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PubMed2001

Clinical applications of the 2nd generation assay for anti-TSH receptor antibodies in Graves' disease. Evaluation in patients with negative 1st generation test.

Detection of autoantibodies to the thyrotropin receptor by radioreceptor assays is largely requested in clinical practice for the diagnosis of Graves' disease and its differentiation from diffuse thyroid autonomy. Additionally, thyrotropin receptor antibodies (TRAb) measurement during antithyroid drug treatment can be useful to evaluate the risk of relapse after discontinuation of the therapy. Nevertheless, some patients affected by Graves' disease are TRAb-negative when a 1st generation assay is used. In this study we evaluated the diagnostic performance of a newly developed 2nd generation TRAb assay in 46 patients with Graves' disease with negative 1st generation TRAb assay results. A control group of 50 Graves' disease patients with positive 1st generation TRAb assay results, 50 patients with Hashimoto's thyroiditis and 50 patients with nodular goiter were also examined. Forty one of 46 patients with Graves' disease with negative 1st generation TRAb assay results showed a positive 2nd generation test. No differences were seen in control groups. In conclusion, the 2nd generation TRAb assay is more sensitive than the 1st generation test and should be used in clinical practice. Long-term prospective studies are needed to evaluate the prognostic role of the 2nd generation TRAb assay in Graves' disease.

Antibodies↗

PubMed1987

Generation 04 sodium slides and generation 04 reference fluid evaluated for use with the Ektachem 400 Analyzer.

Evaluation of a new generation of sodium slides and reference fluid for use with the Kodak Ektachem 400 Analyzer demonstrated improved performance in generation 04 over the previous generation 03 slide for sodium determinations. A decrease in between-replicate imprecision and a correction of the "serum" assigned values of the calibrators used to calibrate the slide used with the reference fluid account for the improvement. When generation 04/Ektachem results (y) were compared with results obtained with a Beckman ion-selective electrode (x), linear regression statistics were: slope = 0.88, y-intercept = 15.4 mmol/L, and Syx = 2.1 mmol/L. The average fixed bias in comparison with the Beckman electrode decreased from +1.9 mmol/L with generation 03 to -0.6 mmol/L with generation 04 materials. Random error is indicated by a decrease in Syx from 2.8 mmol/L for generation 03 to 2.1 mmol/L for generation 04. Application of Deming's regression, a more accurate portrayal of the generation 04 sodium data set, produces a slope of 1.0 and a y-intercept of -0.6 mmol/L.

Humans↗

PubMed1997

[Evaluation of one of the third generation reagents for anti-HCV antibody measurement in comparison with three second generation methods].

It is important to measure anti-HCV antibody(HCV.Ab) in blood to diagnose and treat viral hepatitis C patients. We evaluated one of the third generation reagents, Entymun-Test anti-HCV(Boehringer mannheim), which was developed to minimize false-positive reactions, and compared these results to findings obtained with three second generation tests for HCV.Ab. Coefficients of variation in the Entymum-Test assay were good(within-run, 1.1 approximately 1.8%; between-run, 2.5 approximately 7.5%). Four interfering substances(bilirubin C, bilirubin F, lipid and hemoglobin) hardly affected the HCV.Ab measurement. The HCV.Ab indices of healthy donors(n = 61) were distributed below the cut-off index(C.O.I). Sensitivity of the third generation test was the same as that of second generation tests, calculated from the results of dilution tests. Index of the dilution test in the third generation test formed a plateau until four-fold dilution, but there was no prozone phenomenon. Among the third generation test and three second generation tests, the former had the lowest positive percentage in serum HCV.Ab. Moreover, findings of HCV-RNA agreed more with the results of the third generation test among the four tests. As a result, the third generation test appeared to minimize false-positive results and improve specificity.

Evaluation Studies as Topic↗

PubMed2002

Self-generation as a means of maximizing learning in multiple sclerosis: an application of the generation effect.

