HLA DRB1*1503 allelic haplotype predominance and associated immunodysregulation in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic, relapsing, and remitting disease affecting primarily African American females of child bearing age. Familial aggregation of this disease suggests that at least part of the susceptibility for this disease is genetic, although environmental and hormonal influences are also likely to play a role. Early studies of genetic susceptibility to SLE revealed several of the major histocompatibility complex molecules, namely HLA DR, to be linked to SLE. Meta-analysis of genome scans has yielded loci significant for lupus patients, one of which includes the MHC region. Regulatory T cells are immunoregulatory cells that modulate activated immune cells. These cells play a large role in homeostasis of the immune responses and maintenance of immunologic tolerance, i.e., prevention of autoimmunity. Decreased numbers of regulatory T cells have been described in many autoimmune diseases, including systemic lupus erythematosus. Autoantibody production in systemic lupus erythematosus and the resulting immune complex formation and complex deposition into tissues are arguably the central core of immune dysregulation leading to disease manifestations and symptoms. Inability of the immune system to recognize and inhibit autoreactive immune cells in this particular autoimmune disease may be the result of inappropriate numbers and function of regulatory T cells. This study aims to characterize the immune cell population in patients from our community suffering from systemic lupus erythematosus and to prove that these patients exhibit a unique cellular profile compared to healthy age, race and gender matched control subjects. Surprisingly, our findings demonstrate that patients from the local Mississippi area exhibit increased proportions of CD25(+) FoxP3(+) regulatory T cells and CD25(+) FoxP3(-) T cells (of CD45(+) CD3(+) CD4(+) helper T cells) as compared to healthy controls. HLA tissue-typing of these lupus patients revealed a prominent subgroup (~30%) of patients possessing the HLA DRB1*1503 allele. The investigation of this subgroup demonstrated regulatory T cell composition similar to that of the total lupus group and to that of the non-HLA DRB1*1503 subgroup. Genetic analysis for molecular gene expression levels of various lupus-associated genes by real-time PCR demonstrated a unique profile as compared to healthy controls. Increased gene expression of FoxP3 together with decreased gene expression levels of GATA3, TNFAIP3, and TNFSF4 suggest that variations in gene products compared to healthy controls may be playing a role in the immune cell dysregulation and disproportionate CD25(+) FoxP3(+) regulatory T cells.

Effect of tricyclic antidepressants on taste responses in humans and gerbils.

One of the side effects of antidepressant pharmacotherapy reported clinically is impairment of the sense of taste. In this study, the taste effects of four tricyclic antidepressant compounds (clomipramine HCl, desipramine HCl, doxepin HCl, and imipramine HCl) were evaluated experimentally by topical application of the drugs to the tongue. Taste detection threshold concentrations for all four medications ranged from 0.1 mM to 0.2 mM in young persons but were elevated by as much as 7.71 times that in elderly individuals who were taking no concurrent medications. Each compound had a predominantly bitter taste with other qualities including metallic, sour, and sharp-pungent. In addition, each tricyclic antidepressant at concentrations from 1 mM to 5 mM blocked responses to a wide range of taste stimuli in both humans and gerbils. The differential suppression of other tastes by tricyclic antidepressants at the level of the taste receptors may contribute to the clinical reports of dysgeusia and hypogeusia.

Effect of medications on taste: example of amitriptyline HCl.

Use of medications is a major factor that contributes to taste losses in the elderly. Epidemiological studies suggest that community-dwelling elderly over the age of 65 use an average of 2.9 to 3.7 medications, and this number increases significantly for elderly living in retirement and nursing homes. The tricyclic antidepressant amitriptyline HCl is used by at least half a million people aged 65 years or more. In human studies performed here, amitriptyline HCl was found to have a bitter, unpleasant taste of its own. In addition, it blocked responses to other taste stimuli in both humans and gerbils. This blockage in humans was greater when amitriptyline HCl was applied continuously to the tongue than when it was applied intermittently. Continuous application of the drug affected all of the taste qualities to varying degrees, while intermittent application led to taste decrements only for salts. Electrophysiological studies in gerbils also revealed taste decrements after a short adaptation to amitriptyline HCl.

Effect of psychotropic drugs on taste responses in young and elderly persons.

