HLA-DRB1 and -DQB1 alleles in the Brazilian population of the northeastern region of the state of São Paulo

The HLA-DRB1 and -DQB1 alleles in 161 healthy unrelated individuals, including Caucasians, Blacks and Mulattos (mixed Caucasian and Black), from the Northeastern region of the state of S?o Paulo, Brazil were analysed. The 36 different DRB1 alleles detected included not only common Caucasian alleles, but also DRB1*0411, 0807 and 1402, typical of Amerindians, and DRB1*0302, 1503, and 0804, typical of African American Blacks.     

Mapping of the functional domains of the α 4 protein of herpes simplex virus 1

Summary Truncated 4 genes were introduced into BHK tk^– cells along with the neomycin phosphotransferase gene, that confers resistance to the eukaryotic antibiotic G 418, driven by the HSV-1 tk promoter ( tk^–neo^r). Stably transformed cell lines were obtained and studied for the ability of the resident truncated 4 genes to regulate the expression of the tk^–neo^r, and for the ability of the truncated 4 polypeptides to localize to the nuclei of transformed cells. The results indicated that the domain(s) for gene induction and for nuclear localization of the 4 protein are located within the N-terminal 288 amino acids of the protein.     

Importance of the mutation of amino acid 200 of the isotype 1 β-tubulin gene in the benzimidazole resistance of the small-ruminant parasite Teladorsagia circumcincta

In this work we demonstrated that the acquisition of benzimidazole (BZ) resistance in the small- ruminant parasite Teladorsagia circumcincta is linked to the selection of individuals that are characterized by a tyrosine (Tyr) at amino acid 200 of their isotype 1 β-tubulin gene. This mutation appears to be recessive, since only homozygous mutant (Tyr/Tyr) individuals survived after BZ treatment of two resistant populations in which the three genotypes (rr, rs, ss) were initially present. In comparison with natural BZ-susceptible populations, a decrease in the restriction polymorphism (RFLP) of the isotype 1 β-tubulin gene was observed in natural resistant populations. It seems that this decrease in β-tubulin polymorphism results from the selection of homozygous mutant individuals. Received: 5 October 1998 / Accepted: 16 December 1998     

Cross-sectional study of the ossification center of the C1–S5 vertebral bodies

Purpose

Knowledge on the normative growth of the spine is relevant in the prenatal detection of its abnormalities. This study describes the size of the ossification center of C1–S5 vertebral bodies.

Materials and methods

Using CT, digital-image analysis, and statistics, the size of the ossification center of C1–S5 vertebral bodies in 55 spontaneously aborted human fetuses aged 17–30 weeks was examined.

Results

No sex significant differences were found. The body ossification centers were found within the entire presacral spine and in 85.5 % of S1, in 76.4 % of S2, in 67.3 % of S3, in 40.0 % of S4, and in 14.5 % of S5. All the values for the atlas were sharply smaller than for the axis. The mean transverse diameter of the body ossification center gradually increased from the axis to T12 vertebra, so as to stabilize through L1–L3 vertebrae, and finally was intensively decreasing to S5 vertebra. There was a gradual increase in sagittal diameter of the body ossification center from the axis to T5 vertebra and its stabilization for T6–T9 vertebrae. Afterward, an alternate progression was observed: a decrease in values for T10–T12 vertebrae, an increase in values for L1–L2 vertebrae, and finally a decrease in values for L3–S5 vertebrae. The values of cross-sectional area of ossification centers were gradually increasing from the axis to L2 vertebra and then started decreasing to S5 vertebra. The following cross-sectional areas were approximately equivalent to each other: for L5 and T3–T5, and for S4 and C1. The volumetric growth of the body ossification center gradually increased from the axis to L3 vertebra and then sharply decreased from L4 to S5.

Conclusions

No male–female differences are found in the size of the body ossification centers of the spine. The growth dynamics for morphometric parameters of the body ossification centers of the spine follow similarly with gestational age.     

Effect of Interleukin-1β on the Expression of Tight Junction Proteins in the Culture of HaCaT Keratinocytes

We studied the effect of IL-1β on the expression of tight junction proteins (occludin and claudins) in cultured HaCaT keratinocytes and changes of transepithelial resistance. Addition of IL-1β had little effect on transepithelial resistance, increased the expression of claudin-1, and did not modify the expression of occludin. In other tissues, IL-1β also increases claudin-1 expression, but significantly decreases occludin expression. These changes are accompanied by the reduction of transepithelial resistance. The IL-1β-induced increase in the expression of claudin-1 in cultured HaCaT keratinocytes simulates the appearance of claudin-1 at the early stage of skin wound healing. It is accompanied by an increase in IL-1β concentration in the wound fluid.     