OBJECTIVE: To examine the generation effect, the observation that items generated by subjects are better remembered than items provided, as a means of maximizing new learning in multiple sclerosis (MS). DESIGN: Prospective between-group design. SETTING: Private, nonprofit research facility. PARTICIPANTS: Population-based sample of 31 subjects with MS (MS group) and 17 healthy controls (control group), matched for age and education. INTERVENTION: Immediate, thirty-minute and 1-week assessments. MAIN OUTCOME MEASURES: Neuropsychologic tests assessing language, executive functioning, working memory, long-term memory, and the generation effect were administered. Recall and recognition of generation effect stimuli was tested immediately, 30 minutes, and 1-week after presentation. RESULTS: Recall and recognition of generated stimuli were significantly higher than provided stimuli across testing sessions. This effect was observed equally across the control and MS groups. Recall performance for generated stimuli correlated significantly with indices of episodic memory, information processing, and language but not executive control. Memory for the source of the information was deficient for generated words compared with provided words. CONCLUSIONS: The generation effect was present in MS and control subjects and may be a viable way of maximizing new learning in MS.

Adult↗

PubMed2006

Editing (out) generated study words in a recognition exclusion task: Effects of response signal delay and generation procedure.

Three experiments investigated participants' ability to exclude generated study words from "old" judgements on an exclusion task in which a response signal delay (RSD) was manipulated. In Experiment 1, words were generated by mentally conjoining components of two compound words, and a conjunction test condition was included (e.g., presentation of the lure checkpoint after studying checklist and needlepoint without generating the target). The exclusion error rate for generated words was higher than the conjunction error rate for a short RSD group but lower than the conjunction error rate for a long RSD group. The decrease in the familiarity effect across RSDs was extended to a conceptual cue generation procedure in Experiments 2 and 3, but an anagram generation procedure did not show similar evidence of recollection-based exclusions. The earliest indication of recollection-based editing of generated words occurred in a 2250-ms RSD (Experiment 3). An extension of a multi-factor transfer appropriate processing theory (deWinstanley, Bjork, & Bjork, 1996) of generation effects that incorporates influences of familiarity and recollection is advocated.

Attention↗

PubMed1987

Food-restricting first generation juvenile female hamsters (Mesocricetus auratus) affects sex ratio and growth of third generation offspring.

Female hamsters (Generation 1) were fed ad libitum or were food-restricted to 65-75% of the amount consumed by controls during their first 50 days of life. Subjects were mated at 91 days of age. Their offspring (Generation 2) were fed ad libitum throughout the experiment, and female offspring were also mated at 91 days of age. Generation 3 litters were monitored every fifth day from birth until Day 25 post partum for litter size, sex ratio, and pup weights. Although there were no significant differences in Generation 3 litter sizes at birth, litters descended from food-restricted Generation 1 females (Group R) were significantly smaller on Days 5-25 than litters descended from control Generation 1 females (Group A). Sex ratios remained significantly greater in Group A than in Group R litters from birth to Day 25 but did not vary over time, suggesting similar post-partum mortality rates for both male and female pups. Weights of Generation 3 male and female pups did not vary significantly within treatments at any time. Group A males weighed significantly more than Group R males from birth through Day 25, but weights of Group A and Group R females were always similar. Food restriction early in life may have long-term consequences on sex ratios of subsequent generations in hamsters.

Animals↗

PubMed1978

Generation of scratching. II. Nonregular regimes of generation.

1. The activity of muscle nerves and that of spinal interneurons from the L4 and L5 segments was recorded during fictitious scratching (5), which was evoked in decerebrate curarized cats by stimulation of the cervical spinal cord. In some experiments, rhythmical generation was disturbed by stimulation of the fifth lumbar dorsal root (DL5). 2. Excluding the very beginning of scratching, rhythmical generation was usually rather regular: fluctuations of the cycle duration were less than +/-5%. But changes in the stimulation strength, in the stimulating electrode position, and in the hindlimb position led to changes of the generation regime. In different regimes, the mean value of the cycle duration could differ by 20-30%. No correlation was found between mean durations of flexor and extensor phases for different regimes. 3. Rhythmical generation was possible only if the hindlimb was put to "scratch posture," i.e., deflected forward. Generation immediately stopped when the limb was deflected backward, and immediately started when it was returned to scratch posture. 4. In some experiments, stimulation of the cervical spinal cord first resulted in generation of slow oscillations with the temporal pattern typical of stepping (cycle duration about 500 ms, flexor and extensor phases being almost equal to each other). Then, during 5-20 cycles, gradual transition to a normal scratch cycle (about 250 ms) occurred mainly due to considerable shortening (5-10 times) of the extensor phase. In some experiments, considerable spontaneous variations of the flexor phase were observed, while the extensor phase was constant. 5. A single stimulus applied to DL5 considerably affected the cycle duration. Repetitive DL5 stimulation,with a rhythm close to that of scratching, resulted in synchronization of the spinal generator by the stimuli. 6. Spinal interneurons recorded during transition from slow oscillations to a normal scratch cycle only slightly changed phases of their activity in relation to the activity of motoneurons. 7. A hypothesis is advanced that generation of different kinds of limb movements is produced by one and the same central spinal mechanism which can operate in different regimes. The role of sensory input for operation of this mechanism is discussed.

