Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors

Truncated activin type II receptors have been reported to inhibit activin receptor signaling in Xenopus embryos, although the mechanism of action for this effect has not been fully understood. In the present study we demonstrate that in P19 embryonal carcinoma cells both the induction of the activin responsive 3TP-lux reporter construct and the inhibition of retinoic acid-induced neuronal differentiation by activin are blocked by expression of a truncated activin receptor. To reveal the mechanism of action of truncated activin receptors, the interaction between different activin receptors has been investigated upon coexpression in COS cells followed by cross-linking of 125I-activin A and subsequent immunoprecipitation. Complexes between a truncated activin type IIA receptor and activin type IA and type IB receptors can be formed, as demonstrated by coimmunoprecipitation of these type I receptors with the truncated activin type IIA receptor. Other type I receptors known as ALK-1 and ALK-6 also coimmunoprecipitate with the truncated type IIA receptor, whereas ALK-3 and ALK-5 do not. Furthermore, the activin type IIB2 receptor does not coimmunoprecipitate with the truncated type IIA receptor, but decreases activin binding to the truncated type IIA receptor. In double immunoprecipitation experiments with cell lysates from COS cells, in which full-length activin type IIA and type IIB2 receptors were cotransfected, no interaction between these receptors was found. In contrast, homomeric complexes of full-length activin type IIA receptors were detected. These results implicate that truncated activin receptors can interfere with activin signaling by interacting with activin type I receptors. Additionally, truncated activin type IIB2 receptors might also interfere with type IIA receptor signaling by decreasing activin binding to the type IIA receptor and therefore might be more potent in inhibiting activin signal transduction. Furthermore, our data indicate that truncated type IIA receptors can interact with other type I receptors and as such might inhibit signal transduction by type I receptors other than activin type IA and type IB receptors.     

Effect of protein content on low temperature inactivation of the extracellular proteinase from Pseudomonas fluorescens 22F

The formation of cholic acid and chenodeoxycholic acid through cleavage of the side chains of CoA esters of 3alpha,7alpha,12alpha-trihydroxy-5beta-choles tan-26-oic acid and 3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid is believed to occur in peroxisomes. Recently, we found a new peroxisomal enzyme, D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein, and suggested that this bifunctional protein is responsible for the conversion of 3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-2 4-en-26-oyl-CoA and 3alpha,7alpha-dihydroxy-5beta-cholest-24-en-26-oyl-CoA to their 24-oxo-forms. In the present study, the products of this bifunctional protein reaction were analyzed by gas chromatography-mass spectrometry, and the formation of 24-oxo-27-nor-cholestanes was confirmed. Previously, we found a new thiolase in Caenorhabditis elegans, P-44, and suggested that P-44 and sterol carrier protein x, a peroxisomal protein, constitute a second group of 3-oxoacyl-CoA thiolases. The production of cholic acid and chenodeoxycholic acid from the precursors on incubation with the bifunctional protein and sterol carrier protein x or P-44 was confirmed by gas chromatography.     

Right-sided sciatalgia complicating Crohn's disease

Neurological complications of Crohn's disease due to involvement of the extradural space are extremely rare. A 40-yr-old woman with Crohn's disease affecting the terminal ileum presented with a right-sided sciatalgia. The patient did not complain of diarrhea or constipation. The serum fibrinogen and the C-reactive protein were elevated. Magnetic resonance imaging and computed tomography scan of the abdomen and pelvis demonstrated a mass in front of the sacrum up to but not including the first sacral vertebra. Surgical intervention, with resection of 15 cm of terminal ileum, led to the complete resolution of symptoms. In this case, the underlying cause of the neurological symptoms was most likely an infiltration of the right lumbosacral nerve caused by edema and inflammation of the terminal ileum in the vicinity of the presacral space. Unexplained lumbosacral neurological symptoms in a patient with Crohn's disease necessitate a magnetic resonance imaging or computed tomography scan to detect potential neurological compression.     

