Method for the cross protection of mice in studying the antigenic variability of the influenza virus

A modification of the method of cross protection of mice was developed for the study of influenza virus antigenic drift. This modification does not require a pre-adaptation of the virus to mouse lungs. The experiments of cross protection of immune animals carried out by the modified method demonstrated antigenic variability of the influenza A virus strains (H3N2) isolated in 1968-1983. Immunologically significant differences between influenza A/Hong Kong/68/ and A/Victoria/36/72 virus strains were detected. Subsequently, with isolation of more influenza virus strains immunologically significant differences were found between A/Victoria/36/72 and A/Leningrad/42/75 (an analogue of A/Scotland/840/74) strains, A/Leningrad/42/75 and A/Leningrad/399/76 (an analogue of A/Victoria/3/75) strains. The differences between influenza A/Texas/1/77 and A/Leningrad/527/80 (an analogue of A/Bangkok/1/79), A/Leningrad/385/80 (an analogue of A/Bangkok/1/79), and A/Leningrad/50/83, (an analogue of A/Philippines/2/82) strains were not immunologically significant.     

Polymorphism of the promoter of the HLA-A locus

Of the first 350 bases upstream of the ATG signal sequences were obtained representing the following HLA-A locus alleles: A^*01, A^*0102, A^*02, A^*0202, A^*0206, A^*0207, A^*03, A^*0302, A11.2, A11.1, A^*68, A^*68011, A^*30, A^*3002, A^*23, A^*24, A^*26, A^*2602, A^*25, A^*29, A^*2902, A^*31, A^*31011, A^*32, A^*3201, A^*33, A^*3301, A^*3303, A^*34, A^*6601, A^*6602 A^*74, A^*80. We found 21 polymorphic positions of which a surprisingly large number (altogether 9) represent allele specific exchanges. For all 35 alleles tested of the HLA-A locus we found 16 different types of promoter. While all tested A2 subtypes, A^*0201, A^*0202, A^*0206, A^*0207 share the same promoter, there were in contrast several situations in which different subtypes of the same group have different promoters. This is true for HLA A^*01, A^*0102; A^*03, A^*0302; A^*30, A^*3002; A^*6601, A^*6602; A^*32, A^*3201; A^*29, A^*2902. Looking at the binding sites for nuclear factors, we observe that TATA-box, CAT-box, Enhancer B, the interferon response sequence and the Enhancer A (except HLA-A30 has one base exchange) are conserved within the HLA-A locus. The interferon response sequence shows for all A-locus alleles a double base pair exchange (TT for AC). In comparison with the promoter polymorphism of the HLA-B locus (Yao et al., 1995) we find a surprising diversity of the promoters in the HLA-A locus. While for the B-locus promoters large groups of sometimes strongly different alleles share the same promoter, in the HLA-A locus there is a private promoter for almost each allele and sometimes even each subtype. This lead to the conclusion that the promoter polymorphisms of the HLA-A and the HLA-B locus have been subjected to different selection pressure in evolution.     

Down the rabbit hole: assessing the influence of schizotypy on the experience of the Barbie Doll Illusion

Introduction: “Body swapping” illusions have been used to explore factors contributing to the experience of “owning” an artificial body. Preliminary research indicated that those people diagnosed with schizophrenia experience more vivid illusions of this kind than do “normal” individuals.

Objectives: Here, we explored whether participants who rated themselves “high” on the cognitive-perceptual factor of the Schizotypal Personality Questionnaire (SPQ) experienced a more compelling sense of immersion in a variation of the body swapping illusion: The Barbie Doll Illusion. We also hypothesised that these individuals would experience a change in size perception when immersed in the illusion.

Method: Forty-four participants wore a pair of Head-Mounted Display goggles connected to a video-camera, and thus a doll’s body replaced their own body in their visual field. In two conditions, touch was either applied synchronously or asynchronously to the doll’s and each participant’s leg. After each condition, participants filled out a questionnaire relating to their experience in the illusion. When both conditions were completed, they filled out the SPQ.

