Impaired cognitive self-awareness mediates the association between alexithymia and excitation/inhibition balance in the pgACC.

BACKGROUND: Previous research showed that automatic emotion regulation is associated with activation of subcortical areas and subsequent feedforward processes to cortical areas. In contrast, cognitive awareness of emotions is mediated by negative feedback from cortical to subcortical areas. Pregenual anterior cingulate cortex (pgACC) is essential in the modulation of both affect and alexithymia. We considered the interplay between these two mechanisms in the pgACC and their relationship with alexithymia. METHOD: In 68 healthy participants (30 women, age = 26.15 ± 4.22) we tested associations of emotion processing and alexithymia with excitation/inhibition (E/I) balance represented as glutamate (Glu)/GABA in the pgACC measured via magnetic resonance spectroscopy in 7 T. RESULTS: Alexithymia was positively correlated with the Glu/GABA ratio (N = 41, p = 0.0393). Further, cognitive self-awareness showed an association with Glu/GABA (N = 52, p = 0.003), which was driven by a correlation with GABA. In contrast, emotion regulation was only correlated with glutamate levels in the pgACC (N = 49, p = 0.008). CONCLUSION: Our results corroborate the importance of the pgACC as a mediating region of alexithymia, reflected in an altered E/I balance. Furthermore, we could specify that this altered balance is linked to a GABA-related modulation of cognitive self-awareness of emotions.

Involuntary attentional capture by speech and non-speech deviations: a combined behavioral-event-related potential study.

This study applied an auditory distraction paradigm to investigate involuntary attention effects of unexpected deviations in speech and non-speech sounds on behavior (increase in response time and error rate) and event-related brain potentials (ΔN1/MMN and P3a). Our aim was to systematically compare identical speech sounds with physical vs. linguistic deviations and identical deviations (pitch) with speech vs. non-speech sounds in the same set of healthy volunteers. Sine tones and bi-syllabic pseudo-words were presented in a 2-alternative forced-choice paradigm with occasional phoneme deviants in pseudo-words, pitch deviants in pseudo-words, or pitch deviants in tones. Deviance-related ERP components were elicited in all conditions. Deviance-related negativities (ΔN1/MMN) differed in scalp distribution between phoneme and pitch deviants within phonemes, indicating that auditory deviance-detection partly operates in a deviance-specific manner. P3a as an indicator of attentional orienting was similar in all conditions, and was accompanied by behavioral indicators of distraction. Yet smaller behavioral effects and prolonged relative MMN-P3a latency were observed for pitch deviants within phonemes relative to the other two conditions. This suggests that the similarity and separability of task-relevant and task-irrelevant information is essential for the extent of attentional capture and distraction.

Intrathecal application of neuroectodermally converted stem cells into a mouse model of ALS: limited intraparenchymal migration and survival narrows therapeutic effects.

Stem and progenitor cells provide a promising therapeutic strategy for amyotrophic lateral sclerosis (ALS). To comparatively evaluate the therapeutic potentials of human bone marrow-derived mesodermal stromal cells (hMSCs) and umbilical cord blood cells (hUBCs) in ALS, we transplanted hMSCs and hUBCs and their neuroectodermal derivatives (hMSC-NSCs and hUBC-NSCs) into the ALS mouse model over-expressing the G93A mutant of the human SOD1 gene. We used a standardized protocol similar to clinical studies by performing a power calculation to estimate sample size prior to transplantation, matching the treatment groups for gender and hSOD-G93A gene content, and applying a novel method for directly injecting 100,000 cells into the CSF (the cisterna magna). Ten days after transplantation we found many cells within the subarachnoidal space ranging from frontal basal cisterns back to the cisterna magna, but only a few cells around the spinal cord. hMSCs and hMSC-NSCs were also located within the Purkinje cell layer. Intrathecal cell application did not affect survival times of mice compared to controls. Consistently, time of disease onset and first pareses, death weight, and motor neuron count in lumbar spinal cord did not vary between treatment groups. Interestingly, transplantation of hMSCs led to an increase of pre-symptomatic motor performance compared to controls in female animals. The negative outcome of the present study is most likely due to insufficient cell numbers within the affected brain regions (mainly the spinal cord). Further experiments defining the optimal cell dose, time point and route of application and particularly strategies to improve the homing of transplanted cells towards the CNS region of interest are warranted to define the therapeutic potential of mesodermal stem cells for the treatment of ALS.

Selective tuning of cortical sound-feature processing by language experience.

