Mechanical stimulations on human bone marrow mesenchymal stem cells enhance cells differentiation in a three‐dimensional layered scaffold

Scaffolds laden with stem cells are a promising approach for articular cartilage repair. Investigations have shown that implantation of artificial matrices, growth factors or chondrocytes can stimulate cartilage formation, but no existing strategies apply mechanical stimulation on stratified scaffolds to mimic the cartilage environment. The purpose of this study was to adapt a spraying method for stratified cartilage engineering and to stimulate the biosubstitute. Human mesenchymal stem cells from bone marrow were seeded in an alginate (Alg)/hyaluronic acid (HA) or Alg/hydroxyapatite (Hap) gel to direct cartilage and hypertrophic cartilage/subchondral bone differentiation, respectively, in different layers within a single scaffold. Homogeneous or composite stratified scaffolds were cultured for 28 days and cell viability and differentiation were assessed. The heterogeneous scaffold was stimulated daily. The mechanical behaviour of the stratified scaffolds were investigated by plane–strain compression tests. Results showed that the spraying process did not affect cell viability. Moreover, cell differentiation driven by the microenvironment was increased with loading: in the layer with Alg/HA, a specific extracellular matrix of cartilage, composed of glycosaminoglycans and type II collagen was observed, and in the Alg/Hap layer more collagen X was detected. Hap seemed to drive cells to a hypertrophic chondrocytic phenotype and increased mechanical resistance of the scaffold. In conclusion, mechanical stimulations will allow for the production of a stratified biosubstitute, laden with human mesenchymal stem cells from bone marrow, which is capable in vivo to mimic all depths of chondral defects, thanks to an efficient combination of stem cells, biomaterial compositions and mechanical loading.     

Monoclonal antibody mapping of the antigenic surface of human thyrotropin and its subunits

Although the amino acid sequence of the alpha- and beta-subunits of glycoprotein hormones in various species has been deciphered, data on their tertiary structure are not abundant. This impedes correlation between structure and function. The availability of monoclonal antibodies to human TSH (hTSH) offers the opportunity to enumerate the antigenic determinants present on the surface of hTSH and its subunits and to examine their spatial relationships. Twenty-eight monoclonal antibodies to hTSH were obtained from several fusions, and screens carried out separately in the laboratories involved in this study. Affinities for hTSH ranged from 10(8)-10(11) M-1. Cross-reactivity with bovine TSH (bTSH), human gonadotropins (hLH, hFSH, and hCG), and the alpha- and beta-subunits of hTSH distinguished 10 groups of monoclonal antibodies (mAb) according to their main cross-reactions: 1) hTSH alpha, hLH, hFSH, and hCG; 2) hTSH alpha, bTSH, hLH, hFSH, and hCG; 3) hFSH; 4) bTSH and hFSH; 5) bTSH, hLH, and hFSH; 6) bTSH, hLH, hFSH, and hCG; 7) hTSH beta; 8) hTSH beta and bTSH; 9) hTSH beta and hFSH; and 10) hTSH beta, hLH, hFSH, and hCG. mAb were incorporated into 2-site binding assays to probe hTSH by a 28 X 28 matrix, the free alpha-subunit by a 4 X 4 matrix, and the free beta-subunit by a 18 X 18 matrix. Regarding intact hTSH, 12 different clusters of mAb were distinguished and interpreted as reflecting 12 distinct antigenic regions on the surface of the hTSH molecule. Two of them were localized on the alpha-subunit, and 6 on the beta-subunit; 4 were only expressed by the holo-hormone and, thus were designated conformational antigenic regions (alpha beta). Surface mapping of the free alpha- and beta-subunits was virtually identical to that observed with the holo-hormone. Modification of the operative conditions of mAb reacting only with holo-hTSH shows that they recognize the alpha-subunit, but not the beta-subunit of hTSH. These results indicate that 1) hTSH beta presents epitopes that are evolutionary conserved; 2) hTSH alpha presents several epitopes that are species specific and 2 that are not hormone specific; 3) dissociation of hTSH does not modify the antigenic surface expressed by both subunits when they are associated; and 4) some of the conformational determinants expressed only by holo-hTSH are more likely derived from the alpha-subunit than from the beta-subunit.     

Isolated pseudo-tumoral tuberculosis of the spleen. A case report

INTRODUCTION: The tuberculosis isolated tumoral spleen is rare, even in the countries to strong tubercular endemic. EXEGESIS: From an observation, concerning an important, tumoral and isolated splenomegaly in 48-year-old-man. The authors put the accent on his tumorous variety by the clinic, the imagery and on macroscopic appearance of the operative piece. Are discussed the isolated character, the way of dissemination, the site of initial infestation and the deceitful character of haematological manifestations. A splenectomy to diagnostic and therapeutic goal have been realised, associated to the chemotherapy. CONCLUSION: This is an expression of the profound organ's tuberculosis rich on endothelial reticular system. It's mean a singular topography of the bacillary lesion and a great distribution of the tubercular affect.     

