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Biomedical subjects

E Gunther

Publications and source records attributed to E Gunther.

14 recordsLinked to original sources

Hormone-dependent tumor regression in vivo by an inducible transcriptional repressor directed at the PAX3-FKHR oncogene.

In alveolar rhabdomyosarcomas (ARMSs), a specific chromosomal translocation creates a fusion transcription factor, PAX3-FKHR, that is oncogenic due to transcriptional activation. As a strategy for down-regulation of PAX3-FKHR target genes, we created conditional PAX3 repressors by fusing the PAX3 DNA-binding motifs to the hormone binding domain (HBD) of the estrogen receptor and to the KRAB repression domain. We validated proper expression, specific DNA binding, corepressor interaction, and nuclear localization for the KRAB-PAX3-HBD protein and showed it to be a 4-hydroxytamoxifen-dependent transcriptional repressor of transiently transfected and integrated PAX3 reporters in ARMS cells. We established ARMS cell lines that exhibited stable expression of the conditional PAX3 repressor proteins and used them to down-regulate the malignant growth under low serum or anchorage-independent conditions in a hormone-dependent manner. Terminal deoxynucleotidyl transferase-mediated nick end labeling assays revealed that hormonal activation of the PAX3 repressors induced extensive apoptosis that correlated with down-regulation of BCL-X(L) expression. SCID mice that were engrafted with the KRAB-PAX3-HBD ARMS cell lines and were implanted with 4-hydroxytamoxifen timed-release pellets exhibited suppression of tumor growth and an altered vascularity that was not observed in the control mice. These observations strongly suggest that we have directly repressed the PAX3 target genes that are deregulated by the PAX3-FKHR oncogene in ARMS.

3T3 Cells↗

Tongue-base suspension with a soft tissue-to-bone anchor for obstructive sleep apnea: preliminary clinical results of a new minimally invasive technique.

The Repose system is a new minimally invasive technique for tongue-base suspension in the treatment of sleep-disordered breathing caused by tongue-base collapse. It involves the insertion of a titanium miniscrew with attached suture into the anterior intraoral mandible and passing the suture through the tongue base. The procedure was performed in 16 patients with sleep-disordered breathing. Fourteen patients reported an improvement in daytime sleepiness, and their bed partners reported an improvement in snoring. The mean respiratory distress index before surgery was 35. Two months after surgery, the mean respiratory distress index was 17, an improvement of 51.4% (P = 0.001, 2-tailed t test). These preliminary results show the initial efficacy and safety of this new surgical procedure.

Adult↗

Standardization of 237Np by the CIEMAT/NIST LSC tracer method

The standardization of 237Np presents some difficulties: several groups of alpha, beta and gamma radiation, chemical problems with the daughter nuclide 233Pa, an incomplete radioactive equilibrium after sample preparation, high conversion of some gamma transitions. To solve the chemical problems, a sample composition involving the Ultima Gold AB scintillator and a high concentration of HCl is used. Standardization by the CIEMAT/NIST method and by pulse shape discrimination is described. The results agree within 0.1% with those obtained by two other methods.

Journal Article↗

Palatoplasty: Furlow's double reversing Z-plasty versus intravelar veloplasty.

OBJECTIVE: To evaluate the efficacy of Furlow's double reversing z-plasty (Furlow) versus intravelar veloplasty with longitudinal closure including palatal muscle reorientation (IVV). DESIGN: Retrospective, single-institution, single-surgeon comparison. PATIENTS: One hundred nineteen consecutive cleft palate patients were enrolled; 34 syndromic and 9 language-impaired patients were removed from speech and reoperation analysis. Furlow and IVV groups were similar with respect to sex and mean age at primary repair. INTERVENTIONS: One surgeon performed all surgery and one of two speech pathologists conducted language and speech evaluations at 3 years of age without prior knowledge of the surgical technique utilized. OUTCOME MEASURES: Outcome measures included frequency of palatal fistulae, speech abnormalities, and need for secondary pharyngoplasty procedures. RESULTS: Patients who had undergone IVV demonstrated a 34% higher incidence of hoarseness, nasal escape, and hypernasality at 3 years of age than did Furlow patients. These same patients likewise required significantly more secondary pharyngoplasty procedures. No significant difference was noted between fistulae frequencies. CONCLUSIONS: These findings suggest that Furlow palatoplasty may provide a better clinical outcome than intravelar veloplasty.

Cleft Palate↗

Purification and some properties of streptococcal NAD-glycohydrolase.

NAD-glycohydrolase (NADase) was purified from culture supernatant fluids of group C streptococci by adsorption on silica gel, chromatography on hydroxyapatite and ion exchange on Mono S column. After inactivation of a chymotrypsin-like protease, a homogeneous enzyme was isolated with an N-terminal sequence of VSGKEGKKSDVKYEMTKVMEANATSSKEDKHVMHTLDKVM. According to serological methods, the purified enzyme of group C streptococci was identical to the group A enzyme showing a specific activity of 10 000 000 U mg-1. It did not attack NADH, NADP or NADPH. In addition, a streptodornase was isolated having an N-terminal sequence of KTVSVNQTYGE.

Amino Acid Sequence↗

Kinetics and regulation of erythrogenic toxins type A and C during growth of Streptococcus pyogenes.