In 'quantity-languages', such as Japanese or Finnish, sound duration is linguistically relevant. We showed that quantity-language speakers were superior to speakers of a non-quantity language in discriminating the duration of even non-speech sounds. In contrast, there was no group difference in the discrimination of sound frequency. This result, obtained both by behavioural and neural indices at attentive and automatic levels of processing, indicates precise feature-specific tuning of the auditory-cortex functions by the mother tongue.

Developmental competence of oocytes after ICSI in the rhesus monkey.

Oocyte quantity and quality are critical to assisted reproductive technology (ART), yet few assessments beyond counting metaphase II (MII) oocytes exist. In this study, 30 +/- 2 oocytes per cycle were recovered from rhesus monkeys subjected to follicular stimulation with human gonadotrophins, of which 15 +/- 1 were MII. Oocyte quality was investigated by monitoring the developmental potential of oocytes subjected to intracytoplasmic sperm injection (ICSI). Despite uniform fertilization rates (71 +/- 4%), progression of embryos to blastocysts varied when expressed as a monthly average, from 20 to 85%, with lows from February to April and again in October, which could be attributed to developmental failure of a significant number of oocyte cohorts (14 of 55). Blastocyst rates, after elimination of failed cohorts, were uniform over time (59 +/- 4%). Neither culture conditions, the number of follicular stimulations, nor the individual sperm or oocyte donor were associated specifically with developmental failure, suggesting that intrinsic differences between stimulation cycles account for the observed variation in developmental potential. The in-vivo developmental competence of ICSI-produced embryos grown to blastocysts in vitro was also assessed. Two ongoing pregnancies and the birth of a normal female, 'Blastulina', represent landmarks in efforts to expand the use of ART in the rhesus monkey.

Fibronectin and laminin binding of urogenital and oral prevotella species.

88 strains of five Prevotella species--P. bivia, P. buccae, P. disiens, P. oralis, and P. oris--were examined for their fibronectin and laminin binding properties with the aid of latex particle agglutination assays. Beside single protein binding activities, all species showed strains that adhered to both fibronectin and laminin. The oral species, P. buccae, P. oralis, and P. oris were found to interact with laminin to a pronouncedly higher extent than with fibronectin. The urogenital species, P. bivia and P. disiens showed comparable activities of binding to fibronectin and laminin, with P. bivia exhibiting higher matrix protein binding rates than P. disiens. Within the oral species group, P. oralis showed a higher percentage of fibronectin and laminin reactive strains than did P. buccae and P. oris. The finding of species-related different binding properties may throw some light on the known differences in clinical relevance and pathogenicity of the urogenital species, P. bivia and P. disiens, but does so only in part concerning the oral species, P. buccae, P. oralis, and P. oris. Moreover, the observed differences in matrix protein binding of Prevotella species may have implications in chemotaxis and opsonization on the one hand and maintenance of colonization activities under antibiotic therapy on the other.

Speeded responses to audiovisual signal changes result from bimodal integration.

Integration of auditory and visual information was studied in humans detecting targets (i.e., location changes of the auditory, the visual, or both parts of a repetitively presented audiovisual stimulus). Behavioral results suggest that the time advantage to bimodal compared with unimodal targets was due to combined rather than separate processing of the auditory and the visual target information. Event-related brain potential results revealed strong audiovisual interactions supporting interactive and not independent coactivation models. The time course of this interaction suggests that the audiovisual integration occurred after low-level, sensory processing but well before the execution of the motor response.

Differential expression of progestin receptor isoforms in the hypothalamus, pituitary, and endometrium of rhesus macaques.

The progestin receptor exists in at least two isoforms: a long form (PR-B) and a short form (PR-A), which can be separated and detected with Western blot analysis. It has been suggested from in vitro transfection experiments that differential expression of the two isoforms may provide one mechanism for tissue specific actions of progesterone (P). However, more information from in vivo experimentation is needed. It has been reported that P down-regulates the expression of PR in the endometrium and pituitary of E primed macaques. However, PR protein and PR messenger RNA expression in the hypothalamus is maintained with P treatment of E-primed macaques. Thus, there is tissue-specific regulation of PR by its cognate ligand in the nonhuman primate. To gain insight into the tissue-specific regulation of PR by P, we questioned whether differential expression of the isoforms of PR exists in the endometrium, pituitary, and hypothalamus of rhesus monkeys. The expression of PR-A and PR-B was examined after E (28-30 days) and E + P (14 days E + 14 days E + P) treatment in the primate endometrium, pituitary, and hypothalamus. After E or E + P treatment, the levels of PR-A were 5 times higher than PR-B in the endometrium. PR-A was 1.6-fold higher than PR-B in the pituitary. In the hypothalamus, the ratio of A to B ranged from less than 1 (B exceeds A) to unity (A and B equimolar). There was no difference in the ratio of A to B between E-treated and E + P-treated groups in any tissue examined. These observations (a) provide further support of the hypothesis that differential expression of the isoforms of PR may subserve the tissue specific actions of P and (b) also suggest that P does not differentially affect the expression of the isoforms of its cognate receptor in the endometrium, pituitary, or hypothalamus.

