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Inhibitory role of brain stem serotoninergic neuron system on thyroid function in rat.

Thyroid function was investigated in adult male rats following the use experimental procedures which inhibit the activity of serotoninergic neuron system. Pharmacological blockade of the biosynthesis of sertonin by repeated administration of para-chlorophenylalanine (pCPA), or interruption (by Halász knife) of the serotoninergic pathways of the brain stem which terminate on hypothalamic nuclei equally resulted in an augmentation of the following parameters of hypothalamo-hypophysial-thyroid activity: T/S ratio, pituitary and blood TSH levels and blood thyroxine concentration as well as TRH content of the hypothalamus. The results suggest that the central nervous serotoninergic neuron system plays an inhibitory role in the regulation of TSH secretion, presumably acting upon the hypothalamus, thereby inhibiting hypothalamic TRH secretion.

Animals

[Reversible dialytic encephalopathy after interruption of aluminium intake. 6 cases (author's transl)].

The cases presented with psychic troubles and repeated somnolence episodes accompanied by dysarthria in 5 cases, myoclonic jerks in 4 cases and epileptic seizures in 1 case. In all cases the EEG was disturbed. It showed symetrical, paroxystic, bilateral, monomorph slow activity with more or less frequent paroxysms. The average serum aluminium level was at 407 microgram/l in the acute phase, at 161 microgram/l in the remission phase and at 123 microgram/l three months later. After interruption of oral and dialytic aluminium intake the remission is maintained. However in 2 cases the transitory readministration of aluminium gel was followed by reversible recurrency. The role of both aluminium gel and dialysate aluminium as the origin of encephalopathy is discussed.

Aged

Mechanisms of B cell tolerance: I. Dynamic nature of the induction of hapten-specific unresponsiveness by hapten-conjugated pneumococcal polysaccharide.

Exposure of 2,4-dinitrophenyl (DNP)-hemocyanin-primed spleen cells to DNP-conjugated pneumococcal polysaccharide (DNP-S3) in vivo or in vitro renders such cells unresponsive to DNP-hemocyanin challenge following adoptive transfer. The unresponsiveness is hapten-specific, independent of the presence of T cells and adherent cells, and not due to either toxic effect of S3 or carry-over of tolerogenic amounts of cell-bound DNP-S3, and thus presumably represents a model of B cell tolerance. The degree of suppression induced depends upon the dose of the tolerogen and most strikingly on the duration of exposure of cells to the tolerogen. Thus 2 to 6 h exposure to DNP-S3 has an insignificant effect on anti-DNP responses, while 24 and 48 h exposures in vitro and in vivo are highly suppressive. Such a dynamic process of tolerance induction suggests a "multiple hit" phenomenon, implying the generation of suppressive signals by repeated cycles of tolerogen-receptor interactions. The process can be interrupted by removal of extracellular DNP-S3, although this does not reverse the unresponsiveness that has already been induced.

Animals

Cloned segment of Drosophila melanogaster rDNA containing new types of sequence insertion.

A cloned 14.3-kbase segment of Drosophila melanogaster rDNA (Dm207) is described in which only a 4-kbase region is homologous to a cloned 17-kbase rDNA repeating unit, Dm103; this 4-kbase region consists of part of the 28S rRNA gene and most but not all of the adjacent transcribed spacer that normally connects the 18S and 28S genes. The transcribed spacer in Dm207 is interrupted by a 2.2-kbase stretch of DNA that does not contain any 18S gene sequences. At the other end of the 4-kbase homology, the 28S gene is interrupted by an 8.1-kbase stretch of DNA at a position equivalent to the site of the 28S insertion found in the 17-kbase units. The question of whether the 2.2-kbase and 8.1-kbase interrupter segments in Dm207 derive from longer insertions into the transcribed spacer and 28S genes of a very long repeating unit (greater than or equal to 22 kbases) or represent a region of the chromosomal DNA into which a 4-kbase fragment of rDNA has been inserted is discussed.

Base Sequence

[Characteristics of the neuronal activity of structures of the hippocampal formation (subiculum)].

Spontaneous and evoked neuronal activity of subiculum was investigated in chronic unanaesthetized rabbits. Rhythmic components of two different types were observed in the spontaneous activity of 58% of units: 4.5-6.0 cps bursts (13%) and 2.0-3.8 cps (45%). Besides their basic frequency, these types of rhythmic activity were differentiated by several additional criteria. 63% of the cells responded to applied sensory stimuli, among which auditory stimuli were the most effective. Multimodal units were slightly more numerous (59%) than unimodal ones. In 50% of the recorded units responses were of tonic type, in 31%--of phasic type, and in 19%--specific on-off responses were observed. In majority of units with repeated stimulations relatively rapid process of habituation developed after a short incremental phase. Interruption of septal afferents resulted in disappearence of 4.5-6.0 cps (theta) bursts, in reduction in the number of tonic responses and in absence of habituation. Similarity of neuronal characteristics in the field CA1 and subiculum is discussed.

