Unusual Sensitivity Research Articles

Unusual combined sensitization to palladium and other metals

Contact DermatitisVolume 24, Issue 2 p. 131-132 Unusual combined sensitization to palladium and other metals H. Hackel, H. Hackel Department of Dermatovenereology, Julius-Maximilians-University, Josef-Schneiderstr 2, 8700 Würzburg, FRGSearch for more papers by this authorK. Miller, K. Miller Department of Dermatovenereology, Julius-Maximilians-University, Josef-Schneiderstr 2, 8700 Würzburg, FRGSearch for more papers by this authorP. Elsner, P. Elsner Department of Dermatovenereology, Julius-Maximilians-University, Josef-Schneiderstr 2, 8700 Würzburg, FRGSearch for more papers by this authorG. Burg, G. Burg Department of Dermatovenereology, Julius-Maximilians-University, Josef-Schneiderstr 2, 8700 Würzburg, FRGSearch for more papers by this author H. Hackel, H. Hackel Department of Dermatovenereology, Julius-Maximilians-University, Josef-Schneiderstr 2, 8700 Würzburg, FRGSearch for more papers by this authorK. Miller, K. Miller Department of Dermatovenereology, Julius-Maximilians-University, Josef-Schneiderstr 2, 8700 Würzburg, FRGSearch for more papers by this authorP. Elsner, P. Elsner Department of Dermatovenereology, Julius-Maximilians-University, Josef-Schneiderstr 2, 8700 Würzburg, FRGSearch for more papers by this authorG. Burg, G. Burg Department of Dermatovenereology, Julius-Maximilians-University, Josef-Schneiderstr 2, 8700 Würzburg, FRGSearch for more papers by this author First published: February 1991 https://doi.org/10.1111/j.1600-0536.1991.tb01665.xCitations: 26AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume24, Issue2February 1991Pages 131-132 RelatedInformation

Preparation and characterization of aliphatic diphenyl esters intended as precursors for polyesters

Abstract An extensive number of aliphatic diphenyl esters, C6H5OOC(CH2)nCOOC6H5 (n=0,...,8,10,11,12,14), have been prepared in pure form. The crystalline melting points of these esters exhibit an odd-even temperature behaviour, with the higher-melting even series (n even) displaying a minimum for n = 8 while the odd series shows an almost monotonic slow increase. High-resolution 13C nuclear magnetic resonance (n.m.r.) spectroscopy of the esters in CDCl3 and C6D6 allows all non-symmetrical carbons to be resolved, even the seven different methylenes for n = 14. This unusual spectral sensitivity is primarily based on similar data from phenyl esters, interpreted as the results of an apparent macrocyclic conformation of the larger diphenyl esters. High-performance size exclusion chromatography (s.e.c.) of diphenyl esters, phenyl esters, aromatic and linear hydrocarbons in tetrahydrofuran, toluene and chloroform points to specific phenyl ester-solvent interactions, which obscure a potential s.e.c. conformational analysis of the diphenyl esters.

