Working memory and fear conditioning

Previous studies of associative learning implicate higher-level cognitive processes in some forms of classical conditioning. An ongoing debate is concerned with the extent to which attention and awareness are necessary for trace but not delay eye-blink conditioning [Clark, R. E. & Squire, L. R. (1998) Science 280, 77-81; Lovibond, P. F. & Shanks, D. (2002) J. Exp. Psychol. Anim. Behav. Processes 28, 38-42]. In trace conditioning, a short interval is interposed between the termination of the conditioned stimulus (CS) and the onset of the unconditioned stimulus (US). In delay conditioning, the CS and US overlap. We here investigate the extent to which human classical fear conditioning depends on working memory. Subjects had to carry out an n-back task, requiring tracking an item 1 or 2 back in a sequentially presented list of numbers, while simultaneously being tested for their ability to associate auditory cues with shocks under a variety of conditions (single-cue versus differential; delay versus trace; no task versus 0-, 1-, and 2-back). Differential delay conditioning proved to be more resilient than differential trace conditioning but does show a reduction due to task interference similar in slope to that found in trace conditioning. Explicit knowledge of the stimulus contingency facilitates but does not guarantee trace conditioning. Only the single-cue delay protocol shows conditioning during the more difficult working memory task. Our findings suggest that the larger the cognitive demands on the system, the less likely conditioning occurs. A postexperimental questionnaire showed a positive correlation between conditioning and awareness for differential trace conditioning extinction.     

Severe exacerbation of hepatitis after short‐term corticosteroid therapy in a patient with “latent” chronic hepatitis B

Abstract: We present a case of severe exacerbation of hepatitis after short‐term corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy (CIPD) with “latent” chronic hepatitis B showing no HBV‐related antigens and antibodies. After corticosteroid pulse therapy for CIPD, the patient had severe exacerbation of hepatitis twice. Although she did not show any hepatitis B virus (HBV)‐related antigens or antibodies, sequences of HBV were detected in serum and liver by a nested polymerase chain reaction. A sequence analysis of HBV at the second exacerbation showed that the G‐to‐A point mutation at nucleotide 1896 that converted codon 28 from tryptophan (TGG) to a stop codon (TAG) in the precore region resulted in amino acid change, which has been frequently observed in fulminant hepatitis and severe hepatitis in Japan.     

Drug-induced Hypersensitivity Syndrome by EGFR-TKI in a Patient with Lung Cancer

An 83-years-old woman diagnosed with advanced Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma was administered afatinib as a first-line treatment. On Day 17, the patient presented with grade 3 diarrhea and a blood test analysis showed an increased inflammatory response. Afatinib treatment was discontinued on the same day. On Day 26, the patient displayed blepharedema and multiple irregular erythema covering her entire body. Drug-induced hypersensitivity syndrome (DIHS) was suspected, and the systemic administration of 30 mg/day prednisolone was administered. The symptoms subsided thereafter. A blood test analysis 3 weeks after onset revealed a reactivation of Human herpesvirus 6 (HHV-6) and a diagnosis of DIHS due to afatinib therapy was confirmed.     

Sinus escape-capture bigeminy and sinus extrasystolic bigeminy

Blocking conduction between the sinus node and the atria (SA block) can be responsible for symptomatic rhythm problems. However, in atrial escape-capture bigeminy with SA block, when atrial escape P waves originate in a site within or close to the sinus node, the diagnosis of SA block is not easy. Electrocardiograms were selected from 7 people with atrial bigeminy because (1) all atrial deflections (P waves) were almost the same in shape and in length of PR intervals, (2) comparatively long PP intervals alternated with comparatively short PP intervals, and (3) occasionally the atrial bigeminy changed to normal regular sinus rhythm in which 2 or more sinus P waves were found in succession. An attempt is made to clarify the mechanism for these cases. When regular sinus rhythm changed to bigeminal rhythm, the long PP interval introduced the bigeminy in 3 cases, indicating the presence of "sinus" escape-capture bigeminy; whereas the short PP interval introduced the bigeminy in the other 4 cases, indicating the presence of "sinus" extrasystolic bigeminy. In cases of sinus escape-capture bigeminy associated with SA block, the cases may occasionally be diagnosed wrongly as ordinary sinus arrhythmia not associated with SA block. Therefore, it seems that sinus escape-capture bigeminy is not so rare as is generally believed. Patients with SA block often require implantation of the artificial pacemaker. Thus, the authors believe that differentiation of sinus escape-capture bigeminy from other forms of "sinus" bigeminy is clinically important.     

