[Mammography screening in Germany. Current results and future challenges]. / Mammographiescreening in Deutschland. Aktuelle Ergebnisse und zukünftige Herausforderungen.

The concept of mammography screening is based on the expectation that early diagnosis in a preclinical tumor stage enables less invasive treatment with a better prognosis than detection in advanced tumor stages. Mammography screening was implemented in European countries after results from large randomized controlled trials showed that regular screening led to a significant reduction in breast cancer mortality by 25-30 %. Recently, a major review of breast cancer screening services in Europe concluded that the benefits of screening clearly outweighed the disadvantages. In comparison to other European screening nations the German mammography screening program is relatively new. The challenge to prove the effectiveness by reduction in mortality still has to be solved. Continuous evaluation and optimization concerning the quality of structure, processes and results already confirm the high quality of the nationwide German screening services.

Galanin-1 receptor up-regulation mediates the excess colonic fluid production caused by infection with enteric pathogens.

Galanin is widely distributed in enteric nerve terminals lining the gastrointestinal tract. We previously showed that pathogenic Escherichia coli, but not normal commensal organisms, increase galanin-1 receptor expression by epithelial cells lining the colon (i.e., colonocytes). When present, galanin-1 receptor activation by ligand causes colonocyte Cl- secretion. We herein demonstrate that disparate pathogens including Salmonella typhimurium and Shigella flexerii also increase colonocyte galanin-1 receptor expression, whose activation is responsible for a principal component of the increased colonic fluid secretion observed. Although eliminating the GAL1R gene by homologous recombination does not alter basal colonic fluid secretion, removal of one or both alleles completely attenuates the increase in fluid secretion due to infection with enteric pathogens. Galanin-1 receptor up-regulation therefore represents a novel mechanism accounting for the increased colonic fluid secretion observed in infectious diarrhea due to several different pathogens.

Age-dependent differences in galanin-dependent colonic fluid secretion after infection with Salmonella typhimurium.

Epithelial cells lining the colon do not normally express galanin type 1 receptors (Gal1Rs). However, subsequent to infection with enteric pathogens such as Salmonella typhimurium, the Gal1R is rapidly upregulated in colonocytes where it contributes to the excess fluid production associated with diarrhoea. Humans infected with non-typhoid Salmonella respond differently according to age: infants develop diarrhoea but not bacteraemia and survive, while the elderly become bacteraemic and die. Thus the aim of this study was to determine if age-related differences exist in response to S typhimurium infection in mice, and whether these differences are due to altered Gal1R expression. Wild-type C57BL/6J mice that were 2 and 15 months old, as well as 2-month-old Gal1R knockout mice, were infected by gavage. Young wild-type mice expressed Gal1R in response to infection, had increased colonic fluid secretion, low rates of bacteraemia and survived. In contrast, 15-month-old wild-type mice expressed fewer Gal1Rs in response to infection, had attenuated increases in colonic fluid secretion, high rates of bacteraemia and died. A similar profile was noted in 2-month-old Gal1R knockout mice. Addition of polyethylene glycol to the drinking water of 15-month-old wild-type mice increased colonic fluid secretion and reduced rates of bacteraemia to those observed in 2-month-old wild-type mice and eliminated fatalities. The difference in response to S typhimurium infection with age may be due, at least in part, to decreased Gal1R expression and decreased amounts of colonic fluid secretion.

Stabilization of F-actin prevents cAMP-elicited Cl- secretion in T84 cells.

