratum corneum, perhaps in hair follicles and ducts of sebaceous glands.

DNA, Bacterial↗

Platypnea-orthodeoxia and progressive autonomic failure.

Platypnea-orthodeoxia has been described in patients with pulmonary shunts, intracardiac shunts, and severe lung disease. We report a case of platypnea-orthodeoxia in a patient with minimal obstructive lung disease and progressive autonomic failure. We have shown our patient's symptoms to be the result of an orthostatic increase in ventilation-perfusion mismatching and to be corrected with fluid challenge.

Autonomic Nervous System Diseases↗

The effects of high extracellular Ca2+ and Mg2+ concentrations on the levels of inositol 1,3,4,5-tetrakisphosphate in bovine parathyroid cells.

We examined the effects of calcium (Ca2+), magnesium (Mg2+), and fluoride ion (F-) on inositol phosphate accumulation in bovine parathyroid cells prelabeled with [3H] inositol to determine whether these agents might modulate cytosolic Ca2+ through accumulation of intracellular inositol 1,3,4,5-tetrakisphosphate (IP4), which has been postulated to be a mediator of the influx of extracellular Ca2+. Both Ca2+ and Mg2+ produced dose-dependent increases in IP4 in the presence of Li+, with maximal 19- and 4-fold increases with 5.0 mM Ca2+ and 20 mM Mg2+, respectively. A 50% rise in IP4 was evident within 1 min in response to 5.0 mM Ca2+. In the absence of Li+, a 2-fold increase in IP4 was seen with 5.0 mM Ca2+ only after 15 min. Fluoride ion generated a dose-dependent increase in IP4, with a 48% rise at 10 mM F-, presumably by activating phospholipase-C through a guanine nucleotide regulatory (G) protein-dependent process. We conclude that inositol 1,4,5-trisphosphate generated in response to high extracellular Ca2+ and Mg2+ concentrations can be converted to IP4 in parathyroid cells. The slow kinetics for the increase in IP4 with high Ca2+ in the absence of Li+, however, do not support a role for IP4 in the early phase of the sustained increase in cytosolic Ca2+ produced by high extracellular Ca2+ concentrations.

Animals↗

Transient hyperthermia protects against subsequent forebrain ischemic cell damage in the rat.

We heated Wistar rats (n = 10) to 41.5 +/- 0.2 degrees C for 15 minutes, 24 hours before the induction of forebrain cerebral ischemia. We subjected 23 rats to forebrain ischemia without prior heating. Ischemic cell damage in the medial, lateral, and overall CA 1/2 hippocampus, inferior frontal cortex, and dorsal-lateral striatum was significantly (p less than 0.05) less severe in heated animals than in nonheated animals.

Animals↗

Miliary PCP in AIDS.

The most frequent radiographic presentation of (PCP) is bilateral interstitial or alveolar infiltrates. Atypical features include lobar distribution, pleural effusions, hilar adenopathy, cyst formation and spontaneous pneumothorax. A diffuse miliary pattern has not been described previously for PCP. A 30-year-old male intravenous drug abuser, with AIDS, presented to our institution complaining of fever and productive cough. Admission chest x-ray film revealed a "classic" miliary pattern. Sputum smears were negative for acid-fast bacilli and both bronchoalveolar lavage and transbronchial biopsy revealed only PCP. Repeat bronchoscopy one month later was unrevealing and marked x-ray resolution occurred after treatment with pentamidine alone. The incidence of atypical roentgenographic features of PCP in AIDS is approximately 10 percent. Given the frequency of this infection in AIDS, knowledge of the unusual presentations is imperative. Based on this report, PCP must be included in the differential diagnosis of a miliary x-ray pattern.

Acquired Immunodeficiency Syndrome↗

Brain ischemia.

The sensitivity of MRI to changes in water state and volume makes it the most desirable modality for imaging early brain ischemia. Its sensitivity is reflected in the ability to show ischemic changes in the white matter of the asymptomatic elderly, which are attributed to axonal loss, demyelination, and gliosis. In large infarcts, however, contrast enhancement with Gd-DTPA can be used to add specificity, should doubt exist as to the proper diagnosis. The ability of MR to image flow is a valuable adjunct, and MR angiography has the potential partially to replace invasive angiography. Applications of MR such as diffusion-perfusion studies, sodium imaging, and spectroscopy could all prove to be useful in the future.

Aged↗