Steroids and hypertension

Primary aldosteronism is the principal disorder of zona glomerulosa and a number of subsets have been identified: unilateral adenoma; bilateral micro- or macro-nodular hyperplasia (idiopathic aldosteronism); primary hyperplasia and aldosterone-producing carcinoma either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets are now quite reliable and our experience is presented in detail. Unfortunately the pathogenesis of most of these forms is still poorly recognized and requires further investigation. An extreme sensitivity to angiotensin II is present in patients with idiopathic aldosteronism, and a role for adrenal renin is now being advocated. A peculiar form of hyperaldosteronism is the glucocorticoid-remediable subtype. An unusual sensitivity of aldosterone to ACTH is present in this form. A qualitative biochemical abnormality in this disorder consists of marked over-production of products of the cortisol C18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with three affected sibs has been studied by our group. In other clinical situations, classical zona fasciculata mineralocorticoids [deoxycorticosterone (DOC), corticosterone and their 18-hydroxy compounds] are secreted in excess. The hypertensive diseases of this zone are rare DOC-secreting tumors and two forms of congenital adrenal hyperplasia (CAH), the 11β-hydroxylase (11-OHDS) and the 17α-hydroxylase deficiency syndromes (17-OHDS), which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-OHDS, while all ACTH-dependent MCH are very high in the 17-OHDS. The molecular basis of gene abnormalities of this disorder are currently under investigation, and preliminary data obtained in some of our patients are presented. Finally a syndrome of apparent mineralocorticoid excess, which is not a primary disorder of the adrenal cortex, describes the association of an unexplained hypermineralocorticoid state with a decreased rate of peripheral 11β-hydroxy dehydrogenation of cortisol to cortisone. Studies on this syndrome have led to the hypothesis that peripheral cortisol inactivation is the normal mechanism permitting specific mineralocorticoid recognition. The syndrome exists in two forms both characterized by a decreased turnover of a normal level of plasma cortisol, but in the type I variant an elevated cortisol/cortisone metabolite ratio is found, whereas in the type II variant this ratio is normal. Three patients of the latter form have recently been described by us and are shortly illustrated. A possible role of this impaired metabolism of cortisol in the pathogenesis of other forms of hypertension such as liquorice and carbenoxolone-induced hypertension has recently been suggested.

Defective Fasciculata Zone Function as the Mechanism of Glucocorticoid-Remediable Aldosteronism*

Glucocorticoid-remediable aldosteronism is characterized by unusual sensitivity of aldosterone secretion to ACTH. Suppressibility by glucocorticoid and continued stimulability by exogenous ACTH has provided the basis for diagnosis and treatment of the disorder. A qualitative biochemical abnormality consisting of marked overproduction of the products of the cortisol C-18 oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, has been examined in 10 patients with the disorder and compared to the normal C-18 oxidation products of corticosterone, aldosterone, and 18-hydroxycorticosterone. The technique, based on stable isotope dilution mass fragmentography, measured the tetrahydro urinary metabolites of aldosterone, 18-hydroxycorticosterone, and 18-oxocortisol and unmetabolized 18-hydroxycortisol. All 4 C-18 oxygenated corticosteroids were markedly elevated in the untreated state and showed rapid parallel suppression with low doses of glucocorticoid. The proportional changes in C-18 oxygenated cortisols together with aldosterone and 18-hydroxycorticosterone suggested the mechanism of a common catalytic site of a cytochrome P450 methyl oxidase serving both cortisol and corticosterone substrates. The ACTH-dependent secretion of the C-18 oxidation products of both corticosterone and cortisol in the disorder is attributed to the acquisition of methyl oxidase activity by the fasciculata zone, where there are abundant pools of these precursors.

Interdisciplinary Approach to Assessing the Health Risk of Air Toxic Chemicals: An Overview

To assist the regulatory branch of the Environmental Protection Agency in addressing the risk assessment of air toxics, the Health Effects Research Laboratory initiated a comprehensive inhalation toxicology program to provide key health effects data missing from the current data base. A priority ranking of chemicals based on the potential for substantial human exposure and the need for health effects data was developed to identify candidate chemicals for toxicological research. The major goal of the program is to evaluate the concentration-response from acute, intermittent and subchronic inhalation exposures to developmental, genetic, hepatic, immunologic, neurologic, pulmonary and reproductive toxicity in a manner that provides data for the regulatory health assessment of air toxic chemicals. Extrapolation and dosimetry research is also conducted to improve the basis for human risk assessment. Determination of biological endpoints to be examined will be decided on a compound-by-compound basis, depending on the physical, chemical and structural characteristics of the chemical and evaluation of the existing health data base. Although the main emphasis is on inhalation as the primary route of exposure, some of the laboratories will compare inhalation to other routes, such as oral, to better understand the influence of route of exposure and hence the potential applicability of existing health data. Acute and intermittent exposures will be done for all compounds. Upon evaluation of the acute results, a decision will be made as to whether subchronic studies are needed. Endpoints that show unusual sensitivity may be investigated in greater detail. The total length of exposure will vary from 1 to 21 days. The daily length of exposure will range from 1 to 8 hr. If adverse effects are observed at ambient levels, the time to recovery after exposure will be investigated.