The taste of six psychotropic drugs (amitriptyline HCl, clomipramine HCl, desipramine HCl, imipramine HCl, doxepin HCl, and trifluoperazine HCl) can be detected at concentrations of 0.1 mM or less in both young and elderly individuals. At concentrations 4 times higher than the detection thresholds, these drugs have bitter as well as other unpleasant taste properties. Oral exposure to these drugs not only induces a taste from the drug itself but also alters taste perception of other compounds such as NaCl and sucrose. These results indicate that both hypogeusia and dysgeusia may be induced by psychotropic medications.

Environmental pollutants alter taste responses in the gerbil.

Taste and smell are chemical senses that play a crucial role in food selection. Damage to taste and smell receptors can impair food intake, nutritional status, and survival. The purpose of this study was to determine the effects of 11 environmental pollutants (nine insecticides and two herbicides) on electrophysiological taste responses in the gerbil. Integrated chorda tympani (CT) recordings were obtained from gerbils to a range of tastants before and after a 4-min application of 1 of 11 environmental pollutants. The taste stimuli were: sodium chloride (100 mM), calcium chloride (300 mM), magnesium chloride (100 mM), HCl (10 mM), potassium chloride (500 mM), monosodium glutamate (MSG) (50 mM), sucrose (100 mM), fructose (300 mM), sodium saccharin (10 mM), quinine HCl (30 mM), and urea (2 M). The nine insecticides included organophosphorous, carbamate, and pyrethroid insecticides. The seven organophosphorous insecticides tested were: acephate, carbofuran, chlorpyrifos, chlorpyrifos oxon, demeton, malathion, and methamidophos. The carbamate insecticide carbaryl and the pyrethroid insecticide fenvalerate were also tested. Two herbicides, paraquat and glyphosate, were tested, and dose-response curves for each of these two herbicides were also determined. All of the 11 insecticides and herbicides had an effect on some of the taste stimuli tested. Application of 10 mM methamidophos exhibited the greatest amount of suppression on the 11 taste solutions. Each taste stimulus was significantly suppressed with the exception of 2 M urea. Herbicides paraquat and glyphosate also reduced responses to several tastants. These data indicate that environmental pollutants can modify taste responses in the gerbil.

Effect of lipid-derived second messengers on electrophysiological taste responses in the gerbil.

Integrated chorda tympani (CT) recordings were made to salty, sour, sweet, bitter, and glutamate tastants before and after a 4-min application of modulators of lipid-derived second messenger systems. The modulators included two membrane-permeable analogues of DAG, 1-oleoyl-2-acetyl glycerol (OAG) and dioctanoyl glycerol (DiC8); thapsigargin, which releases Ca++ from intracellular stores; ionomycin, a calcium ionophore; lanthanum chloride, an inorganic calcium channel blocker; nifedipine, a dihydropyridine calcium channel blocker; quinacrine diHCl, a phospholipase A2 antagonist; melittin, a phospholipase A2 agonist; and indomethacin, which decreases the release of prostaglandins by inhibiting the enzyme cyclo-oxygenase. The main findings were: OAG (125 microM) and DiC8 (100 microM) blocked the responses of several bitter compounds while enhancing the taste response to several sweeteners. Lanthanum chloride blocked all responses, which may be due to the fact that it blocks tight junctions. Quinacrine (1 mM) suppressed several bitter responses while enhancing the response to several sweeteners. The enhancement of sweet taste responses by DAG analogues suggests that there is cross-talk between the adenylate cyclase system and one (or more) pathways involving lipid-derived second messengers in taste cells.

Effect of pleasant odors on mood of males at midlife: comparison of African-American and European-American men.

The purpose of this study was to determine if daily use of colognes could elevate mood in middle-aged men. Sixty men ranging in age from 40 to 55 years participated in the study. Half were European-American and half were African-American. Mood ratings were obtained twice daily for 12 days using the Profile of Mood States questionnaire (POMS). The first 2 days of the experiment were used as baseline information to establish each man's mood prior to the administration of the colognes. The following 10 days of the study consisted of two conditions of 5 days each, the fragrance condition and the placebo condition. Main effects of condition (baseline, fragrance, placebo) were found for all POMS factors including tension, depression, anger, vigor, fatigue, and confusion, as well as for the Total Mood Disturbance score (TMD). The scores for the fragrance condition were significantly better than those for the baseline condition for tension, depression, anger, fatigue, and confusion factors, as well as for the TMD. Also, the scores for the fragrance condition were significantly better than those for the placebo condition for all factors and the TMD. There was a main effect for race, with European-American subjects having significantly worse scores for tension and fatigue and significantly better scores for depression than African-American subjects. An interaction was present between race and condition for the depression, vigor, and confusion factors. The main conclusion of this study was that use of pleasant odors improved the mood of males at midlife.