T84 cells, a human intestinal epithelial cell line, serve as a model of electrogenic Cl- secretion. We find that cAMP-elicited Cl- secretion in T84 cells is accompanied by a marked redistribution of F-actin in the basolateral portion of the cell. To prevent this F-actin redistribution and thereby assess its importance to Cl- secretion, we have defined simple conditions under which this model epithelium can be loaded with nitrobenzoxadiazole (NBD)-phallicidin. This reagent binds F-actin with high affinity thus stabilizing the F-actin cytoskeleton by preventing depolymerization, an event necessary for dynamic reordering of actin microfilaments. NBD-phallicidin loading is not cytotoxic as assessed by lactic dehydrogenase release, protein synthesis, transepithelial resistance, and the ability of the loaded cells to pump Na+ in an absorptive direction in response to the apical addition of a Na+ ionophore. However, cAMP-elicited redistribution of F-actin and the cAMP-elicited Cl- secretory response are both markedly impaired in NBD-phallicidin preloaded T84 cells. In contrast, the carbachol-elicited Cl- secretory response (Ca++ mediated) is not attenuated by NBD-phallicidin preloading nor is it accompanied by redistribution of F-actin. These findings suggest that the cAMP-elicited cytoskeletal redistribution we describe is an integral part of cAMP-elicited Cl- secretion in T84 cells.

Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers.

Toxin A of Clostridium difficile causes severe inflammatory enterocolitis in man and animals that appears to be mediated in part by acute inflammatory cells that migrate into the toxin A-exposed mucosa. To determine the direct effects of toxin A on intestinal epithelial permeability and structure in the absence of other modulating factors, we used cultured monolayers of a human intestinal epithelial cell line (T84). A toxin A concentration of 7 x 10(-1) micrograms/ml (3 x 10(-9) M) nearly abolished monolayer transepithelial resistance within 6-8 h. This marked permeability defect occurred while the monolayers were still confluent. Dual sodium-mannitol flux studies localized the permeability defect to the intercellular tight junction. Cytotoxicity assays and morphological evaluation using Nomarski optics and electron microscopy failed to demonstrate any evidence of cell damage at the time the maximum resistance response was observed. Fluorescent staining for F actin, however, revealed a marked decrease in fluorescent intensity in toxin-treated monolayers versus controls. These data show that toxin A can directly affect the barrier function of this model intestinal epithelium and initially does so by selectively enhancing tight junction permeability. Furthermore, cytoskeletal structure is markedly altered over the same time course, although the integrity of individual cells is maintained. Because the cytoskeleton of intestinal epithelial cells is known to be capable of regulating tight junction permeability, we speculate that the above effects of toxin A on epithelial barrier function result from alterations of the cytoskeleton.

Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function.

The mechanisms by which enteropathogenic Escherichia coli (EPEC), an important cause of diarrhea among infants in developing countries, induce symptoms are not defined. EPEC have a type III secretion system required for characteristic attaching and effacing changes that modify the cytoskeleton and apical surface of host cells. Infection of polarized intestinal epithelial cell monolayers by EPEC leads to a loss of transepithelial electrical resistance, which also requires the type III secretion system. We demonstrate here that EspF, a protein that is secreted by EPEC via the type III secretion system, is not required for quantitatively and qualitatively typical attaching and effacing lesion formation in intestinal epithelial cells. However, EspF is required in a dose-dependent fashion for the loss of transepithelial electrical resistance, for increased monolayer permeability, and for redistribution of the tight junction-associated protein occludin. Furthermore, the analysis of EPEC strains expressing EspF-adenylate cyclase fusion proteins indicates that EspF is translocated via the type III secretion system to the cytoplasm of host cells, a result confirmed by immunofluorescence microscopy. These studies suggest a novel role for EspF as an effector protein that disrupts intestinal barrier function without involvement in attaching and effacing lesion formation.

Pathogenic Escherichia coli increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression.

