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Biomedical subjects

B Hoffmann

Publications and source records attributed to B Hoffmann.

At least 145 records · Page 8Linked to original sources
PubMed1993

Secretion and release of luteinizing hormone during the luteal phase of the oestrous cycle in the dog.

In order that the luteotrophic activity of luteinizing hormone (LH) in the dog might be more precisely elucidated, LH and progesterone were measured in blood samples collected at intervals of 10-15 min over 360 min from three beagle and two foxhound-boxer bitches at a defined day during pro-oestrus, the phase immediately after ovulation, early and late dioestrus and early anoestrus. In addition, the three beagle bitches were treated with the gonadotrophin-releasing hormone (GnRH) analogue buserelin at a given day during each quarter of dioestrus and blood was sampled over 480 min at intervals of 15 min (for 2 h), 30 min (for 4 h) and 60 min (for 2 h). Cyclic activity was monitored by determining progesterone at intervals of 1 or 2 days up to 140 days. In spite of some apparently breed-specific differences, the results indicated that the availability of LH depended on the stage of the cycle. The area under the curve (AUC) was higher during pro-oestrus, late dioestrus and early anoestrus (P < 0.01-0.05), largely as a result of an increased pulse amplitude and not of changes in basal concentrations or pulse frequency. After GnRH the AUC for the provoked LH release increased from 1206 ng (150 min) ml-1 (first quarter) to 4045 ng (150 min) ml-1 (fourth quarter) (P < 0.01); maximum LH values were reached between 25 and 40 min. In neither experiment did progesterone increase during the observation periods of 360 and 480 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Regulatory gene INO4 of yeast phospholipid biosynthesis is positively autoregulated and functions as a transactivator of fatty acid synthase genes FAS1 and FAS2 from Saccharomyces cerevisiae.

The sequence motif 5' TYTTCACATGY 3' functions as an upstream activation site common to both yeast fatty acid synthase genes, FAS1 and FAS2. In addition, this UASFAS element is shared by all so far characterized genes of yeast phospholipid biosynthesis. We have investigated the influence of a functional INO4 gene previously described as a regulator of inositol biosynthesis on the expression of FAS1 and FAS2. In a delta ino4 null allele strain, both genes are expressed at only 50% of wild type level. Using individual UASFAS sequence motifs inserted into a heterologous test system, a drastic decrease of reporter gene expression to 2-10% of the wild type reference was observed in the delta ino4 mutant. In gel retardation assays, the protein-DNA complex involving the previously described FAS binding factor 1, Fbf1, was absent when using a protein extract from the delta ino4 mutant. On the other hand, this signal was enhanced with an extract from cells grown under conditions of inositol/choline derepression. Subsequent experiments demonstrated that INO4 expression is itself affected by phospholipid precursors, mediated by an UASFAS element in the INO4 upstream region. Thus, in addition of being an activator of phospholipid biosynthetic genes, INO4 is also subject to a positive autoregulatory loop in its own biosynthesis.

Base Sequence↗
PubMed1992

A retinoic acid response element from the rat CRBPI promoter is activated by an RAR/RXR heterodimer.

The expression of the rat cellular retinol binding protein I (rCRBPI) can be upregulated in vivo by retinoic acid (RA). Here we have analyzed the rCRBPI promoter region and compared it to the corresponding mouse sequence. We find that the CRBPI 5' flanking region has been highly conserved between rat and mouse, including a RA response element (RARE) approximately 1 kb upstream of the start of transcription. The RARE is of the direct repeat type with a two nucleotide spacer. Like other direct repeat RAREs, this response element is activated by RAR alpha and beta but not by RAR gamma 1. Furthermore, the rCRBPI-RARE is most effectively activated when both RAR and RXR are present. In addition RAR/RXR heterodimers are required for efficient binding to the rCRBPI-RARE, while RARs or RXR alone do not interact effectively with this response element. The rCRBPI gene is therefore most likely activated in vitro by a RAR/RXR heterodimer.