The effect of pleasant odors and hormone status on mood of women at midlife.

The effect of odors on the mood of 56 women ranging in age from 45 to 60 years was determined using the POMS (Profile of Mood States). The 56 subjects were divided into four groups of 14 subjects each on the basis of hormonal status. Group 1 consisted of 14 women who were still menstruating; group 2 consisted of 14 women who were no longer menstruating and taking estrogen; group 3 consisted of 14 women who were no longer menstruating and taking estrogen and progesterone; and, group 4 consisted of 14 women who were no longer menstruating and taking no hormone replacement. Use of pleasant odors significantly improved scores on tension, depression, and confusion factors. In addition, women using estrogen replacement with or without progesterone had better mood scores than those who did not, which is consistent with previous studies.

The effect of environmental odors emanating from commercial swine operations on the mood of nearby residents.

The effect of environmental odors emanating from large-scale hog operations on the mood of nearby residents was determined using the POMS (Profile of Mood States). The scores for six POMS factors and the TMD (total mood disturbance score) for 44 experimental subjects were compared to those of 44 control subjects who were matched according to gender, race, age, and years of education. The results indicated a significant difference between control and experimental subjects for all six POMS factors and the TMD. Persons living near the intensive swine operations who experienced the odors reported significantly more tension, more depression, more anger, less vigor, more fatigue, and more confusion than control subjects as measured by the POMS. Persons exposed to the odors also had more total mood disturbance than controls as determined by their ratings on the POMS. Both innate physiological responses and learned responses may play a role in the impairment of mood found here.

Modulators of the adenylate cyclase system can alter electrophysiological taste responses in gerbil.

The adenylate cyclase system has been implicated in taste transduction. The purpose of this study was to determine whether application of modulators of the adenylate cyclase system to the tongue alter taste responses. Integrated chorda tympani (CT) recordings were made in gerbils to bitter, sweet, salty, sour, and glutamate tastants before and after a 4-min application of four types of modulators of the adenylate cyclase system. The four types of modulators tested were: a) NaF, a compound that promotes dissociation of GTP binding protein; b) forskolin, a powerful stimulant of adenylate cyclase; c) 8-bromoadenosine 3' :5'-cyclic monophosphate sodium salt (8BrcAMP) and N6,2'-O-dibutyryl-adenosine 3' :5'-cyclic monophosphate sodium salt (DBcAMP), two membrane permeable forms of cAMP; and d) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) and N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide dihydrochloride) (H-8), which are protein kinase inhibitors. The tast compounds tested were: NaCl (30 mM), monosodium glutamate-MSG (50 mM), sucrose (30 mM), HCl (5 mM and 10 mM), KCl (300 mM), quinine HCl (30 mM), MgCl2 (30 mM), erythromycin (0.7 mM and 1 mM), HCl (5 mM and 10 mM), and urea (2 M). The main findings were as follows. NaF (20 mM) significantly inhibited responses to bitter compounds up to 35% and enhanced the response to sucrose by 30%. NaCl (20 mM), used as a control for NaF, inhibited most responses up to 78% with no enhancement of sucrose as seen with NaF. 8BrcAMP (1.16 mM) reduced the responses to bitter-tasting quinine HCl, MgCl2, and erythromycin but not to urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of modulators of the adenylate cyclase system on sweet electrophysiological taste responses in gerbil.