Animals

Dynamic mechanisms determine functional residual capacity in mice, Mus musculus.

Awake mice (22.6--32.6 g) were anesthetized intravenously during head-out body plethysmography. One minute after pentobarbital sodium anesthesia, tidal volume had fallen from 0.28 +/- 0.04 to 0.14 +/- 0.02 ml and frequency from 181 +/- 20 to 142 +/- 8. Functional residual capacity (FRC) decreased by 0.10 +/- 0.02 ml. Expiratory flow-volume curves were linear, highly repeatable, and submaximal over substantial portions of expiration in awake and anesthetized mice; and expiration was interrupted at substantial flows that abruptly fell to and crossed zero as inspiration interrupted relaxed expiration. FRC is maintained at a higher level in awake mice due to a higher tidal volume and frequency coupled with expiratory braking (persistent inspiratory muscle activity or increased glottal resistance). In anesthetized mice, the absence of braking, coupled with reductions in tidal volume and frequency and a prolonged expiratory period, leads to FRCs that approach relaxation volume (Vr). An equation in derived to express the difference between FRC and Vr in terms of the portion of tidal volume expired without braking, the slope of the linear portion of the expiratory flow-volume curve expressed as V/V, the time fraction of one respiratory cycle spent in unbraked expiration, and respiratory frequency.

Anesthesia

[Social consequences of birth in adolescents].

234 Austrian women gave birth to a child in the years 1972--74 before the age of 18. 95 of them were invited to an interview and interrogated about changes in their life-situation due to the birth. The general attitude was, if they could choose again the date of the first pregnancy they would prefer after 20 years. No correlation was found between early menarche and early sexual intercourse. For 60 of the women pregnancy was the reason for their marriage. Most of the young women had experience with contraceptives, but did not use them for different reasons. After the birth of the child most of them took the pill, but there are 11 women left without any contraception, exposing themselves to the risk of a repeat pregnancy. Young age at birth has an impact upon pre-vocational training: either through interruption of the training or through total discontinuation of their education. A possible solution of the present unsatisfactory situation for young pregnant women and their social problems are interdisciplinary projects for the guidance of adolescents in some centers in the USA.

Adolescent

Cytarabine and thioguanine for acute nonlymphocytic leukemia. Another look.

A modification of the protocol of cytarabine and thioguanine was used for remission induction in patients with acute nonlymphocytic leukemia. First, synchronization of the mitotically active leukemia cells was attempted by administering cytarabine alone in a dose of 5 mg/kg of body weight 24 hours prior to initiating daily therapy with both drugs. Second, in order to recover dormant leukemic cells into the proliferative pool, both drugs were continued without interruption and without regard to the suppression of the circulating leukocyte and platelet count until bone marrow aspirates, repeated daily if necessary, were free of leukemic blast cells. This usually resulted in severe but reversible bone marrow hypoplasia, and 16 of 21 patients (76%) so treated achieved complete hematologic remission.

Adolescent

Ovalbumin gene: evidence for a leader sequence in mRNA and DNA sequences at the exon-intron boundaries.

Selected regions of cloned EcoRI fragments of the chicken ovalbumin gene have been sequenced. The positions where the sequences coding for ovalbumin mRNA (ov-mRNA) are interrupted in the genome have been determined, and a previously unreported interruption in the DNA sequences coding for the 5' nontranslated region of the messenger has been discovered. Because directly repeated sequences are found at exon-intron boundaries, the nucleotide sequence alone cannot define unique excision-ligation points for the processing of a possible ov-mRNA precursor. However, the sequences in these boundary regions share common features; this leads to the proposal that there are, in fact, unique excision-ligation points common to all boundaries.

Animals

Population-scale disease-associated tandem repeat analysis reveals locus and ancestry-specific insights.

