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Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 469 records · Page 26Linked to original sources

fosB is a transforming gene encoding a transcriptional activator.

The fosB gene encodes a nuclear protein that shows a high degree of homology with c-Fos in several of the known functionally crucial domains, e.g., the leucine zipper and the DNA-binding site, but shows considerable divergence in other regions. Here, we report that FosB, when placed under the control of a constitutive promoter, exhibits clear transforming properties in focus assays using mouse NIH3T3 or rat 208F fibroblasts. The transforming potential of FosB is considerably stronger than that of a corresponding c-fos construct and resembles that of viral fos genes. Using chimeric fos/fosB constructs we show that the C-terminal half of FosB is responsible for these stronger transforming properties, apparently by giving rise to significantly higher levels of protein as compared with the corresponding c-fos sequence. Surprisingly, substitution of the N-terminus of Fos with that of FosB decreases its transforming potential. These differences in the transforming potential are not related to DNA or protein expression, but rather seem to reflect differences in the molecular function(s) encoded in the N-terminal halves of Fos and FosB protein. Both, fosB- and v-fos transformed cells show increased expression of a number of endogenous genes, including c-jun, transin, alpha 1(III) collagen and tissue plasminogen activator. Transactivation by FosB and v-fos of the c-jun and alpha 1(III) collagen gene promoters and of a 3 x TRE-tk chimeric promoter could be shown in transient CAT assays. v-Fos, but not FosB-transformed cells, also show elevated levels of urokinase and plasminogen activator inhibitor mRNAs, pointing to potential differences in the gene regulatory properties of the two Fos family members.

Animals↗

Mutagenesis of the DNA contact site in Fos protein: compatibility with the scissors grip model and requirement for transformation.

To elucidate the mechanisms involved in the transformation by fos we have initiated a study pertaining to the identification of molecular functions of Fos protein that are crucial for transformation. We have previously reported that the presence of an intact leucine zipper in Fos is an absolute requirement for the induction of transformation, but that the autorepression function of Fos is dispensable. We now show that Fos protein also needs an intact DNA (TRE)-binding site to be able to transform. Amino acid substitutions in this domain of Fos which impair DNA binding also destroy the transforming potential of Fos, suggesting that the interaction of Fos-Jun complexes with TREs may be a crucial part of Fos-induced transformation. This hypothesis is further strengthened by our observation that Fos and Jun can cooperate in the induction of transformation. We show that a Fos protein which contains a Jun leucine zipper and is thus capable of dimerization is still dependent on the presence of exogenous Jun to induce transformation. The critical positions in the Fos DNA-binding site include those which the 'scissors grip' model predicts to be crucial, although the DNA-binding site in Fos seems to extend beyond the basic region into an adjacent cluster of acidic amino acids.

Amino Acid Sequence↗

[An avoidable cause of parental anxiety and unnecessary medical workup: diaper crystals (pannolithiasis)].

Five infants aged 6 to 23 months had a history of passing crystals in urine. They were not ill, but micturition was reported to be associated with pain in two of them. Physical examination was normal, and urinalysis and culture were negative. In one case we observed "jelly-like crystals" of about 2 mm diameter which dissolved spontaneously in tap water. When the parents were re-questioned it became evident that all used a new brand of highly absorbent diapers. "Jelly-like crystals" developed in our laboratory when the absorbent material of the new diapers was put in contact with urine or tap water. The new highly absorbent diapers help to keep the baby dry. However, "jelly-like crystals" may be observed and possibly alarm both parents and physicians. Information for parents and physicians may avoid unnecessary anxiety or medical workup.

Crystallization↗

Procedure for the purification of streptavidin by hydrophobic interaction chromatography.

A procedure is described for the purification of hydrophobic microbial proteins such as streptavidin from Streptomyces avidinii, using Benzyl-DC bead cellulose as the column material. The separation is rapid with a high loading capacity and sufficient resolution for preparative uses. Advantages are discussed especially for industrial purposes.

Bacterial Proteins↗

Behavioral characteristics and laboratory parameters in homo- and bisexual men in West Berlin: an evaluation of five years of testing and counselling on AIDS.

Sera of 1980 homo- and bisexual men who visited the Landesinstitut für Tropenmedizin Berlin (West) between April 1983 and December 1987 were tested for HIV antibodies; 24.3% were positive. Of HIV-antibody-positive men, 78.9% reported both active and passive anal intercourse, 58.8%, rectal enemas, and 53.3%, use of butyl nitrite. There was a sexual partner with known positive HIV-antibody status or AIDS in 33.9%, and in 32.4% there was a history of sexual activity in the USA. In the year before the test, 18.8% had had more than 50 partners. All these behavioral characteristics were found to be significantly correlated to HIV antibodies. We noted a substantial reduction of high-risk behavior from 1983 to 1987. The most important behavioral factor for HIV infection in 1983 and 1984 was sexual activity in the USA, and from 1984 to 1987, the numbers of lifetime partners. Persons infected with HIV were significantly more often carriers of antibodies against HAV, HBV, CMV, EBV, and syphilis. Prevalence of antibodies against HIV, HAV, HBV, and syphilis increased with age, duration of homosexual practice, and the number of partners. Overall crude prevalence rates of HIV antibodies, anti-HBc, anti-HAV, and antibodies to syphilis declined during the observation period. Clinical findings such as fever, oral lesions, and lymphadenopathy syndrome (LAS) were found to be highly indicative of HIV infection. Lower hemoglobin values, a reduced white cell count, and hyperimmunoglobulinemia were significantly more frequent in subjects with HIV antibodies.