Animals↗
PubMed1992

Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid.

Retinoid response pathways are mediated by two classes of receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). A central question is whether distinct response pathways are regulated by these two classes of receptors. The observation that the stereoisomer 9-cis-retinoic acid binds with high affinity to RXRs suggested that this retinoid has a distinct role in controlling RXR activity, but it was almost simultaneously discovered that RXRs function as auxiliary receptors for RARs and related receptors, and are essential for DNA binding and function of those receptors. Hence, although RARs seem to operate effectively only as heterodimeric RAR/RXR complexes, RXRs themselves apparently function predominantly, if not exclusively, as auxiliary receptors. Here we report that 9-cis-retinoic acid induces RXR homodimer formation. Our results demonstrate a new mechanism for retinoid action by which a ligand-induced homodimer mediates a distinct retinoid response pathway.

Animals↗
PubMed1992

Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors.

Thyroid hormones and retinoic acid function through nuclear receptors that belong to the steroid/thyroid-hormone receptor superfamily. Thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) require auxiliary nuclear proteins for efficient DNA binding. Here we report that retinoid X receptors RXR alpha is one of these nuclear proteins. RXR alpha interacts both with TRs and with RARs, forming heterodimers in solution that strongly interact with a variety of T3/retinoic acid response elements. Transfection experiments show that RXR alpha can greatly enhance the transcriptional activity of TR and RAR at low retinoic acid concentrations that do not significantly activate RXR alpha itself. Thus, RXR alpha enhances the transcriptional activity of other receptors and its own ligand sensitivity by heterodimer formation. Our studies reveal a new subclass of receptors and a regulatory pathway controlling nuclear receptor activities by heterodimer formation.

Animals↗
PubMed1992

Subarachnoid hemorrhage of unknown origin. Longterm prognosis.

Patients suffering subarachnoid hemorrhage in whom angiography does not initially show vascular malformation and CT scan rules out an intracranial tumor, have, reportedly, a good prognosis with a rate of recurrent hemorrhage of about 2-10% within a follow-up time of up to 15 years. Most authors denied indication for control angiography. In order to study the benefit of control angiography performed after 4-6 weeks, four-hundred eighty-three patients with SAH but without ICH were reveiwed, and the longterm clinical course of 98 patients with SAH of unknown origin treated in our department between 1976 and 1988 was investigated. Among 183 patients who underwent control angiography, a second angiography showed an aneurysm in 143. The third angiography was positive in a further 18 patients. Recurrent SAH occurred early only in patients who had undergone only one angiography. One patient died from intracerebral hemorrhage of unknown origin two years following SAH. These data support the need for control angiography in cases of SAH.

Adolescent↗
PubMed1992

Current management of male breast cancer. A review of 104 cases.

Between 1975 and 1990, 104 male patients with a total of 106 breast cancers were treated at Memorial Hospital or the Ochsner Clinic and their records reviewed. The patients were followed for a median of 67 months (range, 0.5 to 14.4 years). Analysis of the frequency distribution by stage showed that 16 (17%) patients were stage 0 and 26 (27%) patients were stage I. The median duration of symptoms before diagnosis was 18 weeks (mean, 5 weeks; range, 1 to 156 weeks). Modified radical mastectomy was undertaken in 71 (67%) patients. The actuarial 5-year relapse-free survival for the entire group was 68% and the actuarial 5-year overall survival was 85%. Relapse-free survival at 5 years for axillary node-negative patients was 87% and for node-positive patients was 30% (p less than 0.001). Overall survival figures for the same subsets showed a 5-year survival of 100% for the node-negative subset and 60% for the node-positive subset. On multivariate analysis, the most powerful predictor of outcome in men was the status of the axillary lymph nodes, and the only prognostic factor that added significantly to this predictive power was the duration of symptoms. Patients who sought treatment less than 6 months after the onset of symptoms experienced a significant survival advantage when compared with patients whose symptoms were present for more than 6 months (p = 0.03). The profile of the stages at diagnosis, the treatment approach, and the survival rates approximate those reported in series of female breast cancers, and overall, the two diseases are remarkably similar.