Results: Our first hypothesis was confirmed, which suggested that people with higher cognitive-perceptual SPQ scores do indeed experience a more compelling Barbie Doll Illusion; however, our second hypothesis was not supported.

Conclusion: Our study demonstrated, for the first time, that proneness to the positive and interpersonal factors of schizotypy in a normal population is sufficient to produce a compelling sense of swapping bodies.     

Development of the retinal pathway to the pretectum of the cat

The development of retinal projections to the pretectal complex of prenatal and early postnatal cats has been examined using the anterograde transport of horseradish peroxidase and tritiated amino acids. As early as embryonic day 38, the entire dorsal pretectum is penetrated by retinal ganglion cell axons. At this stage the bilateral complement of retinal efferents appears to be dispersed uniformly within the pretectal anlage. A week later, on embryonic day 46, indistinct foci of peroxidase reaction product can be discerned within 2 of the primordial nuclei: the nucleus of the optic tract and the olivary nucleus. By embryonic day 56, five distinct bilateral fields of retinal fiber termination are apparent within the following regions:

(i) the nucleus of the optic tract;

(ii) the pretectal olivary nucleus;

(iii) the posterior pretectal nucleus;

(iv) the anterior pretectal nucleus; and

(v) the medial pretectal nucleus. Four days before birth, on embryonic day 61, crossed and uncrossed retinal arbors are partially segregated within the nucleus of the optic tract and the pretectal olivary nucleus.

The early postnatal retinal connection to the pretectum has an overall pattern virtually indistinguishable from that of the mature cat. The ontogeny of the retinal influx to the pretectum is similar to that of the retinocollicular projection.⁶¹ However, the development of retinal projections to the pretectum and superior colliculus appears to lag behind those to the dorsal lateral geniculate nucleus.⁴⁹ These differences may reflect temporal and spatial gradients in the maturation of three major classes of retinal ganglion cells.     

Anatomy of the portal branches and the hepatic veins in the caudate lobe of the liver

The objective of this study was to analyze the caudate portal branches and their relationships with the hepatic caudate veins and propose a new nomenclature for the caudate branches based on their territory of distribution. We realized the fine dissection of the veins of the caudate lobe in 40 human livers fixed and preserved in formalin. In 15/40 (37.5%) cases there was a single branch to the caudate lobe. In 25/40 (62.5%) cases there was more than one branch, with a posterior caudate branch in 20/40 (50%) cases, an anterior caudate branch in 15/40 (37.5%) cases, a left caudate branch in 14/40 (35%) cases, and a right caudate branch in 8/40 (20%) cases. The most frequent combination detected (11/40, 27.5% of cases) was that of the posterior and anterior branches. The venous drainage of the caudate lobe and its papillary process was provided by the superior caudate hepatic vein in 23/40 (57.5%) cases, by the middle caudate vein in 35/40 (87.5%) cases (which was the only vein in 12/35 cases), and by the inferior caudate vein in 16/40 (40%) cases. In 11/40 (12.5%) cases there were accessory caudate veins, which emptied into the left and intermediate hepatic veins. The portal branches and the hepatic veins related to the caudate process were studied. In conclusion, the new nomenclature analyzes more precisely the distribution of the caudate portal branches.     

Coupling between the ribs and the lung in dogs

In contrast to the conventional theory, the external and internal intercostal muscles show marked rostrocaudal gradients in their actions on the lung. We hypothesized that these gradients are the result of a non-uniform coupling between the ribs and the lung. Rib displacements ( X _r) and the changes in airway opening pressure ( P _a,o) were thus measured in anaesthetized, pancuronium-treated, supine dogs while loads were applied in the cranial direction to individual pairs of odd-numbered ribs and in the caudal direction to individual pairs of even-numbered ribs. During cranial loading, X _r induced by a given load increased gradually with increasing rib number. The decrease in P _a,o also increased from the third to the fifth rib pair but then decreased markedly to the eleventh pair. A similar pattern was observed during caudal loading, although X _r and Δ P _a,o were smaller. These results were then combined to calculate the net X _r and the net Δ P _a,o that a hypothetical intercostal muscle lying parallel to the longitudinal body axis would produce in different interspaces. The net X _r was cranial in all interspaces. However, whereas the net Δ P _a,o was negative in the cranial interspaces, it was positive in the caudal interspaces. These observations confirm that the coupling between the ribs and the lung varies from the top to the base of the ribcage. This coupling confers to both the external and the internal intercostal muscles an inspiratory action on the lung in the cranial interspaces and an expiratory action in the caudal interspaces.     