Noncorneal astigmatism related to poly(methyl methacrylate) and plate-haptic silicone intraocular lenses.

PURPOSE: To evaluate noncorneal astigmatism after implantation of a one-piece, plate-haptic silicone or one-piece poly(methyl methacrylate) PMMA intraocular lens (IOL). SETTING: Klinik und Poliklinik für Augenheilkunde der Universität Regensburg, Germany. METHODS: After a follow-up of at least 3 months, the degree of postoperative noncorneal astigmatism was calculated using the data from an auto refractometer. Sixty patients were evaluated: 30 with silicone IOLs (Group A) and 30 with PMMA lenses (Group B). RESULTS: Mean noncorneal astigmatism in Group A was 0.78 diopter (D) +/- 0.51 (SD), which was statistically significantly higher than that in Group B (0.51 +/- 0.27 D) (P = .013). The highest noncorneal astigmatism, 2.32 D, occurred in Group A. CONCLUSIONS: Based on these findings, we recommend noncorneal astigmatism be considered in eyes with a one-piece, plate-haptic silicone IOL and postoperative astigmatism. A prospective study with a standardized capsulorhexis size is needed to ascertain whether this IOL-related noncorneal astigmatism is caused by capsular shrinkage, which may then be treatable with a laser capsulotomy of the anterior capsule.

Beta-endorphin, but not oxytocin, substance P or vasoactive-intestinal polypeptide, contributes to progesterone-induced prolactin secretion in monkeys.

Progesterone (P) stimulates prolactin secretion through a neural mechanism in estrogen (E)-primed female monkeys. Several peptides, including beta-endorphin (BE), oxytocin (OT), substance P (SP) and vasoactive intestinal polypeptide (VIP) are potential prolactin stimulatory factors and could mediate the effect of P. We hypothesized that the antagonism of a pivotal peptidergic neural system would block P-induced prolactin secretion and that the function of a pivotal peptidergic system would be altered by changes in gonadal steroid concentrations. Therefore it was of interest (1) to examine the effect of infusion of antagonists to these peptides on P-induced prolactin secretion, and (2) to determine BE, OT, SP and VIP levels in the hypothalamus of monkeys of various reproductive states. For the antagonist studies, female monkeys (n = 8) were spayed, adapted to a vest and tether remote sampling system and catheterized prior to antagonist challenges. E-primed monkeys received P injections 48 h prior to antagonist administration. Prolactin increased within 36-48 h of P injection. All antagonist challenges were administered in varying doses during the P-induced prolactin elevation and blood samples were collected every 10 min for prolactin determinations. The opiate antagonist, naloxone (n = 5), reduced serum prolactin in a dose-related manner with a mean IC50 of 1.5 +/- 0.6 micrograms/kg/min. The OT (n = 4), SP (n = 4) or VIP (n = 4) antagonists did not reduce serum prolactin in a dose-related manner. We previously reported that the hypothalamic content of OT is increased by ovarian hormones. To determine whether the hypothalamic content of BE, SP or VIP was related to gonadal status, the peptide levels in 4 hypothalamic regions of monkeys in various physiological states were measured. BE (ng/mg protein) in the medial basal hypothalamus (MBH) was significantly greater in adult females (17.7 +/- 6.9; n = 6) as compared to spayed females (0.6 +/- 0.2; n = 3) and juvenile females (1.8 +/- 1.1; n = 3). Hypothalamic content of SP in the preoptic area and mammillary bodies, but not the MBH, was significantly greater in gonadal intact females than spayed females. VIP content (pg/mg protein) was not significantly different between adult, spayed and juvenile females nor between adult and juvenile males in any hypothalamic area. Taken together these results support a pivotal role for BE in the neural regulation of P-induced prolactin secretion. The involvement of OT, SP, and VIP in a specific manner at the pituitary level is not indicated.