Actuarial Analysis↗
PubMed1992

Heterodimeric receptor complexes determine 3,5,3'-triiodothyronine and retinoid signaling specificities.

Thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) have been shown to interact with nuclear auxiliary proteins resulting in heteromeric complexes that bind strongly to their responsive elements. Recently the retinoid X receptors (RXRs) have been identified as one class of these nuclear proteins. RXRs strongly increase binding of TRs and RARs to a synthetic thyroid hormone (and retinoic acid) responsive element. Here results show that the binding of the heteromeric complexes to various natural response elements is highly specific and dictated by the partner of RXR in the complex. TR alpha and TR beta formed complexes with RXR alpha that strongly and selectively bound to natural thyroid hormone responsive elements, i.e. those from the rat alpha-myosin heavy chain gene and the rat malic enzyme gene. RXR alpha complexes with RAR alpha, RAR beta, and RAR gamma bound selectively to retinoic acid responsive elements from the human RAR beta 2 gene (hRAR beta 2), the gene of the rat cellular retinol binding protein I and the human apolipoprotein A1 gene. Under the conditions used here RXR alpha by itself did not bind to any of the responsive elements tested. Although TRs and RARs formed heterodimers with RXR in solution, these complexes were strongly stabilized by specific, high affinity response elements, but not by low affinity response elements. Transfection analyses showed strong synergism between receptors that formed effective heterodimers in transcriptional activation on several but not all response elements. Overall, these data demonstrate that RARs and TRs are unlikely to function as monomers or homodimers on the response elements investigated here and require RXRs or comparable proteins for effective response element activation.

Animals↗
PubMed1992

Ovarian and pituitary function in dogs after hysterectomy.

In studies of five hysterectomized and five control dogs, hysterectomy shortened the anoestrous interval (96.6 +/- 28.0 versus 149.4 +/- 50.9 days, P < 0.05). No differences in hormone concentrations (progesterone, oestradiol, prolactin and growth hormone) were observed between the control and hysterectomized dogs except for a brief fall in progesterone concentrations over 8 days immediately after surgery, between days 35 and 40 after onset of pro-oestrous bleeding; only these animals developed symptoms of overt pseudopregnancy. It is concluded that, in dogs, luteal regression occurs independently of a uterine luteolysin, but that the uterus may play a role in control of duration of anoestrus. Pseudopregnancy seems to be initiated by a fall in progesterone concentrations rather than by other hormonal changes.

Analysis of Variance↗
PubMed1991

Identification of NolR, a negative transacting factor controlling the nod regulon in Rhizobium meliloti.

In Rhizobium meliloti, expression of the nodulation genes (nod and nol genes) is under both positive and negative controls. These genes are activated by the products of the three related nodD genes, in conjunction with signal molecules from the host plants. We showed that negative regulation is mediated by a repressor protein, binding to the overlapping nodD1 and nodA as well as to the nodD2 promoters. The encoding gene, termed nolR, was identified and cloned from strain 41. By subcloning, deletion and Tn5 mutagenesis, a region of 594 base-pairs was found to be necessary and sufficient for repressor production in strains of R. meliloti lacking the repressor or in Escherichia coli. Sequence analysis revealed that nolR encodes a 13,349 Da protein, which is in agreement with the molecular weight of the NolR protein, determined after purification by affinity chromatography, utilizing long synthetic DNA multimers of the 21 base-pair conserved repressor-binding sequence. Our data suggest that the native NolR binds to the operator site in dimeric form. The NolR contains a helix-turn-helix motif, which shows homology to the DNA-binding sequences of numerous prokaryotic regulatory proteins such as the repressor XylR or the activator NodD and other members of the LysR family. Comparison of the putative DNA-binding helix-turn-helix motifs of a large number of regulatory proteins pointed to a number of novel regularities in this sequence. Hybridizations with an internal nolR fragment showed that sequences homologous to the nolR gene are present in all R. meliloti isolates tested, even in those that do not produce the repressor. In another species, such as Rhizobium leguminosarum, where NodD is autoregulated, however, such sequences were not detected.