Afferent Pathways↗

PubMed2004

[Intel random number generator-based true random number generator].

OBJECTIVE: To establish a true random number generator on the basis of certain Intel chips. METHODS: The random numbers were acquired by programming using Microsoft Visual C++ 6.0 via register reading from the random number generator (RNG) unit of an Intel 815 chipset-based computer with Intel Security Driver (ISD). RESULT: We tested the generator with 500 random numbers in NIST FIPS 140-1 and X(2) R-Squared test, and the result showed that the random number it generated satisfied the demand of independence and uniform distribution. We also compared the random numbers generated by Intel RNG-based true random number generator and those from the random number table statistically, by using the same amount of 7500 random numbers in the same value domain, which showed that the SD, SE and CV of Intel RNG-based random number generator were less than those of the random number table. The result of u test of two CVs revealed no significant difference between the two methods. CONCLUSION: Intel RNG-based random number generator can produce high-quality random numbers with good independence and uniform distribution, and solves some problems with random number table in acquisition of the random numbers.

Algorithms↗

PubMed2006

Third-generation vs a second-generation LED curing light: effect on Knoop microhardness.

Third-generation light-emitting diode (LED) curing lights use several different types of LEDs within the light to deliver a broader spectral output compared with the narrower spectral output of second-generation curing lights. This study determined the benefits of this broader spectral output. A third-generation LED curing light was modified so that the 4 peripheral LEDs, which provide the lower wavelengths, could be turned on or off, allowing the light to be used as a third- or a second-generation LED curing light. Twelve composites of A2 and lighter shades were packed into molds 2 mm deep with an internal diameter of 12 mm, and then irradiated for 20 seconds. A laboratory-grade spectroradiometer was used to ensure that all the specimens received the same irradiance and total energy (16.82 J/cm2) from the curing light in both the second- and third-generation modes. The results showed the benefits of using a broader spectrum third-generation LED curing light. This light produced composites that were as hard as when the narrower spectrum second-generation LED curing light was used (P < or = .01). In 7 of the 12 resin composites, the top surface was harder when the third-generation LED curing light was used (P < or = .01).

Bisphenol A-Glycidyl Methacrylate↗

PubMed1988

Activation of the human neutrophil by calcium-mobilizing ligands. II. Correlation of calcium, diacyl glycerol, and phosphatidic acid generation with superoxide anion generation.