Immunohistochemical detection of progestin receptors in hypothalamic beta-endorphin and substance P neurons of steroid-treated monkeys.

Progesterone (P) acts in the central nervous system to increase prolactin secretion in estrogen (E)-primed female monkeys. beta-Endorphin (BE) and Substance P (SP) are two hypothalamic peptides which increase prolactin secretion when administered to rats and monkeys. Studies were performed to determine if P acts on these two potential prolactin-releasing systems. The presence of a nuclear steroid receptor defines the cell as a target for the cognate hormone. Therefore, the hypothalamic populations of BE and SP neurons were examined for the presence and regulation of nuclear progestin receptors (PR) in spayed, E-treated (28 days) and E + P-treated monkeys (14 days E + 14 days E + P). Hypothalamic blocks were prepared after perfusion fixation with 4% paraformaldehyde. Cryosectioning (10 mu m) was followed by double immunocytochemistry (ICC) for PR (black nuclear stain) and either BE or SP (brown cytoplasmic stain). Sections were processed for ICC at 100- or 200-mu m intervals through the hypothalamic block. Peptidergic neurons with and without PR were counted in each section. The E + P-treated monkeys exhibited a significant increase in serum prolactin. BE neurons were found only in the arcuate nucleus (ARC) and median eminence (ME). The colocalization of BE and PR equaled 2% in spayed controls, 21% in the E-treated group and 25% in the E + P-treated group. SP neurons were located in a dorsomedial hypothalamic (DMH) subpopulation which extended caudally under the mamillary nuclei and in a subpopulation located in the ARC and ME. Neither the DMH or submamillary SP neurons contained PR. The percent colocalization of SP and PR in the ARC/ME equaled 5, 26 and 10% in the spayed, E- and E + P-treated groups, respectively. The decrease in PR + SP colocalization with P treatment is probably due to a decrease in SP and not to a decrease in PR immunoreactivity. In summary, E treatment induced PR in BE and SP neurons. Addition of P to the E treatment did not alter the expression of PR in BE neurons, but PR colocalization decreased in SP neurons. Therefore, it is unlikely that SP neurons could transduce the action of P on prolactin secretion in primates, but BE neurons may play an intermediary role.

[Lens astigmatism in connection with implantation of a foldable one-piece silicone lens in a patient]. / Das Auftreten von Linsenastigmatismus in Zusammenhang mit Implantation einer faltbaren One-piece-Siliconlinse bei einem Patienten.

BACKGROUND: The use of one-piece plate-haptic Silicon lenses has become more frequent especially in combination with small incision cataract surgery. Different complications as before are to be expected. CASE REPORT: Six weeks after cataract surgery and implantation of a one-piece plate-haptic Silicon lens a lens astigmatism of 3.5 dpt was noted. The astigmatism occurred after successfully performed retinal detachment surgery in this eye. The development of the astigmatism was considered to be due to a capsular shrinkage of the anterior capsular ring. The retinal detachment surgery was performed with the use of SF6 gas, which is known as a factor for increasing inflammation. After a Nd: YAG incision of the anterior capsule the astigmatism disappeared immediately. CONCLUSION: Capsular shrinkage can induce a significant lens astigmatism in combination with soft one-piece plate-haptic Silicon lenses. Intraocular inflammation seems to play an important role. Astigmatism after implantation of one-piece plate-haptic Silicon lenses in combination with signs of capsular shrinkage can be explained by lens astigmatism only.

Effects of progesterone on prolactin, hypothalamic beta-endorphin, hypothalamic substance P, and midbrain serotonin in guinea pigs.

Unlike rats, but similar to primates, guinea pigs exhibit prolonged function of the corpus luteum and elevated progesterone secretion after ovulation. The gonadotropins, estrogen (E) and progesterone (P) have been examined throughout the guinea pig estrous cycle. However, neither prolactin secretion nor its regulation by steroid hormones has been characterized, perhaps due to the lack of a specific radioimmunoassay. beta-Endorphin (BE), substance P (SP), and serotonin (5-HT) increase prolactin secretion in rats and monkeys. BE and SP neurons in guinea pigs and 5-HT neurons in monkeys contain progestin receptors which could mediate neuroendocrine effects of steroid hormones. Therefore, the effects of E and P on prolactin, BE, SP, and 5-HT and its metabolite 5-HIAA were examined in guinea pigs which were ovariectomized, E treated (28 days), and E+P treated (14 days E+14 days E+P). The rat NB2 lymphoma cell line was used as a bioassay for serum prolactin. BE and SP levels were measured by radioimmunoassay in four hypothalamic areas: the preoptic region (POA), the mediobasal hypothalamus (MBH), the dorsomedial hypothalamus (DMH), and the mamillary bodies (MB). 5-HT and 5-HIAA were measured in the midbrain raphe area by high-pressure liquid chromatography. E alone had little effect on serum prolactin levels, but E+P significantly increased prolactin as compared with ovariectomized controls. The BE levels increased with E treatment and remained elevated with E+P treatment in MBH and POA. The BE content was stimulated in DMH and MB by E+P treatment and not with E alone. The SP content in MBH, DMH, and MB increased in E-treated guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Search for progestin receptors (PR) in prolactin-releasing peptidergic neurons: oxytocin neurons lack PR, but respond to gonadal steroids in monkeys.