Amino Acid Sequence↗
PubMed1991

Genomic organization of the retinoic acid receptor gamma gene.

The retinoic acid receptors (RAR) belong to the large family of ligand responsive gene regulatory proteins that includes receptors for steroid and thyroid hormones. These proteins contain two highly conserved domains, involved in determining their DNA and ligand binding activities. Three distinct RARs have been identified (RAR alpha, beta, and gamma) which are encoded by genes on separate chromosomes. Additional isoforms of the three receptors have been described that all differ in the N-terminal regions. To gain insight into the genomic organization and mechanisms of RAR isoform generation, we have analyzed the genomic structure of the RAR gamma gene. The major portion of the RAR gamma protein, including DNA and ligand binding domains, is encoded by seven exons that are identical for all RARg isoforms and are represented by a relatively small portion of the RAR gamma gene. The major portion of this gene encodes separate N-terminal exons for gamma 1 and gamma 2 isoforms and several exons for gamma 1 untranslated regions. We show that RAR gamma 2 transcription is regulated by its own promoter. In comparison with the steroid receptor subfamily, various splice sites of RAR gamma occur at altered positions, suggesting that the RAR subfamily has diverged early during evolution.

Amino Acid Sequence↗
PubMed1991

Different modes of electrogenic Na+ absorption in the coprodeum of the chicken embryo: role of extracellular Ca2+.

Transepithelial electrogenic Na+ transport (INa) was investigated in the coprodeum of 20-days-old chicken embryos in Ussing chambers. Short circuit current (Isc) and transepithelial resistance (Rt) were 14.7 +/- 4.8 microA.cm-2 (n = 12) and 0.53 +/- 0.09 k omega.cm-2 (n = 12), respectively. INa was calculated from changes in Isc by substitution of mucosal Na+ by (N-methyl-D-glucamine) (NMDG). Isc inversed during Na+ removal, and INa was found to be 27.8 +/- 4.7 microA.cm-2 (n = 12). Amiloride (100 mumol.l-1) inhibited only about 60% of INa. Analysis of Isc fluctuations revealed a Lorentzian component in the power density spectrum with a corner frequency of about 57 Hz. This component was not correlated to INa, and its origin is still unclear. Removal of mucosal Ca2+ increased INa about 2.5-fold due to an increase of the amiloride-insensitive component of INa in additionally investigated adult tissues. The results clearly show that this is due to a non-selective cation channel with an "apparent" order of selectivity Cs+ greater than Na+ = K+ greater than Rb+ greater than Li+. The Ca2+ concentration required to block 50% of the Isc was about 18 mumol.l-1. The IscCa could also be suppressed by other divalent cations such as Mg2+ and Ba2+. Additionally, an INa-linked Lorentzian component occurred which dominated the control spectrum with a significantly higher corner frequency (about 88 Hz). The results indicate that Na+ absorption in the coprodeum of the chicken embryo is more complex than in adult hens.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1991

Indication for invasive diagnostic studies and surgical therapy in cerebral ischemia, based on results of non-invasive transcranial Doppler sonography.

In order to better define patients who might benefit from cerebral revascularization surgery, transcranial Doppler sonography was used in more than 480 patients. Thus invasive diagnostic studies could be limited to probable surgical candidates. Transcranial Doppler sonography has proven to be reliable for the study of the degree of efficacy of intracranial collateral pathways in hemodynamic borderline situations. Over the last 4 years, the application of the algorithm presented in this paper resulted in a reduction of the number of candidates for surgical revascularization to 19.

Algorithms↗
PubMed1991

Involvement of the syrM and nodD3 genes of Rhizobium meliloti in nod gene activation and in optimal nodulation of the plant host.