The adenylate cyclase system has been implicated in sweet taste transduction. The purpose of this study was to determine whether application of modulators of the adenylate cyclase system to the tongue alters sweet taste responses. Integrated chorda tympani (CT) recordings were made in gerbils to sweet tastants before and after a 4-min application of four types of modulators of the adenylate cyclase system. The four types of modulators tested were: a) NaF, a compound that promotes dissociation of GTP-binding protein; b) forskolin, a powerful stimulant of adenylate cyclase; c) 8-bromoadenosine 3' :5'-cyclic monophosphate sodium salt (8BrcAMP) and N6,2'-O-dibutyryladenosine 3' :5'-cyclic monophosphate sodium salt (DBcAMP), two membrane permeable forms of cAMP; and d) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) and N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide dihydrochloride) (H-8), which are protein kinase inhibitors. The sweet compounds tested were: sucrose (30 mM and 100 mM), glucose (300 mM), fructose (300 mM), maltitol (150 mM and 300 mM), mannitol (300 mM and 500 mM), sodium saccharin (10 mM), D-tryptophan (6.5 mM), dulcin (0.88 mM, 1.75 mM, and 3.5 mM), and stevioside (0.55 mM and 1.1 mM). NaCl (30 mM and 100 mM) and KCl (300 mM and 500 mM) were used as control stimuli. The main findings were as follows. Application of NaF (20 mM) for 4 min as a rinse significantly enhanced all of the sweet compounds by at least 23%, except for 10 mM sodium saccharin and 6.5 mM D-tryptophan, while all control compounds were suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Astringent compounds suppress taste responses in gerbil.

Astringent tastes are generally considered those that induce long-lasting puckering and drying sensations on the tongue and membranes of the oral cavity. Electrophysiological recordings were made here from the whole chorda tympani nerve in gerbil to understand the interactive effect of astringent-tasting molecules with a broad spectrum of tastants including mono- and divalent salts, bitter compounds, acids, and sweeteners. The astringent tasting compounds were tannic acid (24 mM at pH's 2.9 and 5.5), aluminum ammonium sulfate (30 mM), aluminum potassium sulfate (10 mM) and gallic acid (30 mM). Hydrochloric acid (1 mM, pH 2.9) was also tested to control for acidity, since aqueous solutions of astringent-tasting compounds are acidic. Adaptation of the tongue to tannic acid (24 mM) at both pH 2.9 and 5.5 markedly inhibited responses elicited by salts, acids, sweeteners, and bitter-tasting compounds. The degree of the inhibition at these two pH values is about the same which suggests that tannic acid itself (as opposed to acidity) may produce this inhibition. Chorda tympani responses to sweeteners were completely suppressed by tannic acid; responses to KCl, NH4Cl, and urea were the least suppressed. The aluminum salts also inhibited the chorda tympani responses to all stimuli tested. Gallic acid, which is weakly astringent, had minimal effects on the chorda tympani responses to the test compounds. These data suggest that both tannic acid and the aluminum salts inhibit a variety of transport pathways and receptors in taste cells for a broad spectrum of tastants. The inhibition of some of these pathways may contribute to the astringent taste sensation.

Chorda tympani and lingual nerve responses to astringent compounds in rodents.

A wide variety of compounds in foods and beverages produce astringent sensations when introduced into the oral cavity. There is controversy, however, whether "astringency," with its associated puckering and drying sensations, is a fundamental taste quality or is a tactile sensation. To address this issue, electrophysiological recordings were made from the gerbil chorda tympani nerve and the rat lingual nerve. The chorda tympani nerve transmits taste information from the anterior 2/3 of the tongue, whereas the lingual nerve transmits tactile, thermal and pain sensations from the anterior 2/3 of the tongue. The astringent compounds tested were: tannic acid, tartaric acid, gallic acid, aluminum ammonium sulfate and aluminum potassium sulfate. Tannic acid, tartaric acid, and gallic acids were tested at concentrations up to 120 mM over a pH range from approximately 2 to 6. The aluminum salts were tested at concentrations up to 160 mM only at low pH's. All compounds rapidly (and at lower concentrations, reversibly) stimulate the chorda tympani nerve in a concentration-dependent manner at all pH's tested. The rapidity and reversibility of the chorda tympani responses suggest that astringent-tasting compounds interact directly with taste cells rather than indirectly by precipitating salivary proteins. At pH 6, tannic acid, tartaric acid, and gallic acid all elicit robust chorda tympani responses, implying that the ionized forms of these compounds produce taste sensations. None of these compounds stimulate lingual nerves over the same concentration and pH ranges used in the chorda tympani experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of amiloride analogs on taste responses in gerbil.