Distomatose biliaire pseudotumorale diagnostiquée au cours d’une sphinctérotomie endoscopique

The hepatobiliary fascioliasis is a parasitical disease caused by Fasciola hepatica. The diagnosis is often made in the phase with symptoms of biliary obstruction or acute pancreatitis. We report a case of pseudotumoral hepatobiliary fascioliasis diagnosed with the discovery of hemobilia and extraction of parasitic flukes during endoscopic biliary sphincterotomy. Retrograde cholangiopancreatography with endoscopic sphincterotomy confirmed the diagnosis and enabled treating fascioliasis by removing the biliary obstruction by removal of parasites.     

Le pilomatricome malin cervical métastatique : à propos d’un cas

We report the case of a 66-year-old patient with a pilomatrix carcinoma from the right submandibular region with pulmonary and cerebral metastases. The histological confirmation of the diagnosis has been based on the biopsy of the submandibular tumefaction which was rapidly growing. We tried at first a doxorubicine and cisplatine chemotherapy because of the considerable locoregional extension and the existence of pulmonary metastases. The patient response to three cures of chemotherapy was spectacular with a partial clinical response (75%) and a partially cleaned-up chest observed in the radiological evaluation. In the 5th cycle of chemotherapy following the same protocol, the patient presented a relapse with cerebral metastases. The patient received hypofractionated radiotherapy on the brain followed by etoposide and cisplatine chemotherapy, then oral vinorelbine. The patient died of progressive disease after 32 weeks.     

Immunoradiometric analysis of circulating human glycosylated and nonglycosylated prolactin forms: spontaneous and stimulated secretions.

The monoclonal antibodies (MAbs) obtained in mice immunized with human PRL coupled to an anti-PRL MAb were screened for their ability to distinguish the glycosylated (G-) and nonglycosylated (NG-) forms of PRL. The 431-29 MAb exhibited high affinity binding for NG-PRL but little or no cross-reactivity to G-PRL. Using this antibody in conjunction with other MAbs which equally recognized both forms, we developed 2 immunoradiometric assays which were used to determine the amount of G- and NG-PRL in plasma. In 85 normal subjects, NG-PRL baseline levels averaged 6.6 +/- 3 micrograms/L, and represented 76 +/- 8% of the total PRL immunoreactivity. In 74 pregnant women, this proportion was significantly higher during the last 2 trimesters (84 +/- 4% and 85 +/- 6%), as compared to the first trimester (76 +/- 7%). In 6 healthy volunteers studied over 24 h, 79% of the NG-PRL peaks detected using the cluster algorithm occurred concomitantly to a G-PRL peak. The mean NG-PRL/PRL ratio was significantly higher during NG-PRL pulses (81 +/- 9%) than during valleys (71 +/- 12%). Similarly, this ratio was significantly increased during TRH or metoclopramide stimulated PRL secretion (to 88 +/- 7% and 86 +/- 6%, respectively). We conclude that 1) NG-PRL is the predominant immunoassayable form of PRL in plasma; 2) both G- and NG-PRL are cosecreted but NG-PRL is the main PRL form released during spontaneous or pharmacologically induced PRL secretion.     

Symptomatic periodic paralysis secondary to primary Sjogren's syndrome

INTRODUCTION: Hypokalaemic periodic paralysis can be primitive or secondary to potassium deficiency which can arise from several causes. Primary Sjogren's syndrome is a rare cause related to kidney involvement. CASE REPORT: A 50-year-old woman has been admitted for hypotonic tetraparesis which had appeared a few days earlier. History taking revealed three previous similar episodes with a notion of oral and lacrimal dryness. Laboratory tests revealed severe hypokalaemia, hyperchloremia, alkaline urinary pH and a minima 24h proteinuria. Additional investigations led to the diagnosis of a primary Sjogren's syndrome defined on the basis of international criteria. Kidney biopsy revealed tubular-interstitial nephritis. Oral corticostero?d therapy and potassium supplementation led to symptom improvement. A recurrent episode also responded to treatment. Additional urinary alkalinisation has prevented further relapse. DISCUSSION: Primary Sjogren's syndrome is an exocrine disease causing systemic disorders. Tubular-interstitial nephropathy may occur in 25 percent of patients leading to distal tubular acidosis defined by the association of hypokalaemia, hyperchloremia and alkaline urinary pH. When hypokalaemia is severe, periodic paralysis may occur. CONCLUSION: Primary Sjogren's syndrome can lead to nephropathy and subsequent hypokalaemic periodic paralysis. Urinary alkalinisation is essential to prevent this catastrophic presentation from recurring.