Polyarthritis in MRL-lpr/lpr mice: mouse type II collagen is antigenic but not arthritogenic.

In addition to a lupus-like syndrome and massive T cell proliferation, MRL-lpr/lpr(MRL/l) mice develop an arthritic process very similar serologically and histologically to human rheumatoid arthritis (RA). Recently, we have developed in DBA/1 mice an experimental model of autoimmune arthritis (EAA) which shares clinical features with RA, by injecting homologous type II collagen (CII). In order to investigate the possible relationship between the spontaneous polyarthritis of MRL/l mice and collagen induced EAA, we immunized MRL/l mice with mouse (M) CII. Our findings revealed that the injection of 100 micrograms M-CII in young or old MRL/l mice did not modify the articular pathology which spontaneously develops in non-injected mice. Circulating autoantibodies to native M-CII were found in the sera of immunized young mice but were not detected in non injected or immunized old mice. Conversely, denatured alpha 1 (II) chains or CB peptides derived from M-CII were recognized by most of the MRL/l sera whether mice had been immunized or not. The incidence of positive sera as well as the intensity of the response evaluated by Western blot analysis increased with the age of the mice. Taken together, our data suggest that, even if the injection of homologous CII in MRL/l mice may accelerate the onset of joint pathology, the spontaneous disease arises independently of an autoimmune response against native CII.

Histological patterns of bone and articular tissues after orthopaedic reconstructive surgery (artificial joint implants).

Revision surgery after failures of joint replacements leads to histological studies on joint and bone tissues close to the implanted material. Aspectic loosening is the main complication. The surgical pathologist has to identify wear debris (metal, polyethylene, polymethylmethacrylate, chiefly) which promotes a histiocytic granuloma. Some surgical procedures such as cup or resurfacing arthroplasties create a new articular surface and a bone remodeling or necrosis. Cemented joint prostheses show various membrane structures between bone and the cement mantle while there is an association of bone resorption and formation. Non-cemented, porous-coated joint prostheses induce little bone ingrowth, even in satisfactory clinical results. Mechanical factors are predominant in massive limb prostheses. For silicone elastomer implants or artificial ligaments, wear of material promotes many tissular reactions. Often used bone grafts show little creeping substitution process in case of homografts, even well-incorporated on X-rays. More retrieval specimen studies are necessary to delineate precise topographical histological lesions, including non-loosened joint implants.

PP60c-src expression in osteoclasts from osteopetrotic children and in giant tumor cells.

Malignant infantile osteopetrosis is a severe congenital disease characterized by impaired osteoclast activity. Among the multiple factors that influence bone resorption, the c-src protooncogene product pp60c-src plays an essential role, since mice which lack pp60c-src develop osteopetrosis. To gain insight into the possible role of pp60c-csrc in the pathogenesis of infantile osteopetrosis, we examined the osteoclasts of three children displaying the typical features of the disease, aged respectively one, four and seven months. pp60c-csrc expression and localization, together with the expression of a 80/85-kilodalton pp60c-src substrate, cortactin, were examined by immunoelectron microscopy. Osteoclasts from two giant cell tumors were used as controls. Bone and tumor samples were fixed in 4% paraformaldehyde, included in LR-White resin at -30 degrees C and the sections processed with mAb 327 or mAb anti p80/85 by an immunogold technique. pp60c-src was expressed in the cytoplasm, in nuclear membranes and in nuclei of the osteoclasts of the three osteopetrotic children. The subcellular localization of the kinase was not different from the localization in giant tumor cells. In both cases cortactin was abundant. In conclusion, in three children with malignant osteopetrosis, pp60c-src expression in osteoclasts does not appear to be involved in the pathogenesis of the disease. The presence of this protein, however, does not necessarily reflect normal c-src tyrosine kinase activity, nor normal c-src-dependent intracellular signaling pathways. Moreover the presence of the protein in nuclear membranes, and especially around nuclear pores supports the hypothesis that in osteoclasts, c-src may participate in the regulation of RNA processing.

[Double mitral orifice. An anatomical case]. / Orifice mitral double. Une observation anatomique.

A double mitral orifice was discovered at autopsy in a 74 year old woman. Death resulted after several episodes of cardiac failure complicating mixed mitral and aortic valve disease. A vertical limbus bridged the mitral annulus separating it into two distinct right and left orifices, with oblique long axes aligned towards the lower part of the limbus perpendicular to each other from the left atrial view. After opening the left ventricle, both orifices were observed to have their own sets of chordae tendinae attached to normal papillary muscles: the right orifice to the posterior and the left to the anterior papillary muscle. The inferior end of the limbus was attached to a supplementary papillary muscle. Echocardiography and CT scanning were performed before dissection. This malformation results from symphysis of the mid parts of the two mitral leaflets during embryonic stages 15 and 16 (8-10 mm vertex-coccyx, 31st-33rd days).

