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Biomedical subjects

F Beck

Publications and source records attributed to F Beck.

At least 37 records · Page 2Linked to original sources

Effects of long-term changes in medullary osmolality on heat shock proteins HSp25, HSP60, HSP72 and HSP73 in the rat kidney.

The influence of diuresis and antidiuresis on the expression of heat shock proteins (HSP) 25, 60, 72 and 73 in the renal cortex and outer and inner medulla of Wistar rats was analysed. Medullary osmolality was reduced by long-term diuresis (3% sucrose in the drinking water for 3 weeks) and subsequently enhanced by transition to a concentrating state by giving normal drinking water again in combination with deamino-D-arginine vasopressin (dDAVP) for 5 days. Western blot analyses revealed that neither HSP73 nor HSP60 was influenced by any treatment. The HSP72 level in the medulla was markedly reduced (50%) when osmolality was lowered and increased when tonicity was high. RNAse protection assays showed that the effects on HSP72 are parallelled in general by changes in HSP72 mRNA. While levels of HSP25 were not influenced, isoelectric focusing revealed that the degree of phosphorylation of outer and inner medullary HSP25 increased following both treatments. It thus seems that HSP73 and HSP60 are not directly involved in the long-term adaptation to varying medullary osmolalities. The correlation between changes in osmolality and amounts of the major stress-inducible HSP72 in the medulla implies that medullary hypertonicity is stressful for kidney cells. Furthermore, adaptation to pronounced changes in the osmolality of the environment most likely involves phosphorylation of HSP25.

Animals↗

Comparison of transesophageal Doppler methods with angiography for evaluation of the severity of mitral regurgitation.

Doppler evaluation of mitral regurgitation remains difficult; thus, a head-to-head comparison of the diagnostic accuracy of Doppler methods was undertaken. Fifty patients with native mitral regurgitation underwent multiplane transesophageal echocardiography within 5 days of catheterization. Angiographic grade of mitral regurgitation and, in 20 patients with grade II-IV regurgitation, invasively determined regurgitant stroke volume were compared with color Doppler area, regurgitant jet diameter, ratio of systolic to diastolic peak pulmonary venous flow velocities, and (based on the proximal convergence zone) maximal regurgitant flow rate and regurgitant orifice area. Rank correlation coefficients of angiographic grade with Doppler parameters were 0.61 for color jet area, -0.61 for pulmonary venous flow velocity ratio, 0.69 for color jet diameter, 0.79 for maximal regurgitant flow rate, and 0.78 for regurgitant orifice area (all P < .01). Convergence zone-based parameters also correlated best (r=0.73) with invasively determined regurgitant stroke volume. Receiver operating characteristic curve analysis confirmed higher diagnostic accuracy for proximal jet width and proximal convergence zone parameters than for color jet area or pulmonary venous flow velocity ratio. Proximal convergence zone parameters and proximal color jet diameter best distinguished severe from mild forms of mitral regurgitation.

Cardiac Catheterization↗

Developmental biology at the Howard Florey Institute.

1. A brief account of the history of developmental biology at the Howard Florey Institute, as well as in a wider general context, is presented and some of the results of developmental studies performed at the Institute over the past 7 years are discussed. 2. In the foetal rat, parathyroid hormone rather than parathyroid hormone-related protein is produced by the parathyroid anlage. This contrasts with results reported by others for the sheep. 3. The control of imprinting of H19 and insulin-like growth factor-II has been studied in the mouse using gene knockout of the coding region of the H19 gene. Bi-allelic expression of H19 in some liver and gut cells was observed. 4. Gene knockout of the homeobox gene Cdx2 produced dramatic effects. Homozygous embryos did not implant in the uterus. Heterozygotes exhibited homeosis involving the gut and skeleton. Animals developed intestinal tumours within a few weeks of birth.

Academies and Institutes↗

Expression of parathyroid hormone-related protein (PTHrP) and the PTH/PTHrP receptor in the rat uterus during early pregnancy and following artificial deciduoma induction.