Amiloride analogs that were designed to inhibit three types of Na+ transport systems (the epithelial Na+ channel, the Na+/H+ antiporter, and the Na+/Ca++ exchanger) were applied to the tongue of the gerbil to determine their effects of electrophysiological taste responses to NaCl, CaCl2, sucrose, and glutamic acid. The pattern of responses from the chorda tympani nerve indicates that the taste of NaCl is almost totally accounted for by the epithelial Na+ channel. Phenamil, an amiloride analog which specifically blocks the epithelial Na+ channel at low concentrations, suppressed the taste responses to 0.03 M NaCl by 97%. The pattern of responses also indicates that the Na+/H+ antiporter and the Na+/Ca2+ exchanger do not mediate salt taste in the gerbil. None of the amiloride analogs blocked taste responses to CaCl2, sucrose, or glutamic acid. It is concluded that the salty taste of NaCl in the gerbil is almost totally mediated by the epithelial Na+ channel, and the kinetics of this channel are identical to amiloride-sensitive sodium channels in other systems.

Inhibition of taste responses to Na+ salts by epithelial Na+ channel blockers in gerbil.

The Na+ transport inhibitor amiloride blocks taste responses to NaCl by 60-70%. The purpose of the present study was to determine if greater inhibition could be achieved with three potent amiloride analogs that are specific for the epithelial Na+ channel: phenamil, 2',4'-dimethylbenzamil, and 3',4'-dichlorobenzamil. Application of phenamil (100 microM) to the anterior tongue blocked integrated responses to NaCl from the chorda tympani nerve by 98.04%, but had no significant effect on sucrose or NH4Cl. This finding suggests that the epithelial Na+ channel alone transduces the taste of NaCl in gerbil. The residual 30-40% of the response that is not blocked by amiloride can simply be explained by the fact that amiloride is less potent than phenamil. On average, 100 microM phenamil blocked responses to Na+ salts with a variety of anions by 94.2%; 100 microM 2',4'-dimethylbenzamil, by 89.83%; and 100 microM 3',4'-dichlorobenzamil, by 72.56%. Small residual responses to salts of glutamate and phosphate were not eliminated by the amiloride analogs; this suggests that other transduction mechanisms may account for a small portion of taste responses for these salts in the gerbil.

Evaluación de posibles métodos internacionales de referencia para la prueba de inhibición de la hemaglutinación para la rubéola: informe de un estudio en colaboración / Evaluation of candidate international reference methods for the rubella hemagglutination inhibition test: report of a collaborative study

Existen varios procedimientos en todo el mundo para efectuar la prueba de la inhibición de la hemaglutinación (IH) para detectar anticuerpos de la rubéola en sueros humanos. En este artículo se presenta un proyecto internacional patrocinado por la OMS para seleccionar uno de dichos procedimientos como método internacional de referencia (AU)

Evaluación de posibles metodos internaciónales de referencia para la prueba de inhibición de la hemaglutinación para la rubéola: informe de un estudio en colaboración / Evaluation of candidate international reference methods for rubella hemagglutination inhibition test: report of a collaborative study

Existen varios procedimientos en todo el mundo para efectuar la prueba de la inhibición de la hemaglutinación (IH) para detectar anticuerpos de la rubéola en sueros humanos. En este artículo se presenta un proyecto internacional de investigación patrocinado por la OMS para seleccionar uno de dichos procedimientos como método internacional de referencia

The development by the Centers for Disease Control of a specification for streptococcal serogrouping kits and its application to Streptex and to the Phadebact Streptococcus Test.

A Centers for Disease Control (CDC) specification for evaluating commercially produced streptococcal agglutination reagents was developed and used to test Streptex and Phadebact Streptococcus Test kits. Evaluation methods and performance requirements were based on product claims made in the package labelling. Except for the reagent for Streptococcus group D, reagents of both systems identified 100% of the blind-coded reference strains when follow-up methods were done according to the manufacturers' directions. Streptex group D reagent did not identify all group D strains, but the manufacturer instructed the user to test with other methods in certain circumstances. The interaction of personnel of the Center for Infectious Diseases (CID), CDC, with commercial producers and consumers in a pre-market evaluation program is described.