Phenotypic and molecular biological analysis of human butyrylcholinesterase variants

Our laboratory has recently shown that several variant forms of human butyrylcholinesterase, associated with unusual sensitivity to succinylcholine, are caused by specific mutations within the structural DNA coding for this enzyme. Atypical (dibucaine-resistant) butyrylcholinesterase is caused by a point mutation at nucleotide position 209(GAT-- greater than GGT), which changes aspartate 70 to glycine. One fluoride-resistant variant family has a point mutation at nucleotide 728(ACG-- greater than ATG), which changes threonine 243 to methionine. Another type of fluoride-resistant variant has a point mutation at nucleotide 1169(GGT-- greater than GTT), which changes glycine 390 to valine. One type of silent phenotype is due to a frame-shift mutation at nucleotide position 351(GGT-- greater than GGAG). A polymorphic site at nucleotide position 1615 (GCA/ACA), coding for Ala/Thr, accounts for the quantitative K-variant, which causes an approximate one-third reduction of activity, if Thr occupies that position at codon 539. Examples are given to illustrate the advantages of using a combination of the new DNA analytical techniques, including: the use of allele-specific probes, with the standard serum cholinesterase phenotyping methods. More accurate typing of patients with certain variants is now possible; pedigree analysis will be aided by the improved methodology.

Respiratory and cardiovascular effects of tetrodotoxin in urethane-anesthetized guinea pigs

Cardiorespiratory effects of tetrodotoxin (TTX) (15 μg/kg, i.p.) were investigated in urethane-anesthetized guinea pigs acutely instrumented for the recording of medullary respiratory-related units (RRUs), diaphragm electromyogram (DEMG), electrocorticogram (ECoG), electrocardiogram (ECG), blood pressure (BP), endtidal CO 2, and arterial O 2 and CO 2. Respiratory system responses showed a hyperventilatory profile during the initial stage of intoxication. This was followed by an abrupt onset of a progressive decrease in the respiratory frequency, and a respiratory rate depression-related respiratory failure. The average time to TTX-induced respiratory arrest and death was 10.3 ± 4.2 min. Concurrentlyecorded inspiratory and expiratory RRU activities indicated that respiration invariably failed in an end-expiratory. position as manifested by a sustained period of expiratory RRU discharge. The progressive rate depression prior to respiratory arrest was temporally correlated only to a concomitantly augmenting expiratory RRU discharge duration. Inspiratory RRU discharge duration, on the other hand, did not display any significant change throughout the course of intoxication. The asymmetry in RRU response patterns indicates either an expiratory network component's particular sensitivity to perturbation by TTX or a dissociative trend in some bulbar respiratory rhythmogenic mechanisms. Peripheral cardiorespiratory changes were also quite profound. These included a gradual and steadfast decline in BP, a steadily decreasing amplitude in DEMG oscillations, and a state of progressive hypercapnia and hypoxenia. Changes in heart rate and ECG waveform attributes prior to respiratory arrest were not appreciable. In conclusion, in addition to a variety of TTX-induced peripheral cardiorespiratory effects, findings from this study have revealed a central respiratory system component that appears to show an unusual sensitivity to perturbation by TTX. The significance of this unique phenomenon as it relates to the nature and extent of TTX-induced central respiratory depression is discussed.

Intellectual Eclipse

Abstract In “The Intellectuals and the Powers” Shils defines intellectuals as members of society “with an unusual sensitivity to the sacred.” These minorities reflect on natural laws and social rules. Further, they are “desirous of being in frequent communion with symbols which are more general than the immediate concrete situations of everyday life.” Thus, “It is practically given by the nature of the intellectual's orientation that there should be some tension between the intellectuals and the value orientations embodied in the actual institutions of every society.” Shils is trying to distinguish intellectual activity from other forms of thinking. But is it justifiable to distinguish, e.g., as Znaniecki does in agreement with Shils, between the “technologist” and the “sage?”

