An advanced physical diagnosis course for internal medicine residents.
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Biomedical subjects
Publications and source records attributed to J M Wood.
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Human keratinocytes under in vitro conditions synthesize norepinephrine and epinephrine, whereas melanocytes lack this capacity. Keratinocytes established from lesional and nonlesional skin of patients with vitiligo synthesized four and two times more norepinephrine, respectively, than controls. Epinephrine synthesis was similar in keratinocytes from uninvolved epidermis and controls, but cells from involved skin had 6.5-fold less epinephrine than controls, indicative of low phenylehtanolamine-N-methyl transferase (PNMT) activity. Similar results were obtained in five patients with vitiligo who showed low epinephrine levels in involved epidermis. Both human keratinocytes and melanocytes expressed significant levels of monoamine oxidase A (MAO-A) activities as shown using 14C-labelled 5-hydroxytryptamine as substrate and immunohistochemical staining with mouse monoclonal antibody. MAO-A activities in the total epidermis of patients with vitiligo were increased five- to ten-fold compared with skin of type-matched controls. Similar increases in MAO-A activities were also found in both keratinocytes and melanocytes established in vitro from vitiliginous epidermis. Based on these results, it can be concluded that defective catecholamine synthesis in the epidermis of patients with vitiligo leads to increased levels of norepinephrine with a concomitant increase in MAO-A activity.
This review explores whether the therapeutic attractiveness of renin inhibitors compared with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, is sufficient to warrant continued interest in their development for the treatment of cardiovascular disease. Clinical and experimental data available to date indicate that patients with hypertension and congestive heart failure will benefit from renin inhibition. However, clinical experience is very limited, and extra benefits of renin inhibitors compared with the other blockers of the renin-angiotensin system (RAS) have yet to be demonstrated. Some experimental data in animals and humans point to a greater effect of acute renin inhibition on renal blood flow than other modes of interference with the RAS. Again, the clinical benefits of such an effect, and particularly after long-term treatment, in hypertension and renal disease need to be determined. In today's cost-conscious health setting, only new drugs that bring additional clinical benefits have a good chance of being commercially viable. It remains to be seen whether renin inhibitors will fulfill these criteria.
Children's disclosure of sexual abuse has been described as a quasi-developmental process that includes stages of denial, reluctance, disclosure, recantation, and reaffirmation (Sorenson & Snow, 1991, Summit, 1983). It has been reported that nearly 75% of sexual abuse victims initially deny abuse, and that nearly 25% eventually recant their allegations (Sorenson & Snow, 1991). The present study examined disclosures in 234 sexual abuse cases validated by Protective Services in El Paso, Texas. Denial of abuse occurred in 6% of cases, and recantation in 4% of cases in which a child had already disclosed abuse. Four of the eight victims who recanted appeared to do so in response to pressure from a caretaker. The Child Sexual Abuse Accommodation Syndrome described by Summit (1983) seems to be infrequent among the types of cases seen by child protection agencies. The present findings do not support the view that disclosure is a quasi-developmental process that follows sequential stages.
Membrane properties that vary as a result of isotropic and transmembrane osmolality variations (osmotic stress) are of considerable relevance to mechanisms such as osmoregulation, in which a biological system "senses" and responds to changes in the osmotic environment. In this paper the light-scattering behavior of a model system consisting of large unilamellar vesicles of dioleoyl phosphatidyl glycerol (DOPG) is examined as a function of their osmotic environment. Osmotic downshifts lead to marked reductions in the scattered intensity, whereas osmotic upshifts lead to strong intensity increases. It is shown that these changes in the scattering intensity involve changes in the refractive index of the membrane bilayer that result from an alteration in the extent of hydration and/or the phospholipid packing density. By considering the energetics of osmotically stressed vesicles, and from explicit analysis of the Rayleigh-Gans-Debye scattering factors for spherical and ellipsoidal shells, we quantitatively demonstrate that although changes in vesicle volume and shape can arise in response to the imposition of osmotic stress, these factors alone cannot account for the observed changes in scattered intensity.
We used noninvasive Fourier transform (FT) Raman spectroscopy to follow the fate of the broadly used ultraviolet UVA sun blocker, oxybenzone, after topical application to the skin. Our results showed that oxybenzone is rapidly photo-oxidized, yielding oxybenzone semiquinone, a potent electrophile, which reacts with thiol groups on important anti-oxidant enzymes and substrates, such as thioredoxin reductase and reduced glutathione, respectively. Although oxybenzone is an excellent broad spectrum UVA filter, its rapid oxidation followed by the inactivation of important antioxidant systems indicates that this substance may be rather harmful to the homeostasis of the epidermis. Furthermore, these results demonstrate that FT-Raman spectroscopy is a useful method for studying the transport and metabolism of active ingredients in topical preparations.