Chemical denaturation and modification of ovalbumin alters its dependence on ubiquitin conjugation for class I antigen presentation

Class I presentation of microinjected native OVA by a temperature-sensitive ubiquitin conjugation mutant, ts85, but not wild-type murine cells, was markedly inhibited following incubation at a nonpermissive temperature. In contrast, the nonpermissive temperature did not affect class I presentation of a minimal OVA peptide expressed in the cytosol. Therefore, these results provide a second example in which a temperature sensitive mutation in the ubiquitin conjugation pathway inhibits MHC class I presentation of native OVA. Surprisingly, incubation at the nonpermissive temperature did not inhibit class I presentation of chemically denatured and alkylated OVA microinjected into the cytosol of mutant cells. Similarly, the presentation of endogenously synthesized OVA (which is expressed from a recombinant vaccinia virus and, presumably, is misfolded in the cytosol) was also not inhibited in both mutant cell lines. Methylation of the lysine groups in denatured OVA, which blocks ubiquitin conjugation, reduced but did not eliminate the presentation of denatured OVA, providing evidence for both ubiquitin-dependent and ubiquitin-independent pathways for class I presentation. In contrast, a proteasome inhibitor blocked class I presentation of all forms of OVA, while a control peptide aldehyde was not inhibitory. These results indicate that modification of the structure of a protein can influence its requirements for ubiquitin conjugation for efficient class I presentation, with the key alteration possibly being the loss of proper conformation. However, regardless of the form of the Ag, the proteasome appears to be required for generating peptides from both endogenously synthesized and microinjected OVA for class I presentation.     

Alar fold resection in horses: 24 cases (1979-1992)

Between 1979 and 1992, the alar folds were resected bilaterally in 22 horses and unilaterally in 2 horses. Abnormal respiratory tract noise and exercise intolerance were the primary complaints prior to surgery. Significantly (P = 0.01) more Standardbreds underwent resection of the alar folds, compared with the number of Standardbreds in the hospital population during the same period. The alar folds palpated abnormally thick in 13 horses and normal in 11 horses. Temporary dilatation of the nares with mattress sutures or clips lessened the respiratory tract noise and improved exercise tolerance in all 8 horses in which the diagnostic test was performed. Manual elevation of the alar folds reduced respiratory noise in the 11 horses evaluated. Long-term follow-up evaluation by telephone was available for 14 horses. All surgical incisions had healed cosmetically. Respiratory tract noise was decreased, and exercise tolerance improved in 10 of 14 (71%) horses. Complete charted racing information was obtained for 16 horses. Fourteen horses started their first race a mean of 118 days (range, 13 to 321 days) after surgery. The mean number of starts after surgery was 51, with 14 of 16 (88%) horses starting more than 6 times after surgery. Of the 16 horses, 8 horses raced at least 3 times before and after surgery; 4 had improved racing performance, 2 had similar performance, and 2 had decreased performance. Five Standardbreds never raced, and 1 Standardbred raced once before surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

The lives of female physicians

Survey data from 113 female physicians, 634 male physicians, and 41 female dentists were compared. Instruments designed to assess work satisfaction, work stress, marital satisfaction, family competence, and psychiatric symptoms and treatment were used, thereby exploring important life domains concurrently. The results suggest that female physicians are much more like both male physicians and female dentists than anticipated. Generally, female physicians describe high levels of work satisfaction, moderate levels of work stress, average-to-high levels of marital satisfaction, and relatively low levels of psychiatric distress. Their lower levels of practice income remain something of an enigma as gender remains the most powerful predictor of income and is not replaced in statistical analyses by specialty, hours worked, or other significant variables. Finally, female physicians who find higher levels of satisfaction in work also report higher levels of marital satisfaction and fewer psychiatric symptoms. For these women, a highly satisfying medical career does not apparently need to be experienced at the cost of marital or personal distress.     

Efficiency of computed tomography in diagnosis of silicotuberculosis

Seventy-five newborns from multiple pregnancies with very low and extremely low birth weight are studied. 94% of the infants under 1000 g and 66% of those above 1000 g are born by vaginal way. Intrapartal asphyxia develop most often the second twins with birth weight under 1000 g--64.7%. These are the infants with higher morbidity: RDS--56.5%, IVH--100%. The survival rate of the twins of this group is notably lower than that of the infants from singleton pregnancies with equal weight and gestational age: 12.1% under 1000 g and 69% above 1000 g, against 38.3% and 77.9% respectively.