The interaction between parathyroid hormone-related protein (PTHrP) and the parathyroid hormone (PTH)/PTHrP receptor is thought to play a role in the growth and differentiation of various tissues throughout fetal development in the rodent. The aim of the present study was to define the patterns of expression of PTHrP and of the PTH/PTHrP receptor in the rat uterus during the early stages of normal pregnancy, and following artificial induction of a decidual reaction. Using hybridization histochemistry, we have shown that the receptor gene is switched on early in pregnancy (by 1.5 days post coitum) in the endometrial stromal cells that surround the lumen. These cells include the anti-mesometrial subepithelial stromal cells that are destined to become decidualized. This pattern continues until 5.0 days post coitum, when PTHrP is switched on in antimesometrial luminal epithelial cells that line the implantation chamber. Stromal cells underlying the implantation chamber then downregulate transcription of the receptor gene, and within 12 h differentiate into decidual cells. A similar pattern was seen in uteri in which a decidual reaction had been induced artificially. Therefore, it may be postulated that in early pregnancy the endometrial stroma initiates transcription of the gene for the PTH/PTHrP receptor and is thus 'primed' for the PTHrP signal from the luminal epithelial cells. Some time after receiving the signal, the endometrial stromal cells downregulate the receptor gene, and this appears to be a trigger for the terminal differentiation of the stromal cells into decidual cells. These results suggest that PTHrP, acting through the PTH/PTHrP receptor, plays a role in the initiation of a decidual reaction during early pregnancy by regulating the differentiation of endometrial stromal cells into decidual cells.

Animals↗

[Compression of the celiac trunk by the diaphragmatic arcuate ligament during supramesocolonic surgery].

Coeliac stenosis induced by arcuate ligament compression is usually asymptomatic. Current caution is advised during a supramesocolonic surgical procedure in the case of a collateral arterial system due to coeliac stenosis. 11 cases of coeliac stenosis are described. 3 patients underwent duodenopancreatic resection, 8 patients had liver transplantation. 2 patients died after complications due to celiac, stenosis. These cases are described. The authors discuss the diagnostic and therapeutic approach.

Adult↗

Homeosis and intestinal tumours in Cdx2 mutant mice.

In Drosophila, disturbing the expression of the homeobox gene caudal causes a severe disruption in body segmentation and global body patterning. There are three mouse homologues of Drosophila caudal: Cdx1 (ref. 2), Cdx2 (ref. 3) and Cdx4 (ref. 4). We have generated a null mutation of murine Cdx2 by homologous recombination. Cdx2 homozygote null mutants die between 3.5 and 5.5 days post coitum (d.p.c.). Cdx2 heterozygote mutants exhibit a variable phenotype, with many showing tail abnormalities or stunted growth. Skeletal analysis demonstrates a homeotic shift of vertebrae and compatible malformations of the ribs. Within the first three months of life, 90% of Cdx2 heterozygotes develop multiple intestinal adenomatous polyps, particularly in the proximal colon. These polyps occasionally contain areas of true metaplasia. In contrast to the surrounding intestinal epithelium, the neoplastic cells do not express Cdx2 from the remaining allele. These results suggest that Cdx2 mutation is the primary event in the genesis of some intestinal tumours.

Adenomatous Polyposis Coli↗

A search for a mammalian homologue of the Drosophila photoreceptor development gene glass yields Zfp64, a zinc finger encoding gene which maps to the distal end of mouse chromosome 2.

Whilst searching for a mammalian homologue of the Drosophila glass gene we cloned a mouse cDNA whose deduced sequence encodes a 614 amino acid (aa) protein with ten Cys2-His2 (C2H2) zinc finger (Zf) motifs. Zfp64 is expressed in all developing and mature mouse tissues examined, except the mouse erythroleukemia (MEL) cell line. Zfp64 maps to the distal region of mouse chromosome 2 close to lens opacity 4 (Lop4), a semidominant cataract mutation. Sequence analysis shows that Zfp64 has multiple potential phosphorylation sites for casein kinase II (CK II), protein kinase C (PKC), tyrosine kinase (TK) and c-AMP- and c-GMP-dependent protein kinase (cA/GMPDPK).

Amino Acid Sequence↗

Solute composition and heat shock proteins in rat renal medulla.