In vivo gonadotropin-releasing hormone release and serum luteinizing hormone measurements in ovariectomized, estrogen-treated rhesus macaques

The push-pull perfusion technique was used to measure GnRH release in unanesthetized female rhesus macaques (Macaca mulatta) and to examine the dynamic relationship between GnRH release and LH levels during the estrogen-induced LH surge. Each ovariectomized macaque was anesthetized and stereotaxically fitted with a push-pull cannula directed into the median eminence (ME). After at least 1 week of recovery, each animal received an estradiol benzoate (E2B) injection (42 micrograms/kg BW) or an oil (OIL) injection and underwent push-pull perfusion of the ME and blood sampling for at least 5 h between 28 and 56 h postinjection. Continuous 10-min push-pull perfusates were collected and prepared for GnRH RIA. Peripheral venous blood samples were obtained either hourly or every 10 min, and serum LH levels were determined by Leydig cell bioassay. GnRH release was detectable and pulsatile in areas in or adjacent to the ME or arcuate nucleus. In eight OIL monkeys, GnRH pulses were regular (approximately one pulse every 60 min) and of low amplitude (14.7 +/- 12.0 pg), with a mean GnRH release rate of 4.0 +/- 1.7 pg/10 min. In five E2B-treated monkeys, GnRH release during the rising phase of the LH surge occurred as an apparent burst of high amplitude GnRH pulses. The mean GnRH release rate (37.5 +/- 17.9 pg/10 min) and mean GnRH pulse amplitude (170.0 +/- 90.0 pg) during the 5 h before the peak LH level in E2B-treated monkeys were greater than OIL values (P less than 0.025, mean release; P less than 0.05, mean amplitude). Within individual E2B-treated monkeys, hourly mean GnRH release rates were significantly correlated with LH levels during the ascending limb of the LH surge (r = 0.75 +/- 0.11; P less than 0.025). We have concluded that an increase in GnRH neurosecretion occurs in E2B-treated monkeys and that it is associated with generation of the LH surge. On the basis of our observations, we hypothesize that the primate hypothalamus, through changes in GnRH secretion, actively participates in the E2B-induced LH surge.     

Somatostatin-like immunoreactivity in mammalian thyroid glands: contents and partial characterization

Somatostatin (SRIF)-like immunoreactivity (SLI) in the thyroid glands of human and several animal species were compared, and the SLI peptides were characterized chromatographically and immunologically. All specimens were extracted with 2 M acetic acid, and the SLI content determined by RIA. The SLI concentrations in guinea pigs [34.3 +/- (SE) 4.8 ng/mg protein] and rabbits (9.4 +/- 0.8 ng/mg protein) were much greater than those in other mammals: dogs, rats, mice, and humans. On gel filtration of extracts of the guinea pig, rabbit and dog thyroids, the major peak of SLI (1.6 K SLI) coeluted with synthetic SRIF-14 (S-14). Two other forms of SLI ("big" SLI and 3 K SLI) were also detected, although their relative proportions to total SLI were small (2.3 to 8.2%). The 3 K SLI and 1.6 K SLI from guinea pig and rabbit thyroids contained peptides coeluting with synthetic SRIF-28 (S-28) and S-14, respectively, on reverse-phase high performance liquid chromatography. The dilution curves of the two molecular forms of SLI, i.e. 3 K SLI and 1.6 K SLI, were parallel to the displacement curves of S-28 and S-14 in the SRIF RIA. It is concluded 1) that the thyroid contents of SLI varied greatly from species to species, with the highest content being found in guinea pig thyroids; 2) that in guinea pigs, rabbits, and dogs, the predominant form of thyroid SLI is 1.6 K SLI; and 3) that the 3 K SLI and 1.6 K SLI peptides from guinea pig and rabbit thyroids are immunologically and chromatographically indistinguishable from S-28 and S-14, respectively.     

Usefulness of preheparin lipoprotein lipase mass as a parameter for predicting the efficacy of colestimide

This study was conducted to clarify the characteristics of colestimide responders. Forty-seven non-diabetic patients with high levels of low-density lipoprotein cholesterol (LDL-C) received colestimide at 3,000 mg/day and were followed up for 4 months. After 4 months, body weight was reduced but the change was not statistically significant. Total serum cholesterol (TC) and LDL-C levels significantly decreased from 280 to 232 mg/dl and from 195 to 150 mg/dl, respectively (p<0.01 versus before colestimide was administered). Serum triglyceride (TG) levels increased, but the change was not significant. Preheparin lipoprotein lipase mass (preheparin LPL mass) at baseline was significantly higher in colestimide responders (greater than a 20% decrease of LDL-C: n=28) than non-responders (76.2 ng/ml versus 50.3 ng/ml, p<0.05: n=19). Next, the subjects were divided into those with a high (n=33) and low (n=14) preheparin LPL mass at baseline. LDL-C levels were significantly decreased in patients with a high preheparin LPL mass while TG levels were significantly increased in patients with a low preheparin LPL mass. These results suggest that baseline preheparin LPL mass may be a marker of the response to colestimide.     