Calcium and protein kinase C (Ca2+/phospholipid-dependent enzyme) have been proposed to act as signals in triggering superoxide anion (O2-) generation by neutrophils. We have probed the adequacy and necessity of calcium and diacylglycerol (DG), activators of protein kinase C, in eliciting O2- generation and degranulation. Activation of neutrophils by the ligand 10(-7) M fMet-Leu-Phe triggered elevation of cytosolic calcium (fura-2) and a rapid, biphasic increase in labeled DG in [14C]glycerol and [3H]arachidonate prelabeled cells. Buffering of the fMet-Leu-Phe-induced elevation of cytosolic calcium with MAPTAM (a cell permeant EGTA analogue) inhibited O2- generation by 90% and degranulation by 50%, concordant with a role of calcium in signaling. However, buffering the increase in calcium also decreased DG. Since phosphatidylinositol 4,5-bisphosphate breakdown in response to fMet-Leu-Phe was not inhibited and phosphatidic acid levels were enhanced in MAPTAM pretreated cells, the removal of calcium may enhance further DG metabolism. Thus, a requirement for calcium could not be differentiated from a requirement for DG, and the profound inhibition of O2- generation in the presence of MAPTAM may reflect removal of DG. Four stimuli, fMet-Leu-Phe, 10(-7) M leukotriene B4, 100 micrograms/ml concanavalin A, and 200 nM ionomycin elevated cytosolic calcium and triggered release of specific granules, but only fMet-Leu-Phe and concanavalin A triggered substantial O2- generation. Nevertheless, all four stimuli significantly increased labeled DG. Therefore, elevated DG and elevated calcium may be necessary but do not appear adequate to elicit O2- generation. Only fMet-Leu-Phe and concanavalin A triggered generation of phosphatidic acid (PA) together with DG. Correlation of O2- generation with PA may reflect a requirement for PA per se or for a specific pool of DG that can be further metabolized to PA.

Calcium↗

PubMed1993

Numbers of neurons in the developing principal sensory nucleus of the trigeminal nerve: enhanced survival of early-generated neurons over late-generated neurons.

The overproduction and subsequent death of neurons is a common phenomenon in the developing vertebrate central nervous system (CNS). We tested the hypothesis that the survival of a neuronal subpopulation is related to its time of origin. Neuronal survival was examined in a well-defined CNS structure, the principal sensory nucleus of the trigeminal nerve (PSN) of the rat. The changes in the total number of PSN neurons and in the numbers of early- and late-generated neurons (i.e., neurons heavily labeled by a single injection of [3H] thymidine on G12 or G14, respectively), between gestational day (G) 16 and postnatal day (P) 10 were determined. The total number of neurons in the PSN rose prenatally to a maximum of 40,600 on G18.5. The increase in neuronal number correlates to the period of migration. More than half of the neurons that successfully migrated to the PSN were lost by P10. The patterns for the changes in the numbers of early- and late-generated neurons were similar; however, there were significant differences between the two subpopulations. The maximum number of early-generated neurons (4,250) was attained on G18.2 and subsequently 58.9% of these neurons were lost. In contrast, the maximum number of late-generated neurons (5,050) was attained on G20.0 and 66.6% of these neurons were lost by P10. Therefore, it appears that the survivability of early generated neurons is greater than for late-generated neurons. This enhanced survivability presumably results from a competitive advantage that early-generated neurons have for forming synapses or gaining access to trophic factor(s) that are in limited supply.

Animals↗

PubMed1982

A two compartment model of the stepping generator: analysis of the roles of a stage-setter and a rhythm generator.

Recent studies on locomotion of the mesencephalic cat demonstrated that activation of the spinal stepping generator and the postural control system are dependent phenomena (Mori et al., 1978, 1980). This has motivated the construction of a new model of the stepping generator to account for interactions with the postural control system. The present model consists of two main compartments, the rhythm generator and the stage-setter. The rhythm generator generates rhythmic bursting discharges of extensor and flexor alpha motoneurons. The function of the stage-setter is to set and reset the excitability of extensor alpha motoneuron to a number of desired levels. This study analyzes interactions in this model between rhythm generating and postural control system. By adding a concept of "stage-setting" to the rhythm generator model, we succeed in simulating a variety of locomotor patterns observed in the mesencephalic cat, including "stepping automatism" (Mori et al., 1979).

Animals↗

PubMed1995

Contrasting influence of peplomycin and azelastine hydrochloride (Azeptin) on reactive oxygen generation in polymorphonuclear leukocytes, cytokine generation in lymphocytes, and collagen synthesis in fibroblasts.