Galanin is widely distributed in enteric nerve terminals lining the human gastrointestinal (GI) tract. We have shown previously that galanin-1 receptors (Gal1-R) are expressed by epithelial cells lining the human GI tract, and upon activation cause Cl- secretion. Because expression of this receptor is transcriptionally regulated by nuclear factor-kappa B (NF-kappa B), which is activated by enteric pathogens as a part of the host epithelial response to infection, we investigated whether such bacterial pathogens could directly increase Gal1-R expression in the T84-cell model system. Pathogenic Escherichia coli, but not nonpathogenic E. coli, activate a p50/p65 NF-kappa B complex that binds to oligonucleotides corresponding to a recognition site located within the 5' flanking region of the human GAL1R gene. Pathogenic E. coli, but not normal commensal organisms, increase Gal1-R mRNA synthesis and [(125)I]galanin binding sites. Whereas galanin increases short-circuit current (Isc) approximately 5-fold in uninfected T84 cells, exposure to pathogenic, but not nonpathogenic, E. coli results in galanin increasing Isc approximately 20-fold. To confirm the validity of these in vitro observations, we also studied C57BL/6J mice infected with enterohemorrhagic E. coli (EHEC) by gavage. Infection caused a progressive increase in both NF-kappa B activation and Gal1-R expression, with maximal levels of both observed 3 days after gavage. Ussing chamber studies revealed that colons infected with EHEC, but not those exposed to normal colonic flora, markedly increased Isc in response to galanin. These data indicate that pathogen-induced increases in Gal1-R expression by epithelial cells lining the colon may represent a novel unifying pathway responsible for at least a portion of the excessive fluid secretion observed during infectious diarrhea.

Respiratory symptoms and bronchial responsiveness among cleaning and disinfecting workers in the food industry.

OBJECTIVES: To measure the levels of exposure to nitrogen trichloride (NCl3) and aldehydes among cleaning and disinfecting workers in the atmosphere of food industry plants during cleaning and disinfecting operations, and to examine how they relate to irritant and chronic respiratory symptoms-which are indices of pulmonary function-and bronchial hyperresponsiveness (BHR) to methacholine. METHODS: 175 exposed workers (M = 149; F = 26) recruited from 17 enterprises of the food industry (8 cattle, pig, and ovine slaughterhouses, 8 fowl slaughterhouses, and 1 catering firm) and 70 non-exposed workers (M = 52; F = 18) were examined. Concentration levels of NCl3 and aldhehydes were measured by personal sampling. Symptoms were assessed by means of a questionnaire and the methacholine bronchial challenge (MBC) test using an abbreviated method. Subjects were labelled MBC+ if forced expiratory volume in one second (FEV1) fell by 20% or more. The linear dose-response slope (DRS) was calculated as the percentage fall in FEV1 at last dose divided by the total dose administered. RESULTS: 277 air samples were taken in the 17 food industry plants. For a given plant and in a given workshop, the actual concentrations of chloramines, aldehydes, and quaternary ammonium compounds were measured with personal samplers during the different steps of the procedures. For each cleaner, a total exposure index Sigma was calculated. A statistically significant concentration-response relationship was found between eye, nasal, and throat symptoms of irritation--but not chronic respiratory symptoms--and exposure levels or exposure duration. No relation was found between BHR and exposure. CONCLUSIONS: These data show that cleaning and disinfecting workers in the food industry are at risk of developing eye, nasal, and throat irritation symptoms. Although NCl3 exposure does not seem to carry a risk of developing permanent BHR, the possibility of transient BHR cannot be ruled out entirely.

Coexistence of sudden cardiac death and end-stage heart failure in familial hypertrophic cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine the occurrence of sudden cardiac death or end-stage heart failure, two phases of the natural history of hypertrophic cardiomyopathy, in closely related relatives. BACKGROUND: Hypertrophic cardiomyopathy is a genetically transmitted cardiac disease with a particularly diverse clinical and morphologic spectrum. Premature death usually occurs either suddenly or as a result of progressive congestive heart failure. METHODS: We describe seven families with genetically transmitted hypertrophic cardiomyopathy that were studied with echocardiography or necropsy, or both, and were selected because they were known to include relatives who had incurred either premature sudden cardiac death or the end-stage phase of the disease. RESULTS: The seven families comprised 128 relatives; 26 died suddenly, and 9 developed end-stage heart failure (including 2 with heart transplantation) associated with left ventricular cavity enlargement, wall thinning or decreased contractility, alone or in combination, as well as loss of outflow obstruction. Patients who died suddenly did so at younger ages (23 +/- 10 years) than did patients who died or required heart transplantation in the end-stage phase of hypertrophic cardiomyopathy (42 +/- 8 years, p < 0.001). CONCLUSIONS: This study demonstrates that family members with hypertrophic cardiomyopathy, despite a common genetic substrate, may exhibit markedly diverse and distinct expressions of the natural history of their disease, which occur at widely separated periods of life.