Sexually Dimorphic Areas in the Brain of Whiptail Lizards

The whiptail lizard species Cnemidophorus inornatus exhibits sexually dimorphic mating behaviors. We report that complementary sexual dimorphisms exist in two hypothalamic regions in male and female C. inornatus. The anterior hypothalamus-preoptic area (AH-POA), which is involved in male-typical mounting and intromission behaviors, is larger in males. The ventromedial hypothalamus (VMH), which controls female-typical receptivity, is larger in females. The all-female whiptail lizard Cnemidophorus uniparens, a direct descendant of C. inornatus, regularly and reliably displays both male-like mounting and female-like receptive (pseudosexual) behaviors. Rather than having a male-like AH-POA, however, the AH-POA as well as the VMH of C. uniparens resemble that of female C. inornatus. The biological basis of pseudosexual behavior in the parthenogen appears to be due to an unusual sensitivity to ovarian progesterone rather than to a difference in brain morphology.

New Aspects of Mineralocorticoid Hypertension

Primary aldosteronism is the principal disorder of the zona glomerulosa, and a number of subsets have been identified: unilateral adenoma, bilateral micro- or macronodular hyperplasia (idiopathic aldosteronism), primary hyperplasia, and aldosterone-producing carcinoma, either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets are now quite reliable, and our experience is presented in detail. Unfortunately, the pathogenesis of most of these forms is still poorly recognized and requires further investigation. An extreme sensitivity to angiotensin II is present in patients with idiopathic aldosteronism, and a role of adrenal renin is now being advocated. A peculiar form of hyperaldosteronism is the glucocorticoid-remediable subtype. An unusual sensitivity of aldosterone to ACTH is present in this form. The qualitative biochemical abnormality in this disorder consists of a marked overproduction of products of the cortisol C-18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with 3 affected sibs has been studied by our group. In other clinical situations, classical zona fasciculata mineralocorticoids (deoxycorticosterone [DOC], corticosterone, and their 18-hydroxy compounds) are secreted in excess. The hypertensive diseases of this zone are rare DOC-secreting tumors and two forms of congenital adrenal hyperplasia, the 11 beta-hydroxylase and 17 alpha-hydroxylase deficiency syndromes, which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-hydroxylase deficiency syndromes, while all ACTH-dependent MCH levels are very high in the 17-hydroxylase deficiency syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Design and minimum reflux for heterogeneous azeotropic distillation columns

AbstractA simple design technique for heterogeneous distillation columns has been developed. The underlying geometric conditions which govern minimum reflux are shown to share certain common features with homogeneous distillations, but differ in some important respects. It is shown that heterogeneous columns display some unusual sensitivities to the design parameters. The most notable being the drastic swings in the composition and temperature profiles with very small changes in the level of trace impurities in the product stream.

Isolation of a formamidopyrimidine-DNA glycosylase (fpg) mutant of Escherichia coli K12.

The fpg+ gene of Escherichia coli coding for formamidopyrimidine-DNA glycosylase was previously cloned on a multicopy plasmid. The plasmid copy of the fpg+ gene was inactivated by cloning a kanamycin resistance gene into the open reading frame, yielding the fpg-1::Knr mutation. This mutation was transferred to the chromosome in the following steps: (i) linearization of the plasmid bearing the fpg-1::Knr mutation and transformation of competent bacteria (recB recC sbcB); (ii) selection for chromosomal integration of the fpg-1::Knr mutation; (iii) phage P1 mediated transduction of the fpg-1::Knr mutation in the AB1157 background. The resulting fpg- mutant exhibited no detectable Fapy-DNA glycosylase activity in crude lysates. The insertion mutation was localized by means of genetic crosses between mtl and pyrE, at 81.7 min on the E. coli linkage map. Sequence analysis confirmed this mapping and further showed that fpg is adjacent to rpmBG in the order fpg, rpmGB, pyrE. The formamidopyrimidine-DNA glycosylase defective strain does not show unusual sensitivity to the following DNA damaging treatments: (i) methylmethanesulfonate, (ii) N-methyl-N'-nitro-N-nitroso-guanidine, (iii) ultraviolet light, (iv) gamma-radiation. The fpg gene is neither part of the SOS regulon nor the adaptive response to alkylating agents.