The influence of peplomycin (PLM) and azelastine hydrochloride (Azeptin) on reactive oxygen (RO) and cytokine generation was examined in human peripheral blood mononuclear leukocytes, polymorphonuclear leukocytes (PMN), and rabbit alveolar macrophages (RAM). In addition, the influence of these drugs on DNA and collagen synthesis was investigated in human gingival and rabbit pulmonary fibroblasts. In vitro, PLM increased the FMLP- and PMA-induced chemiluminescence and superoxide (O2-) generation in human PMN and RAM in a dose-dependent manner. In contrast to PLM, Azeptin dose-dependently suppressed RO generation. Such contrasting actions of PLM and Azeptin were also observed in RAM and PMN obtained from rabbits treated with PLM or Azeptin. Even when human PMN were preincubated with 10-100 micrograms/ml of PLM, the increase in RO generation was negligible in the presence of 10(-5) M Azeptin in the culture medium. No increases in RO generation were observed in RAM or PMN obtained from rabbits that had received PLM (0.1 mg/kg per day) and Azeptin (0.04 mg/kg per day) concomitantly. PLM suppressed superoxide dismutase activity in RAM and human PMN, while Azeptin did not affect this activity. In vitro, PLM up-regulated the release of interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor both from human cells and from RAM and pulmonary fibroblasts. In the generation of these cytokines, Azeptin abrogated the up-regulatory action of PLM. PLM and Azeptin also had contrasting actions in [3H]thymidine and [3H]proline incorporation in human and rabbit fibroblasts. Furthermore, protein tyrosine phosphorylation, in particular that of a 115-kDa protein in human PMN, was suppressed by Azeptin and enhanced by PLM. These results seem to indicate that up-regulated RO and collagen generation are the causative factors of PLM-induced pulmonary fibrosis and that Azeptin may suppress the adverse effect.

Animals↗

PubMed1996

Chronic hepatitis C without anti-hepatitis C antibodies by second-generation assay. A clinicopathologic study and demonstration of the usefulness of a third-generation assay.

To study the clinicopathologic features of hepatitis C viremic patients negative for hepatitis C antibodies (anti-HCV) by current second-generation assay, we categorized 139 consecutive histologically verified patients with chronic non-A, non-B hepatitis into three groups: 121 (87%) were positive for second-generation anti-HCV (group A); 10 (7%) were negative for second-generation anti-HCV but positive for HCV RNA (group B); and 8 (6%) were negative for both antibodies and viremia (group C). Six (60%) of group B patients could be, further detected by a new third-generation assay, but none of group C patients was third-generation anti-HCV-positive. The demographic features, mean peak serum alanine aminotransferase levels, HCV genotype distribution, and histologic changes were comparable among the three groups. The study indicates that most patients with chronic hepatitis C in Taiwan could be identified by current second-generation assay, and viremic but antibody seronegative patients were clinicopathologically similar to the seropositives. Most patients of the latter group could be diagnosed by a third-generation assay, indicating the usefulness of this assay.

Chronic Disease↗

PubMed1986

Offset tuning curves generated by simultaneous masking are more finely tuned than those generated by forward masking.

The rapid ending of a tone produces an evoked potential which has different properties than that which is produced by the sudden onset of a tone. At the level of the round window, the offset N1 N2 follows the ending of the cochlear microphonic (CM) by approximately the same amount of time as does the onset N1 N2 to the onset of the CM. Both onset and offset responses are abolished with cochlear lesion. Continuous masking was used to generate tuning curves (TCs) from the NI-PI component of the evoked potential recorded from the round window of the gerbil. Those evoked potentials generated in response to the tone onset were complementary in appearance to those generated in response to the tone offset. TCs generated by continuous masking of the NI-PII component of the auditory brainstem response (ABR) of the gerbil show the same pattern. When it is generated by simultaneous masking, the midfrequency offset TC in the gerbil and mouse is W-shaped. It has two well tuned tips which occur at frequencies below and above that of the probe stimulus used to generate the TC. It also has an even better tuned peak occurring at or slightly above the probe stimulus frequency, which becomes sharper as the masker sound pressure level (SPL) is increased from 50 to over 80 dB. Because the midfrequency onset response is approximately 40 dB lower than the midfrequency offset response, probe stimuli for onset TCs are generally set at lower SPLs. When the onset probe stimulus is set to the same level as that of the offset probe, the Q10 dB of the offset TC may be up to 10 times the value of the Q10 dB of the onset TC. The offset TC generated in the CBA/J mouse by forward masking is quite different from that produced by simultaneous masking. Both forward and simultaneous conditions utilized a 40 ms duration tone to mask the PI-NI component of offset and onset ABRs of the mouse which were evoked by a 10 ms duration, 32 kHz tone, presented at an interstimulus interval of 160 ms. Forward masking (when compared with simultaneous masking) resulted in a more sharply tuned onset TC. But the offset TC was much less sharply tuned in the forward masking condition. This suggests that the offset response may reflect functions which are involved with fine tuning at moderate to high intensities in the presence of simultaneous sounds of similar spectral characteristics.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2006