Tandem repeat (TR) expansions, including short TRs (motifs ≤6 bp) and variable number TRs (motifs >6 bp), underlie many monogenic disorders, with variable length and sequence influencing pathogenicity, penetrance, severity, and onset. Accurate genotype-phenotype correlation and disease prevalence estimation require characterization beyond repeat length. Here we present a population-scale analysis of 66 disease-associated TR loci using long-read assemblies from 2530 diverse haplotypes from 1265 unaffected donors. Integrating repeat length, motif composition, local ancestry, linkage disequilibrium, and phylogenetic analyses, we reveal extensive locus-, population-, and allele-specific variation shaping disease risk. Up to 8.5% of individuals carry expansions above established pathogenic thresholds, many containing interrupting motifs or sequence structures that attenuate pathogenicity. After excluding alleles from loci with uncertain disease association, non-pathogenic interrupted expansions, and carrier states inconsistent with inheritance patterns, ~4% carried expansions predicted to confer disease risk, largely at adult-onset loci with reduced penetrance. Ancestry-resolved analyses uncover population-specific TR architectures contributing to epidemiological disparities in repeat expansion disorders. Phylogenetic analyses identify conserved ancestral alleles and loci with recent instability. We describe variable linkage disequilibrium patterns and recombination signatures around specific disease-associated TR loci. Our findings emphasize integrating sequence, ancestry, and evolutionary context to understand the complex landscape of disease-associated TRs.

Humans

R loop mapping of the 18S and 28S sequences in the long and short repeating units of Drosophila melanogaster rDNA.

Cleavage of D. melanogaster rDNA with the Eco R1 restriction endonuclease reveals two major classes of repeating units: a long class of 17 kilobases (kb) and a short class of 11.4 kb. R loop mapping has been used to determine the topography of the sequences corresponding to the 18S and 28S rRNAs in both classes, including a cloned member (Dm103) of the long class. This mapping procedure derives from a novel reaction that we discovered between single-stranded RNA and homologous regions in duplex DNA molecules. In high formamide and at an elevated temperature, the RNA pairs with one of the two DNA strands in the region of homology to form an R loop in which one element is an RNA/DNA duplex and the other is single-stranded DNA (Figure 1). Mapping is accomplished by visualization of R loops in the electron microscope. The R loop map of Dm103 parallels that determined independently by Glover and Hogness (1977) from an analysis of its restriction fragments. Both maps indicate that the 28S rDNA in this cloned unit is divided into two blocks by a 5 kb insertion segment. R loop mapping of a population of long units obtained directly from the rDNA (that is, without cloning) has demonstrated that this interruption of the sequence coding for the 28S rRNA is a characteristic of the long class. By contrast, the 28S rDNA in the short units that we examined is not interrupted by an insertion segment. Otherwise, the R loop maps of the long and short units do not differ significantly. The two classes therefore correspond to repeating units that do (IN+) or do not (IN-) contain an insertion segment. Models for the transcription and function of these two classes of repeating units are discussed.

Animals

Biochemical treatment of precancerous oral lesions: the effectiveness of various analogues of retinoic acid.

Leukoplakia is neither a clinical, aetiological nor histopathological entity. Therefore treatment is difficult particularly in multifocal and advanced lesions. Since 1970, we have tested the therapeutic effect of different derivatives of all-trans-retinoic acid. The study includes 75 cases with homogeneous leukoplakia without or with minimal epithelial dysplasia. Over 60% of the cases treated showed positive early results. In follow-ups from 1 to 6 years about 45% of cases showed complete or partial remission. The rest showed relapses or even progression. In cases with recurrence without changes in the morphological characteristics, positive effects were achieved with 1 to 4 repeated courses of therapy. All derivatives of retinoic acid tested so far have shown undesirable side effects with systematic manifestations or local symptoms: interruption of treatment (4) or reduction of dosage (9) were unavoidable for that reason. Regarding the side effects, retinoic acid should only be given under clinical supervision. Of the derivates tested to date, aromatic retinoid seems to have the best curative potential in homogenic leukoplakia.

Humans

Prenatal diagnosis of polycystic kidneys and encephalocele (Meckel syndrome).

Two unrelated families are presented with repeated occurrences of a congenital syndrome of which the main stigmata were polycystic kidneys and occipital encephalocele (Meckel syndrome). Prenatal diagnosis, followed by interruption of pregnancy, was performed in one case. The diagnosis was based on an increase of amniotic alpha-fetoprotein (AFP), and on the mode of growth and cell types of cultured amniotic cells. In another similarly examined case the diagnosis was suspected, but the parents did not wish the pregnancy to be interrupted. The child was stillborn and malformed. AFP values are presented and discussed in relation to the observed malformations. Neural tube defects are associated with an increase of AFP in amniotic fluid, but, as in normal pregnancies, the values decrease with increasing gestational age. On the other hand, kidney malformations seem to be associated with AFP values which remain high or even increase with increasing gestational age.

Amniotic Fluid

Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production.