We identified and sequenced the regulatory syrM and nodD3 genes of Rhizobium meliloti 41. Both genes were shown to contribute to optimal nodulation of alfalfa. In R. meliloti strains carrying syrM and nodD3 on plasmid, the nod genes are expressed constitutively, resulting in host-range extension to siratro. This is due to the presence of multiple syrM copies, suggesting that SyrM participates directly in nod gene activation. NodD3 activates nod genes in conjunction with flavonoids and enhances syrM expression, which is controlled also by its own product, NodD2, and two putative trans-acting factors. nodD3 is regulated by SyrM, NodD1, nodD3, the repressor NoIR, and two putative factors.

Amino Acid Sequence↗
PubMed1991

Antagonism between retinoic acid receptors.

In the developing mouse, retinoic acid receptors (RARs) beta and gamma 1 are expressed in characteristic spatiotemporal patterns which are correlated with different developmental fates of the respective tissues. Understanding the cues that regulate the expression of the various RARs may therefore provide insights into the process of tissue diversification. Transcription of RAR beta is rapidly upregulated through a retinoic acid-responsive element (here referred to as the beta RARE) in its promoter. Like RAR alpha and RAR beta, RAR gamma 1 has been implicated in the activation of the beta RARE. Therefore, it is puzzling that RAR beta and RAR gamma 1 appear to be expressed in reciprocal patterns. In the present report, we show that RAR gamma 1, one of the two predominant RAR gamma isoforms, can inhibit the activity of RAR gamma 2, RAR beta, and endogenous RAR on the beta RARE. In contrast, the three RAR gamma isoforms tested and RAR beta activated a palindromic thyroid hormone response element with similar levels of efficiency. The differential activity of RAR gamma 1 compared with that of RAR beta appears to reside in both the N-terminal and the C-terminal halves of RAR gamma 1. RAR gamma 1-mediated inhibition of other RARs may involve competition for the response element as well as direct interaction with other receptors and might be part of a regulatory system contributing to the characteristic tissue distribution of the various RARs.

Animals↗
PubMed1991

Improved purification and characterization of membraneous and cytosolic inositol phospholipid-specific phospholipases C from porcine brain cortex.

A phospholipase C was solubilized and purified from membranes of porcine brain cortex. Simultaneously, a phospholipase C was purified from a cytosolic fraction of porcine brain cortex. The enrichment of phospholipase C from either fraction was about 1000-fold as determined by hydrolysis of phosphatidylinositol 4,5-bisphosphate. Phospholipases C purified from membranes or from cytosol were indistinguishable with regard to the following properties: The enzyme activities copurified with a protein of 145 kDa. The standard sedimentation coefficients (s20,w values) of the purified enzymes were 6.2 S in the absence or presence of 0.3% (w/v) sodium cholate; Stokes' radii, estimated by gel filtration on a Superose 6 HR 10/30 column in the presence of 0.3% sodium cholate, were 4.5 nm; calculated molecular masses were about 120 kDa; no significant hydrolysis of phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine by preparations of purified phospholipase C was observed; adenine and guanine nucleotides affected the activity of purified enzymes in a complex manner. Thus, the enzymes purified from membraneous and from cytosolic fractions exhibited properties of the phospholipase C-beta form. The enzymes purified from either fraction required Ca2+ at a low concentration (100 nM to 10 microM) for maximal activity. The advantage of the present purification procedure is that the purified enzymes were free of phosphatidylinositol 4,5-bisphosphate 5-phosphatase, inositol 1,4,5-trisphosphate 5-phosphatase and guanine nucleotide-binding proteins after three chromatographic steps. The purified enzymes may, therefore, prove useful for studying the hormonal regulation of phospholipase C in reconstituted systems and for the preparation of [5-32P]inositol 1,4,5-trisphosphate from [5-32P]phosphatidylinositol 4,5-bisphosphate.

Animals↗