[An experimental study of bioglass implants in bone]. / Les bioverres et le tissu osseux: Etude expérimentale.

The tolerance and response of bone to bioglass have been studied using implants of various chemical constitution in animals.Glass discs were inserted between the inner and outer tables of the skull in 32 rabbits and small glass stick were implanted in the medullary cavity of long bones in 6 dogs. The results were analysed between 6 and 18 months later. High resolution radiographs and histopathological examination were performed.Some glass behaves like an inert material but other specimens are biodegradable and induce a satisfactory bone response in adjacent bone. Any new bone formation does not follow the classical stages of connective tissue, cartilage and woven bone. Bioglass is more suitable for bone than many other materials now in use and further applications in orthopaedic surgery may be considered.

[Hip surgery: local tissue reactions]. / La hanche opérée: réactions tissulaires locales.

Present extent of total hip prostheses, protracted course of first operations lead to pathological studies on local tissue reactions, sign of the failure or of the damaging of the artificial hip. Another pathology, often as intricate, is observed after more conservative surgery: high femoral osteotomies, cup arthroplasties, femoral metallic prostheses. Failure of an high femoral osteotomy shows a running of osteoarthritic lesions the topography of which is always modified by the new orientation of the articular bearing segment. Osteosclerosis, osteoarthritic cysts may develop on a preexisting osteophytosis. Osteonecrosis or bone resorption are sometimes found. Anatomical results in case of a successful osteotomy are scarce. Fibrous layer eventually quoted as a guide to the development of fibrocartilage is more often associated with osteoclast mediated bone loss. Efficient bone remodelling is assumed only, today, by radiological proof. Failures of cup arthroplasties induce femoral bone or acetabular cartilage lesions which are different according to the surgical technic. Some are marked by cartilage destruction of the acetabula or by a cup dislodgement. Bone structure in those cases shows under the cup a good remodelling with a fibrous or fibrocartilaginous mantle originating from the bone marrow spaces and the capsular attachment. In other cases, the femoral head presents areas of superficial or total osteonecrosis, signs of intense osteoclastic activity, cleaving of the fibrous surface and eventually metallic debris or cement induced histiocytic granuloma. A fibrous layer may develop between the cup and the acetabula. Femoral metallic prostheses may damage in some years cartilage of the acetabula. Osteoarthritic bone remodelling is sometimes observed in close contact with the metallic collar. Lesions of capsular tissues are eventually represented by metallic debris or an histiocytic granuloma due to cement anchorage. Material received at the time of surgical revision on total hip arthroplasties concerns chiefly the newly formed capsular and synovial tissues. Their appearance is quite similar to the tissular layers found between prosthetic material and bone or cement. For the pathologist, main inquiries are the rule out of an infection, the extent and course of the macrophage or giant cell response, the nature of wear debris or of the products of corrosion and the histological factors contributing to the loosening of the prosthetic components. It should be stressed that any physiopathological schedule of an artificial hip failure is a topographical and dynamic problem only partly resolved by studying autopsy material.

[A case of hyalinizing spindle cell tumor with giant rosettes in the presacral region. Immunohistochemical and ultrastructural study]. / Un cas de tumeur à cellules fusiformes hyalinisante avec rosettes géantes de la région présacrée. Etude immunohistochimique et ultrastructurale.

Hyalinizing spindle cell tumor with giant rosettes is a slowly growing tumor with a risk of local recurrence in case of incomplete surgical excision that could be regarded as a distinctive type of low-grade fibroblastic tumor. We report a case involving the presacral area. This tumor was composed of areas of bland spindle cell proliferation with a fascicular pattern in a fibrous or myxoid stroma, intermixed with giant rosettes consisting of rounded cells surrounding a central collagen core. The tumor expressed vimentin, and, for cells comprising the rosettes, S-100 protein, NSE and CD-57. These latter cells exhibited ultrastructural features of Schwann cells, the tumoral cells of fascicular area exhibiting features of fibroblastic cells. Flow cytometry showed DNA-aneuploidy and a very low S-phase fraction. This tumor appeared to be composed of two cellular components, fibroblastic and Schwann cells, located, at the opposite of neurofibroma, in two distinct areas.

[Arthritis of the wrist disclosing osteoid osteoma of the capitate bone]. / Arthrite du poignet révélatrice d'un ostéome ostéoïde du grand os.

A 22-year-old woman with an osteoid osteoma of capitate bone presented initially with arthritis of wrist. Bone scan imaging and digital subtraction angiography allowed diagnosis of a nidus. This case draws attention to articular manifestations of osteoid osteoma.

[Desmoid fibroma of the abdominal wall. Apropos of a case]. / Fibrome desmoïde de la paroi abdominale. A propos d'un cas.

A case of desmoid fibroma of anterior abdominal wall, an exceptional benign tumor, is reported. Based on results of CT scan imaging of this lesion, differential diagnosis of other expansive processes of abdominal wall are discussed. This benign tumor is a potentially serious lesion due to its infiltrating character and the high incidence of recurrence. The need for total surgical excision is emphasized.