The influence of the nervous system on the composition of the blood

Summary Followed-up-after-discharge reactions were studied in the nervous system of laboratory animals in experimental anemia induced by phenylhydrazine. The method of the second blow with towing (Speranskii) was employed. It was possible to reproduce, to a certain degree, the blood picture characteristics of phenylhydrazine poisoning at the time when the blood picture almost reached its initial stage. It could particularly be reproduced in the line of the changes of processes of regeneration.The data which was thus obtained gave theoretical foundation to these phenomena, which are sometimes met in clinical practice as relepses of certain diseases of the blood system.Presented by Academician A. D. Speranskii     

Exercise hyperaemia in the heart: the search for the dilator mechanism

Coronary blood flow is tightly coupled to myocardial oxygen consumption to maintain a consistently high level of myocardial oxygen extraction over a wide range of physical acitivity. This tight coupling has been proposed to depend on periarteriolar oxygen tension, signals released from cardiomyocytes (adenosine acting on K_ATP channels) and the endothelium (prostanoids_, nitric oxide, endothelin) as well as neurohumoral influences (catecholamines, endothelin), but the contribution of each of these regulatory pathways, and their interactions, to exercise hyperaemia in the human heart are still incompletely understood. Thus, in the human heart, nitric oxide, prostanoids, adenosine and K_ATP channels each contribute to resting tone, but evidence for a critical contribution to exercise hyperaemia is lacking. In dogs K_ATP channel activation together with adenosine and nitric oxide contribute to exercise hyperaemia in a non-linear redundant fashion. In contrast, in swine nitric oxide, adenosine and K_ATP channels contribute to resting coronary resistance vessel tone control in a linear additive manner, but are not mandatory for exercise hyperaemia in the heart. Rather, exercise hyperaemia in swine appears to involve K_Ca channel opening that is mediated, at least in part, by exercise-induced β-adrenergic activation, possibly in conjunction with exercise-induced blunting of an endothelin-mediated vasoconstrictor influence. In view of these remarkable species differences in coronary vasomotor control during exercise, future studies are required to determine whether exercise hyperaemia in humans follows a canine or porcine control design.     

Effects of inflation on the coupling between the ribs and the lung in dogs

The coupling between the ribs and the lung in dogs increases with increasing rib number in the cranial part of the rib cage and then decreases markedly in the caudal part. The hypothesis was raised that this non-uniformity is primarily related to differences between the areas of the lung subtended by the different ribs, and in the current study we tested this idea by assessing the effects of passive lung inflation. Thus, by causing a descent of the diaphragm, inflation would expand the area of the lung subtended by the caudal ribs and improve the coupling between these ribs and the lung. The axial displacements of the ribs and the changes in airway opening pressure (Δ P _ao) were measured in anaesthetized, pancuronium-treated, supine dogs while loads were applied in the cranial direction to individual rib pairs at functional residual capacity (FRC) and after passive inflation to 10 and 20 cmH₂O transrespiratory pressure. In agreement with the hypothesis, inflation caused an increase in Δ P _ao for ribs 9 and 10. The most prominent alteration, however, was a marked decrease in Δ P _ao for ribs 2–8; at 20 cmH₂O, Δ P _ao for these ribs was only 30% of the value at FRC. Additional measurements indicated that this decrease in Δ P _ao results partly from the increase in diaphragmatic compliance but mostly from the reduction in outward rib displacement. This alteration in the pattern of rib motion should add to the decrease in muscle length to reduce the lung expanding action of the external intercostal muscles at high lung volumes.     