The production of erythrogenic toxins type A (ETA) and C (ETC) is described as a function of growth kinetics. Group A streptococcal strains C 203 S and NY 5 were cultivated in yeast-peptone extract, Todd-Hewitt medium and a synthetic medium. Two main growth phases occurred during growth: a first logarithmic phase and a second linear phase. These phases were separated by a short stationary interphase caused by limitation of the amino acids L-serine and L-leucine. Maximum production of ETC was observed during the logarithmic phase, it was correlated to a high level of viable cells. ETA was produced mainly during the short stationary interphase. The production of ETC is regulated by L-isoleucine. A stagnation or reduction of the concentration of viable cells was observed during the interphase. The phosphate limitation caused during streptococcal growth induced expression of the extracellular protein phosphatase and surprisingly, of a serine proteinase activity. The association between these results and the pathogenicity of streptococci is discussed.

Acid Phosphatase↗

Changes in bone in a model of spinal cord injury.

Bone calcium, histomorphometry, and mechanical strength were evaluated in a model of spinal cord injury. Cortical bone area and rates of formation and apposition at the tibiofibular junction (TFJ) and midshaft of the humerus were measured at 35-42, 42-77, and 77-94 days after transection of the spinal cord. All comparisons were between the animals with a spinal lesion and control animals. A 0.34% difference in the length of the tibia of the two groups of animals was observed, the dry weight of the tibia was 28.4% less in rats with a lesion, and there was no significant difference in the amount of calcium per milligram of bone. At 35 days after surgery, the cortical area in the midshaft of the humerus was slightly less (11%) in rats with a lesion, but by 94 days there was no difference in cortical or medullary area. The final (day 94) cortical area at the TFJ in rats with a lesion was less than that in the controls. Bone formation at the TFJ was similar in both groups in the period of 35-42 days and was similar at 77-94 days in the animals with a lesion, and rates of formation and apposition were greater in the humerus of rats with a lesion; the rates did not differ significantly between groups at either site. At 94 days, trabecular bone area in the tibial metaphysis was 41% less in rats with a lesion. Mechanical parameters were significantly less in the femora, but not the humeri, of rats with a lesion.

Animals↗

Colonization of pregnant women and their newborn infants with group B streptococci in the Gondar College of Medical Sciences.

In a study of Group B streptococcal carriage, 200 postpartum women and 80 newborn infants were investigated in the Gondar College of Medical Sciences from January to April 1987, using swabs from the vagina and rectum, and from the throat and external ear, respectively. We found a colonization rate of 9% (18/200) in the mothers and 5% (4/80) in the neonates. The serological typing of the 25 isolated strains showed 60% (15/25) to be Type Ib/c and 16% (4/25) to be Type Ia strains. Therefore, in newborn infants with infections, diagnostic and bacteriological procedures should include a search for Group B Streptococci.

Carrier State↗

Immune complex type disease induced by HgCl2 in Brown-Norway rats: genetic control of susceptibility.

Mercuric chloride induces a biphasic autoimmune glomerulonephritis in Brown-Norway (BN) rats but not in Lewis (LEW) rats. The genetic control of susceptibility to both phases was investigated by testing the response of segregants between BN and LEW rats and of congenic LEW.1N rats. It was confirmed that susceptibility to the first phase, characterized by the appearance of anti-glomerular basement membrane antibodies, depends on several genes one of which is RT1 linked. Susceptibility to the second phase, which is an immune complex type glomerulonephritis, was found to depend on one major RT1 linked gene or cluster of genes with a role for other(s) non-RT1 linked gene(s) controlling the magnitude of the response. However, congenic LEW.1N rats were found to be resistant. This suggests that the disease gene has been lost during the strain derivation. The question of whether both phases are two different diseases or expression of the same process cannot be definitely answered; data however indicate a dissociation of both disease processes.

Animals↗

Non-major histocompatibility system immunogenetic influences in rat renal allograft survival.

H-1-incompatible rat renal allograft survival rates are strongly influenced by the non-major histocompatibility system (MHS) genes. The same H-1 (MHS) incompatibility tested on four different non-MHS backgrounds gave widely differing results ranging from 11 to 60% fractional survival between the best and the poorest (P less than 0.01) at 105 days. These results can best be explained if non-H-1 and intra-MHS amplifiers and/or suppressors are invoked.

Animals↗

Stimulation and suppression of rat mast cell functions by alloantibodies.

The stimulatory as well as the inhibitory capacity of alloantisera has been investigated with respect to rat mast cell functions. Alloantibody against alloantigens coded for by the major histocompatibility (H-1) gene region promoted histamine release from purified LEW mast cells. This process was found to be complement-independent but demonstrated an absolute requirement for calcium. Pretreatment of mast cells with anti-H-1 antisera in the absence of calcium markedly suppressed the IgE-dependent histamine release challenged either by antigen or by anti-IgE antibody. The alloantisera, however, did not interfere with the ability of compound 48/80-associated histamine liberation. Additionally, antibodies specific for H-1 antigens were highly effective in inhibiting the binding of IgE to the mast cell surface. Alloantisera absorbed with erythrocytes lost their capacity to block mast cell functions. Based on these data the possible ralationship between H-1 alloantigens and the IgE receptor on the mast cell surface is discussed.

Animals↗

Ionization quenching in LSC.

Ionization quench function Q(E) introduces an important correction in the CIEMAT/NIST tracing method. In this paper we present a detailed analysis of the equations used to compute the counting efficiency of 55Fe. The counting efficiency of this radionuclide is very sensitive to the shape and values of Q(E) for this method. We demonstrate that the Birks equation and stopping power are not adequate to obtain low discrepancies between the experimental and computed efficiencies. An empirical procedure to compute accurate Q(E) functions is also given.

Algorithms↗