Rapid purification and characterization of human platelet glycoprotein V: the amino acid sequence contains leucine-rich repetitive modules as in glycoprotein Ib

Glycoprotein V (GPV) is a membrane-associated, 82 Kd platelet glycoprotein that is hydrolyzed during thrombin activation to yield 69 Kd fragment. We have developed a rapid and simple method for isolation of the protein from platelet extracts using a combination of gel permeation, anion-exchange, and lectin affinity chromatography. The partial amino acid sequence was determined by analysis of peptides generated by digestion of the S-carboxyamido-methylated protein with Achromobacter protease I or cyanogen bromide. The sequence shows a remarkable periodicity of leucine residues, which is homologous to the consensus sequence of a highly diversified protein super-family with a common repetitive module. Thrombin cleavage site was determined to be located at the C-terminal region of GPV by analysis of the products separated by sizing and reversed-phase high performance liquid chromatography. By lectin blot analysis, the existence of mucin-type carbohydrate chains was indicated, as well as the existence of asparagine-linked carbohydrate chains shown by the amino acid sequence analysis. From these data, we report a structural model of GPV that is analogous to glycoprotein Ib.     

Effects of changes in angiotensin converting enzyme activity on renin release: pretreatment with dexamethasone enhances a plasma renin activity response to captopril in normal subjects.

Healthy adults were given captopril (25 mg and 75 mg) po with or without dexamethasone (DXM) pretreatment (1 mg po 2 h before and simultaneously with the captopril). We determined the serum potassium and sodium concentrations, plasma prostaglandin E2 level, PRA, serum angiotensin converting enzyme (ACE) activity, and aldosterone level from 20 min before to 120 min after administration of captopril. DXM pretreatment stimulated the PRA response to captopril. This stimulation was suppressed by indomethacin. However, the administration of DXM did not induce a consistent rise in the prostaglandin E2 level. The administration of DXM induced a significant rise in the potassium concentration, but since simultaneous administration of indomethacin with captopril induced the suppression of PRA without affecting the potassium level, the PRA increase in response to captopril with DXM was not caused directly by the potassium increase. There were no significant differences in the PRA increase between 25 mg captopril and 75 mg captopril, or between DXM-25 mg captopril and DXM-75 mg captopril, though the inhibitions of ACE activity by captopril differed according to dose. The PRA increases, but not the captopril-induced inhibition of ACE activity, were significantly different between captopril alone and captopril with DXM pretreatment at either dose of captopril. Thus, the inhibition of ACE activity perhaps allows PRA to increase in response to captopril. These results suggest that the DXM stimulation of PRA may have been dependent on the inhibition of ACE activity by captopril.     

Correction to: Swallowing evaluation by the Kuchikara Taberu Balance Chart and videoendscopic examination reveals that respiratory conditions,chewing, and position are strongly related to dysphagia

This study focused on the Kuchikara Taberu Balance Chart (KTBC) as a tool for swallowing function evaluation. To clarify the relationship between videoendoscopic (VE) examination of swallowing function and the KTBC, we compared median KTBC scores with and without laryngeal penetration identified by VE. Sixty-five patients with a mean age of 84.3 ± 7.9 years were examined at the Towada City Hospital. The patients were classified into groups based on laryngeal penetration, including 28 patients with and 37 patients without penetration. We found no significant differences in patient backgrounds. The median KTBC score (interquartile range) was 36.5 (31–44.5) in the group with laryngeal penetration and 42 (35–48.5) in the group without penetration, but the scores were not significantly different (level of statistical significance at α = 0.0036 determined by the Bonferroni correction method) when compared with the Mann–Whitney U test (36.5 vs. 42, z = -2.33, p = 0.020). The median respiratory condition (3 vs. 4, z = − 3.23; p < 0.0036), oral preparatory and propulsive phases (3 vs. 4, z = − 2.96; p < 0.0036), and position and endurance (1 vs. 3, z = − 3.25; p < 0.0036) scores were significantly lower in the group with laryngeal penetration. This study revealed a correlation between laryngeal penetration confirmed by VE and KTBC scores. Consequently, respiratory condition, oral preparatory and propulsive phases, and position and endurance may be useful as tools for the assessment of swallowing. In particular, we recommend adding respiratory status to dysphagia screening.