BRMS1 contributes to the negative regulation of uPA gene expression through recruitment of HDAC1 to the NF-κB binding site of the uPA promoter

The BRMS1 metastasis suppressor was recently shown to negatively regulate NF-κB signaling and down regulate NF-κB-dependent uPA expression. Here we confirm that BRMS1 expression correlates with reduced NF-κB DNA binding activity in independently derived human melanoma C8161.9 cells stably expressing BRMS1. We show that knockdown of BRMS1 expression in these cells using small interfering RNA (siRNA) leads to the reactivation of NF-κB DNA binding activity and re-expression of uPA. Further, we confirm that BRMS1 expression does not alter IKKβ kinase activity suggesting that BRMS1-dependent uPA regulation does not occur through inhibition of the classical upstream activators of NF-κB. BRMS1 has been implicated as a corepressor of HDAC1 and consistent with this, we show that BRMS1 promotes HDAC1 recruitment to the NF-κB binding site of the uPA promoter and is associated with reduced H3 acetylation. We also confirm that BRMS1 expression stimulates disassociation of p65 from the NF-κB binding site of the uPA promoter consistent with its reduced DNA binding activity. These data suggest that BRMS1 recruits HDAC1 to the NF-κB binding site of the uPA promoter, modulates histone acetylation of p65 on the uPA promoter, leading to reduced NF-κB binding activity on its consensus sequence, and reduced transactivation of uPA expression.     

Loss of β1-integrin-deficient cells during the development of endoderm-derived epithelia

β1-Integrins (β1) represent cell surface receptors which mediate cell–matrix and cell–cell interactions. Fässler and Meyer described chimeric mice containing transgenic cells that express the LacZ gene instead of the β1 gene. They observed β1-negative cells in all germ layers at embryonic day E 8.5. Later in development, using a glucose phosphate isomerase assay of homogenized tissue samples, high levels of transgenic cells were found in skeletal muscle and gut, low levels in lung, heart, and kidney and none in the liver and spleen (Fässler and Meyer 1995). In order to study which cell types require β1 during development of the primitive gut including its derivatives, chimeric fetuses containing 15 to 25% transgenic cells were obtained at days E 14.5 and E 15.5. They were LacZ (β-galactosidase) stained “en bloc” and cross-sectioned head to tail. In esophagus, trachea, lung, stomach, hindgut, and the future urinary bladder, we observed various mesoderm-derived β1-negative cells (e.g. fibroblasts, chondrocytes, endothelial cells, and smooth muscle cells) but no β1-negative epithelial cells. Since the epithelia of lung, esophagus, trachea, stomach, hindgut, and urinary bladder are derived from the endodermal gut tube, we hypothesize that β1 is essential for the development and/or survival of the epithelia of the fore- and hindgut and its derivatives.     

The performance of the VIKIA(®) HIV1/2 rapid test-evaluation of the reliability and sensitivity

The use of rapid human immunodeficiency virus (HIV) antibody tests can help reduce the number of individuals positive for HIV who are unaware of their infection.Although several studies have demonstrated that the sensitivity and specificity of rapid HIV tests are comparable to those of enzyme immunoassays, none have addressed the rapidity with which these tests can yield a result and the reliability of such results. In this study, we investigated the performance of VIKIA^® HIV1/2 rapid tests regarding early reactive results and the stability of these results after sample addition. The results showed that using HIV-1 or HIV-2 positive samples, a positive result could be observed as early as 1 min after the addition of the sample. The ability of this test to detect early HIV-1 primary infection was also assessed using seroconversion specimens. The results demonstrate the high sensitivity of this test, and its suitability for the identification of seroconversion samples in the context of primary infection with HIV-1.     