Visual Spectral Sensitivities of Bioluminescent Deep-sea Crustaceans

The spectral sensitivities of eight species of deep-sea decapod shrimps (Family Oplophoridae) were determined from shipboard measurements of electroretinograms of dark-captured specimens. Notostomus gibbosus and N. elegans are maximally sensitive at 490 nm, and chromatic adaptation experiments indicate that a single visual pigment is present. Peak sensitivities of Acanthephyra smithi and A. curtirostris are at 510 nm, a longer wavelength than expected for such deep-sea dwellers. The four photophore-bearing species, Systellaspis debilis, Janicella spinacauda, Oplophorus spinosus, and O. gracilirostris have sensitivity maxima at 400 and 500 nm, and chromatic adaptation experiments indicate the presence of two visual pigments. This unusual short wavelength sensitivity may provide the basis for congener recognition based on the spectral bandwidth of luminescence.

High‐Dose Naloxone in Older Normal Subjects: Implications for Alzheimer's Disease

The behavioral and cognitive effects of naloxone HCl, in doses of 5 micrograms/kg, 0.1 mg/kg, and 2.0 mg/kg administered as an IV bolus, were assessed in a double-blind, placebo-controlled, randomized study of eight normal subjects ranging in age from 44 to 74 years (mean 63). Naloxone produced mild behavioral effects with slight cognitive impairment after the 2.0 mg/kg dose only. The threshold, dose dependency, characteristics, and magnitude of these behavioral effects were similar to what has previously been reported in young normal subjects, but markedly different from those observed in patients with dementia of the Alzheimer type (DAT) matched in age to the current study sample. These data suggest that the metabolic fate of naloxone is not substantially affected by age within the range studied. The findings of this study provide further support for a role for endogenous opiate systems in the modulation of behavior and cognition, and suggest that the unusual behavioral sensitivity of patients with DAT to naloxone cannot be accounted for by the effect of age.

Volatile general anaesthetics activate a novel neuronal K+ current

Although it is still controversial whether the primary target sites underlying general anaesthesia are proteins or lipids, it is generally thought that the ultimate targets are ion channels in nerve membranes. One approach to finding these targets is to study the effects of general anaesthetics on identified neurons, where differential effects on neuronal activity can be pursued to the molecular level. Here we report that amongst a group of apparently identical molluscan neurons having endogenous firing activity, a single cell displays an unusual sensitivity to volatile agents (which, at surgical levels, completely inhibit its activity). We further show that this sensitivity is due to a novel anaesthetic-activated K+ current, which is found in the sensitive cell but not in the surrounding insensitive cells. This K+ conductance is not appreciably voltage-gated and persists for as long as the anaesthetic is present. The response to anaesthetics is completely reversible and saturates at low anaesthetic partial pressures: the half-maximal response for halothane occurs at 0.0063 atm, close to its minimum alveolar concentration (0.0075 atm) in man.

Conditioned taste aversion produced by 2-deoxy-D-glucose in rats and hamsters

The glucose antimetabolite 2-deoxy-D-glucose (2DG) reliably causes hyperphagia in rats, but has consistently proven ineffective in producing overeating in golden hamsters. It was hypothesized that hamsters do not overeat following 2DG administration because of unusually strong aversive effects of the drug in this species. To test this hypothesis, rats and hamsters were tested in a conditioned taste aversion (CTA) paradigm, in which a novel 0.1% saccharin solution was paired on three occasions with intraperitoneal injections of either saline, lithium chloride (LiCl; 50 mg/kg), or 2DG (either 350 or 750 mg/kg). CTA was measured in 16 twenty-minute, two-bottle preference tests which were conducted at 2–3 day intervals following conditioning. LiCl and 2DG both produced strong and long-lasting aversions to saccharin solution in rats. However, 2DG was significantly less effective than LiCl in producing CTA in hamsters. It is unlikely, therefore, that the failure of 2DG to produce hyperphagia in hamsters is due primarily to an unusual sensitivity to the aversive effects of the drug.