The high content of heat shock proteins (HSPs) 25 and 72 in the hyperosmotic inner medulla of the concentrating kidney has been ascribed to the high NaCl and urea concentrations in this kidney zone. To assess the effects of variations in the composition of solutes in the renal medulla on the intrarenal distribution of HSPs, rats were fed either a high- or low-Na diet for 3 weeks. These diets result in greatly differing urine and inner medullary solute composition. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot techniques were used to analyse HSP25 and HSP72 in the cortex, outer medulla and inner medulla. In addition, the amounts of organic osmolytes (sorbitol, myo-inositol, betaine and glycerophosphorylcholine) and urea in the tissue were determined by high-performance liquid chromatography. Intra- and extracellular electrolyte concentrations at the papillary tip were measured by electron microprobe analysis. In the high-Na group, urine osmolality was about 1000 mosmol/kg lower than in rats fed a low-Na diet, due to lower urea concentrations. The sum of urine sodium and potassium concentrations, however, did not differ between the two groups. Neither in the outer nor in the inner medulla was the sum of the concentrations of organic osmolytes affected by the dietary treatment. The sum of sodium, potassium and chloride concentrations did not differ between the two experimental groups, neither in the interstitial nor in the intracellular compartments. However, the urea content and the amounts of HSP25 and HSP72 were significantly lower in the inner medulla of the group of rats fed a high-Na diet. Our results suggest that urea participates in the regulation of the medullary levels of the HSPs and that both HSP25 and HSP72 are components of mechanisms protecting medullary cells against the deleterious effects of high urea concentrations.

Animals↗

[Severe digital ischemia disclosing Basedow's disease: 2 cases].

We report two observations of young women with concomitant diagnosis of acute arterial occlusion of the upper limb and Graves' disease. The occlusion was probably related to arterial embolism on paroxysmal atrial fibrillation, without underlying cardiopathy. Dosage of thyroid hormones should be performed in case of arterial occlusion in young subjects without cardiovascular risk factors.

Acute Disease↗

The effect of antisense oligonucleotides to Cdx2 on the development of mouse embryos in vitro.

The Drosophila homeobox gene caudal is thought to play a role in segmentation and the formation of posterior structures in the fly. One of the mouse homologs, Cdx2, is first expressed in embryonic tissue at 8.5 days, being detected in the tail bud, neural tube and hindgut. To gain insight into the role of Cdx2 in mouse development, we have applied antisense technology to the mouse embryo culture system. Two antisense and two mismatch (control) oligonucleotides were injected into the amniotic cavity of 5-7 somite embryos, thus coming into direct contact with the dorsal surface of the embryo. The results showed that all constructs were biologically active, the nature of the abnormalities produced probably reflecting the developmental stage at which the embryo was exposed. However, the antisense constructs were clearly more potent than their mismatch controls and we conclude that some specificity of action is responsible for this effect. In our view, this does not necessarily imply that Cdx2 has a direct role in brain morphogenesis.

Animals↗

Characterization of two conformational epitopes of the Chlamydia trachomatis serovar L2 DnaK immunogen.

Chlamydia trachomatis DnaK is an important immunogen in chlamydial infections. DnaK is composed of a conserved N-terminal ATP-binding domain and a variable C-terminal peptide-binding domain. To locate the immunogenic part of C. trachomatis Dnak, we generated monoclonal antibodies (MAbs) against this protein. By use of recombinant DNA techniques, we located the epitopes for two MAbs in the C-terminal variable part. Although the antibodies reacted in an immunoblot assay, it was not possible to map the epitopes completely by use of 16-mer synthetic peptides displaced by one amino acid corresponding to the C-terminal part of C. trachomatis DnaK. To determine the limits of the epitopes, C. trachomatis DnaK and glutatione S-transferase fusion proteins were constructed and affinity purified. The purified DnaK fusion proteins were used for a fluid-phase inhibition enzyme-linked immunosorbent assay with the two antibodies. The epitopes were found not to overlap. To obtain DnaK fragments recognized by the antibodies with the same affinity as native C. trachomatis DnaK, it was necessary to express, respectively, regions of 127 and 77 amino acids. The MAbs described in this study thus recognized conformational epitopes of C. trachomatis DnaK.