Circadian variability in the occurrence of sudden cardiac death in patients with hypertrophic cardiomyopathy.

OBJECTIVES: The present study examined whether sudden death in patients with hypertrophic cardiomyopathy occurred with a particular pattern of frequency throughout the day. BACKGROUND: Previous investigators have shown a circadian distribution in the occurrence of sudden death and other cardiovascular events in patients with atherosclerotic coronary artery disease. Sudden death is also an important feature of the natural history of patients with hypertrophic cardiomyopathy. METHODS: The study group comprised 94 patients with a time of death (or cardiac arrest) that could be ascertained accurately to the nearest hour. This hourly distribution was analyzed by harmonic regression. RESULTS: Sudden death did not occur uniformly or randomly throughout the day. Rather, it was distributed in a bimodal pattern that conformed to a two-harmonic regression model. A disproportionate number of sudden deaths (43 [46%] of 94) occurred in the first peak in midmorning between 7 AM and 1 PM. The second peak of sudden death was less distinct but was in the early evening, between 8 PM and 10 PM. This periodicity in occurrence of sudden cardiac death was not evident for the days of the week or months of the year and, furthermore, did not appear to be influenced by other clinical variables, such as age, gender, severity of symptoms, subaortic gradient or left ventricular wall thickness. Sudden death occurred most commonly during periods of severe exertion (37 [39%] of 94). CONCLUSIONS: Sudden death in hypertrophic cardiomyopathy demonstrates a bimodal pattern of circadian variability over the 24-h day, with a prominent midmorning peak similar to that described in patients with coronary artery disease, and a less striking early-evening peak of occurrence. These findings suggest that temporally related physiologic changes, possibly in the electrical vulnerability of the myocardial substrate, may play a role in the sudden death of patients with hypertrophic cardiomyopathy.

Induction of silent myocardial ischemia with mental stress testing: relation to the triggers of ischemia during daily life activities and to ischemic functional severity.

OBJECTIVES: This study examined the relations among the triggers of ischemia during the activities of daily life, mental stress-induced ischemia in the laboratory and functional severity of ischemia on exercise testing. BACKGROUND: Myocardial ischemia is readily induced with exercise testing, but most episodes of ischemia in daily life occur during relatively sedentary activities. Although mental and emotional arousal are known to trigger myocardial ischemia, mental stress testing induces ischemia in only approximately 50% of patients with active coronary disease. It is not known whether such patients are particularly susceptible to nonexertional ischemia during daily activity. METHODS: We studied 45 men (mean age +/- SD 58 +/- 9 years) with coronary artery disease by means of 48-h Holter ambulatory electrocardiography for ST segment analysis and quantification of physical and mental activity with a structured diary system. These data were cross-tabulated with new left ventricular dyssynchrony (detected on two-dimensional echocardiography) induced by two mental stressors and by bicycle exercise. RESULTS: During mental stress testing, 24 patients (53%) (Group I) had a new wall motion abnormality; the other 21 patients (Group II) did not. The average wall motion dyssynchrony score increased from 1.20 +/- 0.29 to 1.34 +/- 0.36 (p = 0.001), but the increase was less than that with exercise stress (1.52 +/- 0.41, p = 0.001). The total duration of ischemia during sedentary activities was greater in Group I (22.9 +/- 24.5 min) than in Group II (3.6 +/- 3.9 min, p = 0.025). Group I had more ischemic events while sedentary (23 of 290 diary entries) than did Group II (8 of 256 diary entries, p = 0.015). The magnitude of dyssynchrony with mental stress and the number of mental stressors capable of triggering ischemia were related to severity of ischemia with exercise. CONCLUSIONS: Patients with ischemia during mental stress testing also have increased ischemia during sedentary activities in daily life. This finding may reflect greater functional severity of coronary artery disease or a propensity toward coronary vasoconstriction while sedentary.