Although gonadotropin-releasing hormone (GnRH) is believed to mediate the hypothalamic control of pituitary gonadotropin secretion, continuous or repeated administration of GnRH or its agonist analogues has been shown to cause paradoxical antifertility effects in several species, including primates. GnRH-induced interruption of reproductive cycles and pregnancy is associated with diminished progesterone production, implying defective function of the corpus luteum. These luteolytic effects have been attributed to the well recognized desensitising actions of elevated luteinising hormone (LH) levels on ovarian LH receptors and steroidogenesis, subsequent to GnRH-induced gonadotropin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum progesterone levels during early pregnancy in rats, whereas a highly active GnRH analogue was effective in this regard. These observations suggested that GnRH and its agonist analogues, given in high or sustained doses, can exert a direct action on the ovary that is independent of the pituitary. This hypothesis was further supported by the ability of GnRH and its agonists to inhibit human chorionic gonadotropin (HCG)-induced ovarian and uterine weight gain in hypophysectomised rats and to delay the onset of puberty in intact female rats. Also, GnRH and its agonist analogues have recently been shown to inhibit steroidogenesis induced by follicle-stimulating hormone (FSH) in cultured granulosa cells, confirming the direct action of such peptides on the ovarian follicle. The marked inhibitory effects of GnRH and its agonists on corpus luteum function suggest that these compounds could exert direct actions by binding to specific receptors on luteal cells. The present experiments, which examine the effects of GnRH agonists on luteal steroidogenesis, demonstrate the existence of such actions and their mediation by specific high-affinity receptor sites present in luteal cell membranes.

Animals

Gene-sized DNA molecules of the Oxytricha macronucleus have the same terminal sequence.

The DNA in the macronucleus of the ciliated protozoan Oxytricha exists as small linear molecules with a number average size of about 3000 base pairs. Most, and possibly all, of these DNA molecules contain the same inverted terminal repeat sequence of approximately 26 base pairs. In addition to its terminal location, two inverted copies of this same sequence surround single-strand interruptions within these DNA molecules. This sequence arrangement may function in the processing of these molecules from large chromosomal precursors or in the subsequent replication of these small linear DNAs during cell reproduction.

Base Sequence

Smooth pursuit eye movements and attention in psychiatric patients.

The effects of two putative attention-engaging maneuvers on tracking performance were studied in three groups of subjects: inpatients (n = 19), outpatients (n = 19), and controls (n = 20). One method involved realerting subjects during tracking by repeating instructions to track carefully. The second method, a signal detection task incorporated into the tracking stimulus, required that subjects signal their perception of brief interruptions of the tracking light by pressing a hand-held button. The tracking performance of inpatients was significantly inferior to that of both outpatients and controls, whereas tracking performance of these two latter groups did not differ. Verbal realerting did not significantly improve tracking performance in any group; moreover, during the administration of these instructions there was an increase in tracking errors in inpatients. Inpatients also made more tracking errors than comparison groups during signal detection trials. Other subject factors of possible relevance to tracking performance, e.g., age, gender, and level of arousal, were found not to covary with tracking accuracy in a manner which would explain the observed group differences. It is unlikely that voluntary inattention is the basis for the observed impaired tracking in hospitalized psychiatric patients; the data are more consistent with an interpretation based on heightened distractibility or information overload in these patients.

Adolescent

Intramuscular 16-phenoxy PGE2 ester for pregnancy termination.

A new PGE2 derivative (16-phenoxy PGE2 methyl sulfonylamide sulprostone) was administered by the i.m. route to 48 women pregnancy in any of the three trimesters. The indications for pregnancy interruption were either serious medical problems in intact pregnancies (21 cases) or due to fetal death in utero (27 cases). Single doses of 500 micrograms were repeated every 4 hours in the former group or every 6 hours in the latter category for a maximum period of 24 hours. The treatment was successful in 81% of intact pregnancies and in 92.6% of fetal death cases with an overall mean induction interval of 12.9 hours. More than half the subjects did not experience any side effects apart from mild or moderate uterine colics. An overall mean of 1.4 episodes of vomiting or diarrhoea per induction trial was quite acceptable from the clinical point of view. The absence of serious complications in the group of critically sick women speaks in favor of the relative safety of the drug.

Abortifacient Agents

[Clinical-experimental studies on the behavior of the normal bladder blood vessels and of tumor vessels towards elevated intravesical pressure].

In 17 patients with tumours of the urinary bladder angiographies of the pelvis were carried out and then the angiography was repeated during an increase of the intravesical pressure to 60--120 mm Hg. In the normal, angiographically depictable vessels of the urinary bladder the blood circulation could not be interrupted by increased intravesical pressure. On the other hand, the pathological vessels of the tumours clearly reacted to an increase of the intravesical pressure. In 9 cases the circulation was completely interrupted, in 6 patients nearly all pathological vessels were compressed, and in 2 patients a clear reduction of the vessels visible before was reached. The different behaviour of normal and pathological vessels in our opinion is based on the inferior construction of the walls of the pathological vessels as well as on the lower blood pressure in the vessels of the tumour.

Aged