Adenosine Triphosphatases↗

Can quantum processes control synaptic emission?

The role of quantum processes in brain activity has been discussed intensively in recent years. Some authors regard the indeterminacy of quantum events as key property to relate brain activity and consciousness on a scientific basis. Here we ask the question where quantum events could be effective in the complex cortical structure. We argue that only elementary microscopic processes like electron transfer in protein complexes are able to survive thermal fluctuations. A model for the quantal emission process at the synaptic cleft is presented and related to the mechanism of electron transfer between different molecular states, as described by Marcus theory.

Brain↗

The expression of parathyroid hormone and parathyroid hormone-related protein in developing rat parathyroid glands.

Secretion of parathyroid hormone-related protein (PTHrP) by sheep fetal parathyroid glands is reported to be an important factor in the maintenance of a placental calcium pump. The aim of the present study was to determine whether the developing rat parathyroid glands express PTHrP or parathyroid hormone (PTH), or both. Hybridisation histochemistry was used to detect transcription of PTHrP and PTH in serial paraffin sections through the 12.5- and 13.5-day rat embryo parathyroid anlage, as well as in sections through the 17.5-day embryonic and adult parathyroid glands. Results show strong expression of PTH in the 13.5-day embryonic parathyroid anlage, as well as in the parathyroid gland of the 17.5-day embryo and adult. Transcription of the PTHrP gene was not detected. The more sensitive technique of reverse transcription PCR was then performed. The pharyngeal region of 11.5-, 12.5- and 13.5-day rat embryos was dissected out and, at each stage, RNA was extracted from these tissues, as well as pooled tissues from the rest of the embryo. RNA that had been extracted from adult thyroid/parathyroid tissue was also tested. After reverse transcription, the resulting cDNAs were amplified by PCR (50 cycles) using specific PTH and PTHrP primers. The results show an abundance of PTH mRNA, specific to the pharyngeal region of the 13.5-day embryo, as well as to adult thyroid/parathyroid tissue. PTHrP expression was detected at very low levels in both parathyroid and extraparathyroid tissues. The presence of immunoreactive PTHrP and immunoreactive PTH in the pharyngeal region and rest of the body of 12.5- and 13.5-day rat embryos was assessed by specific RIAs. Whilst immunoreactive PTHrP was not detected in any of the tissues assayed, immunoreactive PTH was detected only in the pharyngeal region of the 13.5-day embryo. This confirms the results obtained from the gene expression studies. We conclude then that, in the developing rat embryo, PTH rather than PTHrP is more likely to play a role in calcium regulation. This is in contrast with the reported situation in the sheep, and suggests that fundamental species differences in fetal calcium regulation exist in mammals.

Aging↗

The role of fetal parathyroid hormone-related protein in transplacental calcium transport.

During pregnancy, a placental calcium pump maintains the fetus in a hypercalcaemic state relative to the mother, a condition which has been thought to facilitate normal development of the fetal skeleton. Based on experiments performed in the sheep, parathyroid hormone-related protein (PTHrP) has been implicated as the hormone responsible for maintaining the placental calcium pump. In the present study on mice in which the PTHrP gene has been ablated by homologous recombination, we have measured both fetal and maternal circulating total and ionised calcium levels, as well as fetal total body calcium, in order to determine whether absence of PTHrP during fetal development has an effect on fetal calcium levels. Our results show that, in fetuses lacking PTHrP, circulating ionised calcium levels are significantly lower than those of heterozygote and wild-type littermates, but circulating total calcium levels show no difference. Total body calcium levels of null mutants are significantly higher than those of normal littermates. The role of PTHrP in maintaining the integrity of the transplacental calcium pump in the rodent thus remains unclear. It may be that the lower levels of fetal blood ionised calcium in mutant animals are due to disruption of the placental pump, but, if this is the case, compensatory mechanisms have operated to allow the excessive calcium deposition seen in the skeletons of these animals. Alternatively, the increased avidity of the bones for calcium may in itself have produced a lower equilibrium level of available ionised calcium.

Animals↗