Nephritogenicity of the lprcg gene on the MRL background.

The novel lymphoproliferative and autoimmune lprcg gene, originally discovered in the CBA/K1Jms (CBA) strain of mice, was transferred onto the MRL/MpJ (MRL) strain background, and the resultant partially congenic MRL-lprcg/lprcg carrying 93% or more MRL genomes on average were examined for immune-complex glomerulonephritis and serological aberrations. Ordinary histological studies revealed that MRL-lprcg/lprcg mice developed glomerulonephritis histologically indistinguishable from that in MRL-lpr/lpr but at a lower frequency than in MRL-lpr/lpr mice. Glomerular immune complex deposition was almost the same in MRL-lprcg/lprcg and MRL-lpr/lpr mice. The levels of serum Ig, circulating immune complexes and autoantibodies in MRL-lprcg/lprcg were comparable to or even higher than those in MRL-lpr/lpr mice. Comparison of the serological abnormalities between MRL-lprcg/lprcg with glomerulonephritis and CBA-lprcg/lprcg without it evidenced the enhanced class switch from IgM to IgG responses in both class-specific autoantibody responses and serum Ig levels in MRL-lprcg/lprcg as in MRL-lpr/lpr mice. These results taken together indicate that the lprcg gene functions in much the same manner as lpr in induction of glomerulonephritis and serological abnormalities on the MRL background as expected from the allelism between the two mutant genes.     

Coherence analysis of the electrical activity of the rabbit brain in the process of the formation of the polarization dominant

It has been demonstrated by means of the method of spectral coherence analysis in rabbits, under conditions of a chronic experiment, that when a motor dominant reaction is still absent in the early stages of the dominant, interhemispheric asymmetry appears in the Coh spectra of the electrical activity of the sensorimotor cortex and the VPL nucleus of the thalamus. On the other hand, interhemispheric asymmetry appears in the Coh spectra of the electrical activity of the sensorimotor cortex and the CA ₃ field of the dorsal hippocampus only at the stage at which the motor dominant reaction is recorded. The asymmetry in the alpha and beta ranges of the frequencies in the Coh spectra of the biopotentials of the investigated regions, which coincides with the attainment of the motor dominant reaction, is associated with the processes of the organization of movement.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 39, No. 3, pp. 520–526, May–June, 1989.     

Effect of the host's body genotype and phenotype on the manifestation of the pathogenic properties of the influenza virus

The sensitivity of mice of CBA (H-2k haplotype), C57BL/6 (H-2b haplotype) strains and their hybrids M1 and F2 to the pathogenic influenza A/PR8/34 (H0N1) and nonpathogenic A/Krasnodar/101/59 (H2N2) virus strains was studied. The lethality, virus replication in the lungs, and the thymic index were determined. An increase in the resistance to the pathogenic influenza virus was found in male C57BL/6 and male F1 (CBA X C57BL/6) hybrids in the summer period as compared with winter. Replication of the pathogenic virus in the lungs of mice, in contrast to the nonpathogenic one, was accompanied by marked atrophy of the thymus. The study suggests the existence of a certain association between the resistance to influenza infection and phenotypic changes in the host connected with the weight of the thymus and the presence of mature T-lymphocytes.     