Infection by bacterial pathogens expressing type III secretion decreases luciferase activity: ramifications for reporter gene studies.

Pathogenic microbes influence gene regulation in eukaryotic hosts. Reporter gene studies can define the roles of promoter regulatory sequences. The effect of pathogenic bacteria on reporter genes has not been examined. The aim of this study was to identify which reporter genes are reliable in studies concerning host gene regulation by bacterial pathogens expressing type III secretory systems. Human intestinal epithelial cells, T84, Caco-2 and HT-29, were transfected with plasmids containing luciferase (luc), chloramphenicol acetyltransferase (CAT) or beta-galactosidase (beta-gal) as reporter genes driven by the inducible interleukin-8 (IL-8) or constitutively active simian virus 40 (SV40) promoter. Cells were infected with enteropathogenic E. coli or Salmonella typhimurium, and the reporter activity was assessed. Luc activity significantly decreased following infection, regardless of the promoter. The activity of recombinant luc was nearly ablated by incubation with either EPEC or Salmonella in a cell-free system. Activity was partially preserved by protease inhibitors, and immunoblot analysis showed a decreased amount and molecular weight of recombinant luc, suggesting protein degradation. Neither beta-gal nor CAT activity was altered by infection. Disruption of type III secretion prevented the loss of luc activity. We conclude that CAT or beta-gal, but not luc, can be used as reliable reporter genes to assess the impact of pathogenic microbes, especially those expressing type III secretion on host cell gene regulation.

Clinical course of middle-aged asymptomatic patients with hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HC) may present a wide spectrum of clinical and morphologic manifestations. Although many aspects of the natural history of HC are understood, the initial presentation and subsequent clinical course of certain subgroups are not yet well defined. To further our understanding in this regard, 241 middle-aged patients with HC (aged 35 to 55 years) were analyzed. The vast majority of patients (210) had already experienced symptoms, whereas the remaining 31 initially presented with no or minimal symptoms and are the focus of this investigation; 29 of these were followed for greater than or equal to 2 years (range to 11.5 years, mean 8). A separate group of 30 moderately symptomatic age- and gender-matched patients with HC were selected as control subjects for morphologic comparisons. Of the 29 study patients with follow-up, 22 (76%) are presently free of important cardiac symptoms, but 3 showed progression of symptoms, and 4 have died suddenly. Annual mortality rate was 1.7%. Eighteen of the middle-aged asymptomatic patients with HC (58%) had localized left ventricular hypertrophy, usually involving only the anterior ventricular septum; in contrast, only 9 of the 30 symptomatic control subjects (30%) had such localized hypertrophy (p = 0.02). In conclusion, of those patients with HC who achieved middle-age without developing important cardiac symptoms, approximately 75% remained asymptomatic during the ensuing average 8-year follow-up. However, such patients are not protected in absolute terms from unfavorable clinical events (despite relatively mild left ventricular hypertrophy and in most cases absence of outflow obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Review article: Effector role of epithelia in inflammation--interaction with bacteria.