Mouse kidney androgen-regulated protein messenger ribonucleic acid is expressed in the proximal convoluted tubules.

Kidney androgen-regulated protein (KAP) mRNA represents the most abundant [approximately 4% of the total poly(A) RNA] mRNA species that is induced by androgens in the mouse kidney. Comparison of the expression of several androgen-regulated mRNAs in this tissue, revealed that the mRNAs were differentially regulated by the hormone. KAP mRNA exhibited unusual sensitivity to low concentrations of the androgen-receptor complex. Because of its unusual characteristics, it was of interest to determine in what cells of the kidney KAP mRNA was being produced. Using the technique of in situ hybridization with single stranded RNA probes, we have identified the epithelial cells of the renal proximal convoluted tubules as the site of synthesis of KAP mRNA. Interestingly, only a subpopulation of these cells, those located in the juxtamedullary region of the renal cortex, contain KAP mRNA in castrated males. After androgen treatment, cortical proximal tubules are also induced to express KAP mRNA. These results suggest that two types of response to androgens occur in these cells. One is the progressive increase of KAP gene expression in the juxtamedullary region while the other involves recruitment of new cells in the cortical proximal tubules to synthesize KAP mRNA.

Vanadate-activated calcium influx in A431 cells is dependent on the plasma membrane potential.

Vanadate can activate the uptake of Ca in A431 epidermal carcinoma cells by two- to fivefold with no detectable lag period. Preincubation with epidermal growth factor (EGF) to down-regulate the EGF receptor prevents subsequent stimulation by EGF but not that by vanadate. Ca uptake is sodium-independent and is not activated by depolarization in high KCl. On the contrary, vanadate-stimulated uptake is completely inhibited by decreasing the plasma membrane potential from about -65 to -30 mV. These results demonstrate that the EGF receptor is not itself functioning as a Ca channel, that vanadate is not acting at the level of EGF receptor, and that the Ca transport system exhibits an unusual potential sensitivity in that it is inhibited by depolarization of the plasma membrane.

Ontogeny of seizure incidence, latency, and severity in genetically epilepsy prone rats.

The Genetically Epilepsy-Prone Rat (GEPR) is a widely studied model of epileptiform disorders. While there is considerable evidence that neurotransmitter abnormalities contribute to the unusual sensitivity of these animals to seizures, the possibility that seizure susceptibility may reflect developmental changes in the central nervous system has not been fully addressed. In the present study, 91 GEPR-9 pups were tested for incidence, latency and severity of an audiogenically induced seizure at 6, 9, 12, 15, 18, 21, 24, 27, 28, 29, or 30 days postpartum (1 test per pup) and retested at 60 days. Seizure incidence, latency, and severity were significantly greater on Days 27, 28, 29, and 30 than on all previous days. The first observation of running fits occurred in Day 18 pups and the first evidence of seizures occurred in Day 21 pups. When retested at Day 60, seizure incidence and severity were significantly greater than on initial tests while latency declined. The results suggest that seizure susceptibility in the GEPR-9 occurs as the result of developmental events in the CNS occurring on or shortly after Day 18 postpartum.

Unusual Red Blood Cell Sensitization Associated With Dyazide

The drugs hydrochlorothiazide and triamterene have both been implicated in in vivo red cell sensitization by the immune complex mechanism. The direct antiglobulin test in these instances generally is weakly positive due to complement components present on red blood cells. The red blood cell sensitization in this case was caused by the immune complex mechanism but was unusual in two respects. The direct antiglobulin test was strongly positive (3 + ), and only IgG was demonstrated on the patients red blood cells.