Phenotypic Characterization of Macrophages in the Endometrium of the Pregnant Cow

Problem  Macrophages are recruited in large number to the interplacentomal endometrium of the cow during pregnancy. We evaluated whether endometrial macrophages also accumulate in placentomal regions of endometrium during pregnancy and whether endometrial macrophages are regionally differentiated.
Method of study  Interplacentomal endometrium and placentomes were subjected to dual-color immunofluorescence using CD68 as a pan-macrophage marker.
Results  CD68⁺ cells were abundant in stroma of the interplacentomal endometrium and caruncular septa of the placentomes. CD68⁺ cells were not present in fetal villi of the placentomes or in the interplacentomal chorion. Regardless of location, the majority of CD68⁺ cells also expressed CD14. In interplacentomal endometrium, CD68⁺CD11b⁺ cells were present in deeper areas of the stroma but not in shallow endometrial stroma. In caruncular septa of the placentome, CD68⁺ cells were negative for CD11b. CD68⁺ cells in the interplacentomal endometrium were negative for MHC class II while most CD68⁺ cells in caruncular septa were positive for MHC class II.
Conclusion  CD68⁺CD14⁺ macrophages present in the stroma of the interplacentomal endometrium and caruncular septa of the placentome are regionally differentiated with regard to expression of CD11b and MHC class II.     

Anatomy of the intrahepatic ramification of the portal vein in the right hemiliver

The ramification of the portal vein in the right hemiliver was studied by anatomic dissection in 36 formalin-fixed human livers. In 28/36 (77.8%) cases, the portal vein bifurcated into a right branch and a left branch and the right branch bifurcated into anterior and posterior segmental branches. The anterior segmental branch terminated in the anterosuperior subsegment (S(8)) in two types: bifurcated when it divided into anterior P(8) and posterior P(8 )branches towards the respective regions of S(8) (24/28 cases) and monopodal when it had a single pedicle (4/28 cases). The maximum anteroinferior subsegmental branch (P(5 )maximum) originated either from the anterior segmental branch (16/28 cases) or from the anterior P(8) branch (12/28 cases). The posterior segmental branch vascularized the posteroinferior (S(6)) and the posterosuperior (S(7)) subsegments, and was terminated in three types: fan-shaped (16/28), bifurcated (9/28) and tripodal (3/28). In 4/36 (11.1%) cases the portal vein bifurcated into a right branch and a left branch but the posterior segmental branch was not present. In 4/36 (11.1%) the right branch of the portal vein was not present. These anatomical variations are explained separately and finally all cases are considered as a whole.     

On the Orientation of the HL-A Region and the PGM3 Locus in the Chromosome

A study of four families with a cross-over within the HL—A region and in which the crossover parent is heterozygous at PGM₃ indicates with a probability of about 95% that the chromosomal orientation of the three linked loci is LA · FOUR · PGM₃.     

Evolution of the NS genes of the influenza a viruses. II. Characteristics of the amino acid changes in the NS1 proteins of the influenza a viruses

We compared the amino acid sequences of the NS1 proteins of human, equine, and avian influenza viruses. The ratios of the amino acid substitutions per nucleotide substitutions in the NS1 proteins were about 27–45%, suggesting the existence of constraints on the amino acid changes of the NS1 protein in evolution. As a measure of constraints exerted on the regions of a protein, a changeability index is proposed. There was a highly conserved region between amino acid residues 30 and 50. The C-terminal region of amino acid residue 165 was a continuously changeable region. We have either introduced several nucleotide substitutions to the NS cDNA of the A/Udorn/72 virus in vitro or constructed the recombinant NS cDNAs between the A/Udorn/72 and A/chick/Japan/24 viruses, and then expressed them in animal cells. We have found that the amino acid substitutions introduced to the low-conserved region of the NS1 protein affected the stability and nuclear localization of the NS1 protein. One of the chimeric proteins between the A/Udorn/72 and A/chick/Japan/24 viruses did not move to the nucleus of the cell and remained in the cytoplasm.     