The common response to infection is infiltration of the affected tissue by inflammatory cells. It is now recognized that the epithelium plays a crucial role in this immunological process by producing an array of proinflammatory cytokines including interleukin-8, tumour necrosis factor-alpha, monocyte chemotactic protein-1, granulocyte-macrophage colony-stimulating factor, extractable nuclear antigen-78 and others. The response of the intestinal epithelium to bacterial pathogens is particularly intriguing because it is literally bathed by normal bacterial flora and bacterial components/products yet remains immunologically quiescent despite this potentially hostile environment. In contrast, when challenged by bacterial pathogens, intestinal epithelial cells exhibit a vigorous immunological response. Our laboratory has, therefore, focused on the immune response of intestinal epithelial cells when confronted by a specific bacterial pathogen, enteropathogenic Escherichia coli.

Alterations in the reinforcing efficacy of cocaine in adult rats following prenatal exposure to cocaine.

Adult male rats gestationally exposed to cocaine and nonexposed control offspring were examined for differences in operant responding for cocaine and sucrose reinforcement. Offspring were derived from dams that had received subcutaneous injections of 40 mg/kg/3cc cocaine hydrochloride daily on gestational Days 8-20 and nontreated control dams. Although no prenatal treatment differences were seen when the animals lever pressed for sucrose pellets on a progressive-ratio (PR) schedule, adult offspring prenatally exposed to cocaine were observed to exhibit an enhanced rate of cocaine intravenous self-administration on a fixed-ratio 5 (FR-5) schedule along with a marked decrease in break point on the PR reinforcement schedule. These results suggest that the reinforcing efficacy of cocaine may be reduced in animals with a prenatal history of cocaine exposure.

Further studies of the reinforcing effects of benztropine analogs in rhesus monkeys.

RATIONALE: Several halogenated analogs of benztropine (BZT) have previously been characterized as potent DA uptake inhibitors with behavioral profiles that indicate diminished psychomotor stimulant effects relative to cocaine. In a previous study using a fixed-ratio 10 schedule, two chloro-analogs (3'-Cl-BZT and 4'-Cl-BZT) maintained i.v. self-administration in monkeys but appeared to be weak positive reinforcers. OBJECTIVES: The present experiments were designed to test the hypothesis that 3'-Cl-BZT and 4'-Cl-BZT are relatively weak reinforcers by evaluating reinforcing effects under increased response requirements. To examine further the effect of this halogen substitution on self-administration, 3',4"-diCl-BZT was also evaluated for reinforcing effects. METHODS: Four rhesus monkeys self-administered cocaine (0.03 mg/kg per injection, i.v.) under a fixed-ratio 25 (FR25) schedule until stable responding was established. Saline, various doses of cocaine (0.003-0.2 mg/kg per injection), the BZT analogs (0.012-0.2 mg/kg per injection), GBR 12909 (0.012-0.2 mg/kg per injection), and compounds with known reinforcing effects (d-amphetamine, morphine, pentobarbital, ketamine) were then made available for self-administration. Various doses (0.01-0.3 mg/kg per injection) of the compounds that maintained self-administration under the FR schedule were then substituted for cocaine (0.1 mg/kg per injection) under progressive-ratio (PR) schedules. RESULTS: Reinforcing effects were evident under the FR schedule for 3'-Cl-BZT, 4'-Cl-BZT, GBR 12909, and the control compounds, but not by 3',4"-diCl-BZT. Results with the PR suggested that the rank order of these compounds for their effectiveness as reinforcers was cocaine > GBR 12909 > 3'-Cl-BZT = 4'-Cl-BZT >> 3',4"-diCl-BZT. CONCLUSIONS: This study confirms and extends previous results suggesting that compounds with high DAT affinity can have strong, moderate, weak, or no effectiveness as reinforcers. The mechanisms that may underlie this variation in reinforcing effectiveness of these DAT ligands remain to be established.

Galanin causes Cl- secretion in the human colon. Potential significance of inflammation-associated NF-kappa B activation on galanin-1 receptor expression and function.