Progesterone (P) increases PRL secretion in estrogen (E)-primed primates, but not by a direct action on lactotropes. Oxytocin is one of several hypothalamic hormones that stimulate PRL secretion. This study was conducted to determine whether oxytocin neurons directly mediate the action of P on PRL secretion. Hypothalamic sections from steroid-manipulated macaques were double immunolabeled for oxytocin and progestin receptors (PR). In addition, serum levels of oxytocin were measured in steroid-treated macaques, and hypothalamic levels of oxytocin were measured in monkeys under various physiological conditions. E treatment (28 days) of spayed monkeys caused a significant increase in the number of PR-positive neurons in the preoptic area, ventromedial nucleus, arcuate nucleus, and median eminence. Addition of P to the E treatment for the last 14 of 28 days did not change the number of PR-positive neurons in these areas. The number of PR-positive neurons was low and was unchanged by steroid treatment in the supraoptic and rostral paraventricular nuclei. Oxytocin neurons rarely contained PR regardless of anatomical location, steroid treatment, or fixation protocol. Serum oxytocin levels increased with E treatment and increased further with supplemental P treatment. The rostral and medial basal hypothalamic content of oxytocin was significantly higher in macaques with mature gonads. In conclusion, oxytocin neurons do not express nuclear PR and probably do not transcriptionally respond to P. However, gonadal steroids apparently affect the production and release of oxytocin in vivo. Thus, it is possible that oxytocin neurons transduce the action of P on PRL secretion via stimulatory neurotransmission from another PR-containing neural system.

[gamma-Irradiated ribosomes from Micrococcus radiodurans in a cell-free protein synthesizing system (author's transl)]. / gamma-Bestrahlte Ribosomen von Micrococcus radiodurans in einem System der zellfreien Proteinsynthese.

gamma-irradiation inactivation of isolated ribosomes of Micrococcus radiodurans was studied by examining poly U directed synthesis of polyphenylalanine. Ribosomes of M. radiodurans did not show significant gamma-radiation sensitivity up to a dose of approx. 11.6 k Gy. Cells of M. radiodurans take up more magnesium than E. coli cells unter the same conditions. The magnesium content of ribosomes of M. radiodurans was 18% higher than that of E. coli ribosomes. A possible relation between Mg2+-content and gamma-resistance is discussed.

A double-blind study of domperidone in the symptomatic treatment of chronic post-prandial upper gastrointestinal distress.

Oral domperidone (30 mg/day) or placebo tablets were given to 41 patients presenting with symptoms of chronic post-prandial dyspepsia, in a double blind study. The tablets were taken three times a day before meals. The first part of the study lasted four weeks and was followed by a second four week period in which domperidone was given on an open basis to all subjects. At the end of the double-blind phase all indices but one (bitter regurgitation) as well as the gastro-oesophageal reflux cluster had significantly improved on domperidone treatment while none had done so on placebo. During the subsequent open four weeks of domperidone all items improved in both study groups. No side effects were seen in any of the participants in the study.

[Protein synthesis with cell extracts of Micrococcus radiodurans (author's transl)]. / Proteinsynthese mit Zellextrakten von Micrococcus radiodurans.

Pure active ribosomes of cells of Micrococcus radiodurans could be obtained when cultivated in trypton, glucose and nutrient broth by adding natrium citrate. The optimal conditions for a cell-free protein synthesis were investigated at the (polyuridylic acid) dependent polyphenylalanine synthesis. When exchanging ribosomes and S100-fractions with the corresponding fractions of E. coli, we found that the enzyme fractions of M. radiodurans extremely inhibit the ribosomal activity. The incorporation rates in the cell-free system of M. radiodurans yield, at comparable conditions, in relation to E. coli under 10%.