Gross morphology of the bridges over the vertebral artery groove on the atlas

The bony bridges of the atlas over the groove of the vertebral artery are commonly seen in plain radiographs of the cervical spine, and it is a subject of controversy whether they cause compression of the underneath lying vertebral artery. To clarify this we examined a total of 176 dried and complete atlas vertebrae and found the presence of a canal for the vertebral artery (CVA) in 10.23% and an incomplete canal for the vertebral artery in 24.43%. The CVA and incomplete CVA is more common in males (11.11% and 24.9%) than in females (9.3% and 24.42%). We found a higher incidence of CVA in laborers (37.5%) than in nonlaborers (4.16%). The incomplete CVA appeared to be more characteristic in the age group of 5–44 years. In the age group of 45–90 years the CVA was characteristic, which probably means that an incomplete CVA is the precursor of a CVA. The superoinferior diameter of the CVA canal ranged from 5.1 to 6.1 mm at the right side and from 4.6 to 5.8 mm at the left side, while the anteroposterior diameter was 5.6–6.9 mm at the right side and 6.1–7.2 mm at the left side. We also found a high incidence of coexistence of CVA and the retrotransverse foramen (72.22%) which means that because of possible compression of the vertebral veins the blood flow is directed into the small vein of the retrotransverse foramen. Finally, in 93.5% of unilateral CVA a deeply excavated contralateral groove of the vertebral artery was found.     

Pharmacological targeting of the serotonergic system for the treatment of obesity

The attenuation of food intake as induced by an increase in serotonergic (5-hydroxytryptamine, 5-HT) efficacy has been a target of antiobesity pharmacotherapies. However, the induction of tolerance and/or side-effects limited the clinical utility of the earliest serotonin-related medications. With the global prevalence of obesity rising, there has been renewed interest in the manipulation of the serotonergic system as a point of pharmacological intervention. The serotonin_2C receptor (5-HT_2CR), serotonin_1B (rodent)/serotonin_1Dβ (human) receptor (5-HT_1B/1DβR) and serotonin₆ receptor (5-HT₆R) represent the most promising serotonin receptor therapeutic targets. Canonical serotonin receptor compounds have given way to a myriad of novel receptor-selective ligands, many of which have observable anorectic effects. Here we review serotonergic compounds reducing ingestive behaviour and discuss their clinical potential for the treatment of obesity.     

The sonographic and endocrinologic evaluation of the endometrium in the luteal phase

Follicular development and the endometrial thickness were determinedsonographically in 19 outpatients with different causes of sterility,treated during natural or stimulated cycles. The estimates ofthe endometrial thickness, assessed by ultrasound in the mid-lutealphase, and the levels of 17-oestradiol and progesterone in thesame patients sampled on the day of sonography were compared.Five patients became pregnant (group 1) and showed good progesteronevalues. Eight patients who were not pregnant showed progesteronevalues above 15 ng/ml in the mid-luteal phase (group 2). Theprogesterone values of group 3 were below 15 ng/ml by definition.The mean endometrial thickness in group 1 (= 11.3 mm) and group 2 ( = 11.8 mm) weresignificantly higher than that of group 3 (= 8.3 mm). The sonographic measurement of the mid-luteal endometriumthickness serves as an additional criterion for the evaluationof the secretory phase of the menstrual cycle.     

Exploring the use of the Hinting Task in first-episode psychosis

Introduction: The aim of the study was to elucidate the association between performance-related neurocognitive abilities and Theory of Mind (ToM) as measured by the Hinting Task (HT) performance and investigate the psychometric properties of the HT for use in First-Episode Psychosis (FEP).

Methods: Cross-sectional data of 132 participants with FEP, aged 15–25 years, enrolled in a randomised controlled trial of vocational intervention, were analysed. A comprehensive cognitive battery including social cognitive and neurocognitive measures, a social and occupational functioning measure and psychopathological measures, were used. Psychometric properties were measured through bivariate correlations and associations with neurocognitive domains were assessed through hierarchical regression.

Results: Low convergent validity of the HT with other ToM measures, moderate discriminant validity with an emotion recognition task, low predictive validity with social and occupational functioning, and high internal consistency were revealed. HT performance was significantly associated with verbal reasoning and verbal memory.

Conclusion: Results provide preliminary evidence of low convergent validity and moderate discriminant validity of the HT in FEP, and the influence of verbal reasoning and verbal memory on HT performance, indicating that caution is warranted when employing the HT as a screening tool in isolation for detection of ToM deficits in FEP.