Place of genotyping in addition to the phenotype and the assay of serum α-1 antitrypsin

The diagnosis of deficiency of alpha-1 antitrypsin (A1AT) is based on isoelectric focusing of serum proteins and the extent of serum. However, the focusing is technically difficult and a greatly reduced concentration in abnormal A1AT tapeless does not differentiate an unstable variant of a variant called 'null' (that is to say without any phenotypic expression) to 'heterozygous' state. In this study, we compared the results of the assay, the phenotype and genotype of A1AT in 50 patients. Normal A1AT alleles (Pi*M1 to Pi*M4) or loss of the most common (Pi*S and Pi*Z) were clearly identified in phenotyping. However, genotyping was necessary to characterize: (i) certain alleles rarer A1AT (S-Munich, X-Christchurch); (ii) a null allele and; (iii) two new alleles A1AT not yet described in the literature. In conclusion, although the A1AT genotyping is generally not necessary, it is necessary to resolve complex cases and to obtain witnesses validated for isoelectric focusing.     

Reflex regulation of the “spontaneous” activity of the chemoreceptors of the tongue

Summary The spontaneous activity of the chemoreceptors of the frog's tongue was studied during stimulation of the interoceptors of the stomach and of the sympathetic chain. It was found to be under the control of the nervous system, adapting the receptors to give improved perception, and it indicates the preparedness of these apparatuses to receive stimuli. Spontaneous activity may be fundamentally a partial principle of the functioning of receptor elements. Further electrophysiological investigations of this problem are proceeding.(Presented by Active Member AMN SSSR P. K. Anokhin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 55, No. 8, pp. 7–11, August, 1963     

Fibronectin regulates the activation of THP-1 cells by TGF-β1

OBJECTIVE AND DESIGN: To determine how fibronectin regulates the immunomodulatory effects of transforming growth factor (TGF)-beta on THP-1 cells. MATERIAL OR SUBJECTS: THP-1 monocytic cell line. TREATMENT: THP-1 cells were primed for 48 h in the presence or absence of 250 pM TGF-beta1. METHODS: Assays or assessments carried out, together with statistical test applied. RESULTS: We found that adherence to fibronectin dramatically modulates the effects of TGF-beta1 on the human monocytic cell line THP-1. TGF-beta did not significantly affect constitutive interleukin (IL)-8 secretion or IL-1beta-induced IL-8 secretion from suspended cells. In contrast, TGF-beta stimulated IL-8 secretion as well as augmented IL-1beta-induced IL-8 secretion from adherent cells. The differential effects of TGF-beta1 on IL-8 secretion from suspended and adherent cells could not be explained by differences in IL-1 receptor antagonist production. The effects of fibronectin on TGF-beta1 induced IL-8 secretion from THP-1 cells were mimicked by adhesion to immobilized anti-a4beta1 integrin antibody and to a fibronectin fragment containing the CS-1 domain. CONCLUSIONS: These results indicate that alpha4beta1-mediated adhesion to fibronectin may play a key role during inflammation by profoundly influencing the effects of TGF-beta1 on monocytes.     

Do hyporesponsive genetic variants of the melanocortin 1 receptor contribute to the etiology of multiple sclerosis?

Hyporesponsive genetic variants of the melanocortin 1 receptor result in pigmentary phenotypes exhibiting light skin and light color hair, including red hair. These variants are common in populations with high rates of multiple sclerosis, while rare in populations with low rates. Alpha-melanocyte stimulating hormone, the major ligand for this receptor, is responsible for phenotype determination, but is also known for its anti-inflammatory and immune modulating effects, including inhibition of factors implicated in multiple sclerosis pathology. As the melanocortin 1 receptor is expressed on various cell types involved in immune response, it is possible that carriers of hyporesponsive variants of this receptor lack the full anti-inflammatory and immune modulating effects of alpha-melanocyte stimulating hormone. It is proposed that these variants are part of a spectrum of genes involved in the etiology of multiple sclerosis. Related aspects of multiple sclerosis epidemiology are examined.     

Effect of Interleukin-1β on the Behavior of Rats during Mild Stress in the Open-Field Test

We studied the effect of interleukin-1β on the behavior of rats with different individual typological characteristics during mild stress in the open-field test. Intraperitoneal injection of interleukin-1β (5 μg/kg, 108 U/mg) was followed by a decrease in orientation and exploratory activity of passive and, particularly, of active animals in the open field. As differentiated from rats receiving physiological saline, the initial differences in behavioral characteristics of active and passive animals were not revealed in the repeated test after injection of interleukin-1β. We conclude that interleukin-1β abolishes the behavioral differences between active and passive specimens in the open field. These data suggest that administration of interleukin-1β to rats leads to reorganization of the mechanisms for emotional evaluation of adverse emotiogenic factors under conditions of mild stress in the open-field test.