Galanin is widely distributed in enteric nerves and nerve terminals throughout the gastrointestinal (GI) tract. Within the GI tract galanin is best known for its ability to alter smooth muscle contractility and regulate intestinal motility. However, recent studies also indicate that galanin can modulate epithelial ion transport. We previously showed that epithelial cells lining the human GI tract, including those of colonic origin, express Gal1 galanin receptors (Gal1-R). We herein demonstrate that epithelial cells lining the human colon only express Gal1-R receptors and do not express other galanin receptor subtypes. We previously showed that Gal1-R expression was transcriptionally regulated by the transcription factor NF-kappa B. Consistent with this transcription factor being activated in a number of inflammatory conditions, we show increased colonic Gal1-R expression in patients with colitis due to a variety of causes. To further evaluate the physiology of Gal1-R activation, we studied this receptor expressed by the human colon epithelial cell line T84. Gal1-R activation resulted in a dose-dependent increase in Cl- secretion; whereas infection of T84 cells with pathogens known to activate NF-kappa B augmented Gal1-R expression and Cl- secretion. Thus, galanin acts as a secretagogue in epithelial cells lining the human colon, with alterations in Gal1-R expression possibly playing an important role in the diarrhea associated with various inflammatory processes affecting the GI tract.

Disturbances in the performance of thermal discrimination tasks following cortical ablations in rats.

Previous studies of the effects of ablating the rat's somatosensory cortex on temperature discrimination have yielded negative results. Presently, it was assumed that (1) the rat's face might possess thermal acuity comparable to that found in highly sensitive skin regions of primates, (2) the rat's facial discriminative capacity for thermal differences might be more acute in a cool range well below normal room temperature (24 degrees C), and (3) by using more sensitive procedures and focusing on the effects of damage to the face areas in the rat's somatosensory cortex, disturbances in the capacity to make discriminations between cool stimuli might be revealed that previously went unnoticed. Results of experiments testing these assumptions indicated that rats can use their snouts to make discriminations of 1 degree C or less, that their acuity is better in the cool than in the warm range, and that somatosensory ablations produce moderate to severe disturbances in the capacity to discriminate between cool stimuli but only slight transitory disturbances in this capacity for warm stimuli. Additionally, the results suggest that the sensorimotor cortex may be involved in the rat's thermal discriminative capacity.

Effects of copper and vitamin B-6 deficiency on taste sensitivity in the rat: a signal detection analysis.

The effects of dietary copper and Vitamin B-6 deficiency on NaCl sensitivity in adult male rats were assessed in separate studies using a double-blind protocol, high-precision gustometry, computer-controlled go/no-go operant procedures and signal detection measures of sensitivity and responsivity. The dietary manipulations reduced plasma copper ion content to 40% of baseline levels in the copper deficient group and plasma 5'-pyridoxalphosphate content to 5% of baseline levels in the Vitamin B-6 deficient group and, as expected, altered hematocrit and hemoglobin levels in both groups. These metabolic changes resulted in increased NaCl preference in the Vitamin B-6 deficient group but did not alter sensitivity or responsivity to NaCl, and similar results were obtained in simple and complex taste discrimination tests. The present results demonstrate that dietary copper and Vitamin B-6 deficiencies do not result in altered taste sensitivity in the adult male rat.

Quality-specific differences in rat taste detection performance as a function of stimulus volume.

Taste detection performance for representatives of the four taste qualities as a function of stimulus volume (5 x 10(-4) to 1 x 1(-1) ml) was examined in rats using high-precision gustometry, computer-controlled operant procedures, nonparametric signal detection measures of sensitivity and responsivity, and blind control procedures. The overall sensitivity index was positively related to stimulus volume (rs = .60), with optimal detection performance attained with a 5 x 10(-3) ml stimulus volume for salty tastants and a 1 x 10(-2) ml stimulus volume for the other taste qualities. The overall responsivity index was inversely related to stimulus volume (rs = -.47), especially for sour and bitter tastants. These results are consistent with prior observations and demonstrate that operant methods using small tastant samples produce sensitive estimates of the rat's taste detection performance and response bias.