Adolescent↗

[Simple coagulation prophylaxis using low-molecular heparin enoxaparin in pediatric hemodialysis].

The use of low molecular weight heparins for the prevention of clotting in extracorporeal circulation during hemodialysis has been reported in adults. In seven children (aged 7 to 18 years) with end stage renal failure an initial bolus of the low molecular weight heparin enoxaparin (dosage: 24 to 36 mg/m2) provided simple and proper anticoagulation with no hemorrhage during at least four hours. The tolerance was excellent.

Adolescent↗

[Effects of nicotine on left ventricular diastolic function in patients with coronary disease. An echocardiographic study].

Echocardiography was performed before and after inhalation of 0.9 mg nicotine in 21 patients (6 women and 15 men with a mean age of 51.8 [38-73] years). All of them had angiographically confirmed coronary heart disease (stenosis greater than 50%) and smoked 20-50 cigarettes daily for at least 5 years. In addition, left ventricular filling parameters were determined by transmitral pulsed Doppler ultrasonography. In this technique the flow profile across the mitral valve is divided into the passive, early diastolic inflow (E wave) phase and the active, late diastolic inflow phase caused by atrial contraction (A wave). Isovolumetric relaxation time was measured by simultaneous M-mode recordings over the aortic and mitral valves. The following significant changes were noted after the dose of nicotine (medians; one-sided Wilcoxon test; P less than 0.05): peak velocity of the E wave decreased from 43 to 34.4 cm/s; the ratio between A and E wave peak velocities increased from 1.02 to 1.37; the velocity/time integral of the E wave decreased from 4.77 to 3.57 cm; the ratio between the velocity/time integrals of the A and E waves rose from 0.66 to 1.15; isovolumetric relaxation time increased from 90 to 121 ms. - In cigarette smokers with coronary heart disease, acute administration of nicotine hence caused a decrease in early diastolic transmitral blood flow and an increase in isovolumetric relaxation time. These changes point to significant impairment of left ventricular diastolic function.

Adult↗

HIV infection in intravenous drug abusers in Berlin: risk factors and time trends.

To investigate the epidemiology of HIV infection among intravenous drug abusers (IVDA) in Berlin (West), from October 1984 to October 1988, 741 heterosexual IVDA were recruited from facilities for drug treatment and counseling. In this group 22.8% were seropositive for antibodies against HIV, representing 21.1% of the females and 23.5% of the males. Seroprevalences of hepatitis B, hepatitis A, and lues were 67.7%, 40.1%, and 4.0%, respectively. Seropositivity for HIV antibodies correlated with positive seromarkers for hepatitis B and A, and with certain behavioral and social features such as sharing of injection equipment, imprisonment, and intravenous drug use in prison. The crude time trend of HIV seroprevalence shows an increase from 17.1% in those subjects who discontinued i.v. drug abuse in 1983 or earlier to 31.5% in 1985, and a decrease over the past 3 years to 14.1% in 1988. After adjusting for temporary changes in the study group, the estimated HIV seroprevalence odds show an almost steady increase and were significantly higher for those who were injecting drugs in 1987 and 1988 compared with those who stopped i.v. drug use before 1984. Thus IVDA with a persistent risk profile are at a still-increasing risk of acquiring HIV infection.

Age Factors↗

[Treatment of chronic hepatitis B with interferon alpha-2b].

In a prospective randomized trial 58 patients (46 men, 12 women; mean age 41 [18-65] years) with histologically proven chronic hepatitis B and demonstration of HBs antigen and hepatitis B virus DNA in serum were randomly divided into two groups: 30 patients were treated with recombinant alpha 2b interferon. The interferon was administered subcutaneously, 3 x 10(6) IU, three times weekly for four months. 28 patients served as untreated controls. There was a six-month post-treatment follow-up. Two patients in the treatment group and one in the control group had to be excluded later. In the treatment group one patient responded completely (HBs antigen, HBe antigen and HBV-DNA negative) and eight partially (HBe antigen and HBV-DNA negative). In three patients of the control group, HBe antigen and HBV DNA were no longer demonstrated (P less than 0.05). The loss of HBV features was associated with normalization of serum transaminases activity. Reactivation of liver inflammation after seroconversion was not observed.

Adolescent↗

Terminal deletion 6p23: a case report.

We report on a girl with cleft lip and cleft palate, antimongoloid slant of the palpebral fissures, umbilical hernia, skeletal anomalies, partial syndactyly, hypertonia with increased deep tendon reflexes, psychomotor and growth retardation, and other congenital anomalies. Cytogenetic studies demonstrated a 46,XX,del(6)(qter----p23:) chromosome constitution.

Abnormalities, Multiple↗