Long-term outcomes in chronically hospitalized geriatric patients with schizophrenia: retrospective comparison of first generation and second generation antipsychotics.

INTRODUCTION: Some groups have reported the longitudinal course of elderly poor outcome schizophrenic patients to be characterized by progressive decline in cognitive functions and functional capacity. Although many of these patients experience minimal reduction of psychotic symptoms, there may be beneficial effects of antipsychotic treatments on cognitive functions and functional capacity. METHODS: This naturalistic study compared the longitudinal course of psychotic symptoms, cognitive functions and functional impairment in geriatric schizophrenic patients treated with first generation (N=97) or second generation (N=78) antipsychotic medications. Mixed effects linear regression analyses were used to examine the effects of treatment (first generation vs. second generation antipsychotic), time and treatment x time. RESULTS: Cognitive functions (Mini Mental State Examination time effect estimate=-.41, p<.001; ADAS-L Cog time effect estimate=.64, p<.001) and self-care skills (ADAS-L Self-Care time effect estimate=.65, p<.001) declined over time for the subject group as a whole and this decline was not modified by treatment with second generation antipsychotics relative to first generation antipsychotics. Similarly, second generation antipsychotic treatment produced no effect on the progressive worsening of negative symptom over time. CONCLUSION: This long-term naturalistic study of poor outcome geriatric patients with schizophrenia did not find atypical antipsychotics to produce any differential protective effect relative to typical antipsychotics on the long-term manifestations of symptoms, cognition and self-care in poor outcome geriatric schizophrenic patients.

Aged↗

PubMed1994

Significance of highly positive c22-3 "indeterminate" second-generation hepatitis C virus (HCV) recombinant immunoblot assay (RIBA) and resolution by third-generation HCV RIBA.

Second-generation recombinant immunoblot assay (RIBA) is widely used for the validation of anti-hepatitis C virus (HCV) antibody detection. The aims of this work were (i) to determine, in terms of liver disease and HCV replication, the significance of a peculiar "indeterminate" second-generation RIBA pattern characterized by the presence of high titers of antibodies directed to c22-3, a protein bearing core epitopes and (ii) to determine whether a more advanced version of the same strip assay, namely a third-generation RIBA, may solve the problem of such indeterminate patterns. Sixty patients for which c22-3 indeterminate second-generation RIBAs were highly positive were studied. Forty-two of them (70%) were immunocompromised. Serum transaminases were increased in 46 cases (77%), and HCV RNA was detected by PCR in 50 cases (83%). Third-generation RIBA remained highly positive c22 indeterminate for 9 patients (15%) but was positive for 51 (85%), mostly because of increased sensitivity for the detection of both anti-c100 and anti-c33c antibodies. These results suggest that third-generation RIBA may achieve resolution of most of these cases but that highly positive c22 indeterminate third-generation RIBA may persist when used with some patients with very low titers of anti-HCV nonstructural protein antibodies.

Adolescent↗

PubMed1989

Generation enhances semantic processing? The role of distinctiveness in the generation effect.

The goal of the present study was to investigate the locus of the memory advantage for words that are generated according to a nonsemantic rule (letter transposition) over words that are presented intact (read words). In the first two experiments, a category instance generation task was used to test the possibility that the semantic features of generated words are more readily available than those of read words. This possibility was not supported. In Experiment 3, generation effects were found to depend on the level of meaningfulness of words in recall, but not in recognition. In Experiment 4, a between-list design eliminated the generation effect found in recall, but did not affect the generation effect in recognition. Taken together, these findings suggest that generating a target according to a letter transposition rule enhances the distinctiveness of the word along a nonsemantic dimension.

Adult↗