The osmolality of rhizosphere soil water is expected to be elevated in relation to bulk-soil water osmolality as a result of the exclusion of solutes by plant roots during water uptake, the release of plant root exudates, and the production of exopolymers by plant roots and rhizobacteria. In contrast, the osmolality of water within highly hydrated bulk soil is low (less than 50 Osm/kg); thus the ability to adapt to elevated osmolality is likely to be important for successful rhizosphere colonization by rhizobacteria. The present review focuses on the osmoadaptive responses of three gram-negative rhizobacterial genera: Rhizobium, Azospirillum, and Pseudomonas. Specifically, we examine the compatible solutes and osmoprotectants utilized by various species within these genera. The adaptation of rhizobacteria to hypoosmotic environments is also examined in the present review. In particular, we focus on the biosynthesis and accumulation of periplasmic glucans by rhizobacteria. Finally, the relationship between rhizobacterial osmoadaptation and selected plant-microbe interactions is considered.
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Changes in microcirculation play an important role in the pathogenesis and maintenance of hypertension. The changes can be due to an alteration in vessel diameter or in the number of small blood vessels. In this study, the effects of prolonged administration of different blockers of the renin angiotensin system on the microcirculation of the cutaneous maximus muscle of young spontaneously hypertensive rats were determined by using the dorsal microcirculatory chamber model. Animals were treated with the angiotensin-converting enzyme inhibitor (ACE inhibitor) benazeprilat (3 mg/kg/d) or the specific angiotensin II AT1 receptor antagonist valsartan (3 mg/kg/d) for 4 weeks. Blood pressure was significantly lowered by 22 to 33% and to a similar extent in both treatment groups, whereas blood pressure in the control group continued to rise. Microvascular diameters and density were measured before and during the drug treatment and compared with those in the control group. There was no significant effect of either of the drug treatments on vascular diameters when compared with the control group for any vessel type (arterioles or venules). In contrast, there was a significant decrease in small arteriolar and venular density and in large venular density after treatment with the ACE inhibitor, whereas the angiotensin II AT1 receptor antagonist had no significant effect. The data do not suggest a role for angiotensin II in the long-term control of striated muscle microvascular tone. However, angiotensin II may be involved in microvascular growth via a non-AT1 receptor-mediated mechanism, or other vasoactive peptides degraded by ACE may contribute to the effects of the ACE inhibitor.
A commonly used clinical technique for determining whether visual function is abnormal, particularly when a patient is suspected of having unilateral or asymmetric disease, is to compare the visual function of the 'suspect' eye to that of the normal eye. This assumes that in normal patients visual function in each eye is equal and that this symmetry is maintained with age. To determine the extent of normal symmetry for clinical measures of visual function, we assessed high and low contrast visual acuity, letter contrast sensitivity and motion sensitivity (Dmin) in both eyes of a group of 91 subjects spanning an age range of 21 to 82 years. For the whole group the interocular differences in sensitivity for each of the tests approximated a Gaussian distribution. The results demonstrate that interocular differences should exceed more than 0.16 and 0.17 logMAR (approximately 2 lines) for high and low contrast visual acuity respectively, before patients can be considered to be outside the range of normality. For the Pelli-Robson Chart, interocular differences must exceed 0.23 log CS (1.5 triplets, 4.5 letters) and for Dmin, more than 0.35 log minarc for the differences to be considered abnormal. For low contrast letter visual acuity, there was a trend for the absolute interocular differences to increase significantly with age, but asymmetry remained relatively constant for the other visual measures.
(6R)5,6,7,8-tetrahydrobiopterin (6-BH4) directly regulates tyrosinase activity by specifically binding to a putative 13 amino acid domain. This domain has sequence homology to 6-BH4 binding sites already identified on phenylalanine hydroxylase and 4a-carbinolamine dehydratase. Furthermore, this binding sequence appears to have been conserved during the evolution of tyrosinase as it has also been identified in the frog, mouse and human enzymes. 6-BH4 controls tyrosinase activity by an uncompetitive mechanism requiring the presence of L-tyrosine for effective down-regulation. When L-dopa is substrate, 6-BH4 does not inhibit the enzyme implicating separate binding sites for L-dopa and L-tyrosine on tyrosinase. Dihydropterin and 6-biopterin, the oxidation products of 6-BH4, do not inhibit tyrosinase significantly, indicating that melanin biosynthesis is controlled by a 6-BH4/6-biopterin redox-switch mechanism which can be initiated by photo-oxidation of 6-BH4.
One hundred sixty-one professionals and 97 undergraduates were asked to (a) prioritize 12 hypothetical CPS cases on the basis of sexual behaviors displayed by children, and (b) estimate the probability of abuse in a single case involving a child who had displayed sexual behavior and came from a population with a known base rate of abuse. When asked to prioritize the 12 cases as "high," "medium," or "low" on the basis of sexual behaviors, professionals were more accurate than students. However, when asked to estimate the probability of abuse in the single case, both professionals and students failed to incorporate base rate information into their decisions. As a result, both groups misestimated the probability of abuse under some circumstances. Professionals' performance on both judgment tasks was unrelated to level of experience with sexual abuse cases.
Pre- and post-vaccination sera from 19 volunteers were analysed by the haemagglutination inhibition (HI) test, virus neutralization (VN) assay and avidity enzyme-linked immunosorbent assay (ELISA). The sera were tested against the three strains in a commercial inactivated influenza vaccine; A/Beijing/353/89(H3N2); A/Taiwan/1/86 (H1N1) and B/Yamagata/16/88. Additionally, a range of earlier strains and one newer isolate were assayed for HI- and VN-antibodies. Large variations in the pre-vaccination HI titres were observed for the viruses tested. However, 8-9 days after vaccination HI titres increased to above the assumed protective level (HI > or = 40) in most subjects. Although a limited number of patients were analysed at each sampling point, the time-profile we observed in this study is consistent with data we have obtained in earlier trials (Cox, R.J. et al., Vaccine 1994, 12,993-999). The VN titres, on the other hand, were low against all influenza strains before and up to 6 days, but increased rapidly 8-9 days after vaccination. A recent H3N2 isolate, A/Beijing/32/92 (H3N2), which had drifted further away from the vaccine strain, reacted to low titres or were negative in both the HI and VN assays. No change in the serum avidity to the influenza surface antigens was detected after vaccination, whereas sera from subjects naturally infected with influenza showed an increase in avidity to the infecting virus strain. The increase in serum avidity observed in the infected subjects is probably due to the increased and prolonged antigenic stimulus provided by the replicating virus.
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BACKGROUND: The effect of simulated visual impairment on the driving performance of elderly subjects and the relation between changes in driving performance and vision were investigated. METHODS: Vision was impaired by goggles simulating the effects of cataracts, binocular visual field restriction, and monocularity. Driving was assessed on a road circuit free of other vehicles. Visual performance was measured using the Humphrey Field Analyser (HFA), the Useful Field of View (UFOV), and the Pelli-Robson chart. RESULTS: The simulated visual impairment significantly decreased driving performance, even though all drivers satisfied the legal visual requirements for driving. Significant correlations between driving performance and the UFOV and Pelli-Robson chart were found.
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Human keratinocytes have the capacity to synthesize catecholamines from L-tyrosine, which in turn is produced from L-phenylalanine via phenylalanine hydroxylase. This enzyme activity is controlled by the supply of the essential cofactor/electron donor (6R)5,6,7,8 tetrahydrobiopterin (6-BH4). Undifferentiated keratinocytes express high levels of the rate-limiting enzymes for the de novo synthesis of 6-BH4, i.e., GTP-cyclohydrolase-1, and for its recycling, i.e., 4a-hydroxytetrahydrobiopterin dehydratase. As a consequence of 6-BH4 synthesis, phenylalanine hydroxylase is activated, yielding L-tyrosine, which in the presence of excess 6-BH4 turns on the biosynthesis of catecholamines via the rate-limiting enzyme tyrosine hydroxylase. Therefore, undifferentiated keratinocytes contain high levels of the catecholamine system yielding sufficient levels of norepinephrine and epinephrine, required for the induction of beta-2-adrenoceptors. Stimulation of beta-2-adrenoceptors by epinephrine causes a rise in intracellular calcium via extracellular influx. This event corresponds with keratinocyte differentiation. In differentiated keratinocytes, all enzyme activities involved in 6-BH4, L-tyrosine, and epinephrine biosynthesis are decreased, resulting in significantly lower levels of epinephrine and a concomitant decrease in the expression of beta-2-adrenoceptors. These data strongly suggest a connection between catecholamine biosynthesis, beta-2-adrenoceptor expression, calcium flux, and the differentiation of keratinocytes in human epidermis.