[Fibrosarcoma of bone]. / Fibrosarcomes des os.

The authors have treated forty-five cases of fibrosarcoma of bone between 1949 and 1979. Tumours with chondrogenesis or osteogenesis to any extent have been excluded from the study. The conclusions are that fibrosarcoma represent 10 p. 100 of all bone tumours. Microscopy was difficult and in some cases it was not easy to determine both the fibroblastic origin and the presence of malignancy. Eight per cent of the tumours were primary and 20 p. 100 secondary. The global results indicated 40 p. 100 survival after five years. Twenty-four cases were treated by amputation of which twenty-two were followed up and fifteen were alive after five years. In nine cases, resection was performed. Recurrence occurred in five cases, three of which had to be amputated of which two survived. Two others were treated by irradiation without success. Ten cases were treated primarily by irradiation of which only three survived after heavy dosage. Proximally situated tumours had a very poor prognosis with no survival. The prognosis appeared to be better in those under forty years of age (55 p. 100 survival) than over forty years (11 p. 100 survival).

[Bone metastasis simulating a chondrosarcoma (author's transl)]. / Métastases osseuses simulant un chondrosarcome: à propos de 3 cas.

The authors report three cases of bone tumours, two in the scapula and one in the pelvis, which simulated chondrosarcoma on radiological examination. After biopsy it was concluded that they were metastases secondary to carcinoma of the bladder in one case and of unknown origin in the other two.

[Acute chondrolysis following slipped capital femoral epiphysis. A study of 41 cases (author's transl)]. / La chondrolyse ou coxite laminaire juvénile après épiphysiolyse fémorale supérieure. Etude clinique et thérapeutique à propos de 41 observations.

The authors have seen 41 instances of chondrolysis following slipped capital femoral epiphyses. Most of the cases were followed-up for more than five years. The main clinical features are reviewed. There is joint stiffness and generalised narrowing of the joint space during the year following the initial lesion. The evolution of the lesion is unpredictable. A number of possible radiological changes may develop including renewal of the joint space, modifications in the femoral head with a tendency towards protrusio, and osteophyte formation at the lateral margins of the acetabulum. In five cases a biopsy was performed which showed a non-specific dystrophy of the acetabular and femoral cartilage, with sub-chondral bony change different from that found in epiphyseal necrosis. The synovium did not show inflammatory change. The treatment should not be surgical at an early stage but the effectiveness of traction was uncertain. Later, corrective osteotomies may be indicated. Definitive surgical procedures such as arthrodesis or arthroplasty should not be made early because late clinical recovery has been noted. Cup arthroplasties gave deceptive results. The etiology of this disease is discussed.

[Giants schwannoma of the sacrum. Apropos of 3 cases and review of the literature]. / Schwannomes géants du sacrum. A propos de 3 cas et revue de la littérature.

Giant sacral schwannoma is a very rare tumor (25 cases reported). The authors report 3 cases of giant sacral schwannoma treated by curettage through posterior approach and discuss symptoms and treatment. These tumors were characterized by their minimal symptoms compared to radiographic findings. Magnetic resonance imaging must be performed in order to detect extraosseous tissue component and intradural invasion. A biopsy was performed to confirm the diagnosis before definitive treatment. Wide resection was proposed by many authors because of the high recurrence rate. We believe that a wide resection is too sever as it causes neurologic sacrifices. A curettage through posterior approach preserves nerve function, and if a local recurrence occurs it remains possible to perform a wide resection. When sacroiliac joint instability is detected, a lumboiliac arthrodesis is indicated. Osteosynthesis could be performed with spine device (using pedicular and iliac screws).

[Tumour-like bone manifestations in Hodgkin's disease. A report of two cases (author's transl)]. / Localisations osseuses d'allure tumorale de la maladie de Hodgkin. A propos de 2 cas simulant une tumeur primitive.

Two cases are reported in which the diagnosis of Hodgkin's Disease was revealed after a bone biopsy of an apparently primary lesion. In fact, the disease was already generalised and the authors question the existence of purely osseous varieties of the disease. Of the two reported cases, one died rapidly and the other had a long-term remission.

[Primary leiomyosarcoma of bone. Report of 5 anatomo-clinical cases and review of the literature]. / Léiomyosarcome primitif osseux. Présentation de cinq observations anatomo-cliniques et revue de la littérature.

INTRODUCTION: Leiomyosarcoma is a malignant smooth muscle tumor occurring most frequently in uterus or soft tissues and more rarely in bone. MATERIALS AND METHODS: We report the clinicopathologic, immunohistochemical and ultrastructural findings of five cases of primary leiomyosarcoma of bone treated in our Department between 1991 and 1994. The pertinent medical literature is discussed. RESULTS: The tumors were located respectively in the distal tibia (n=2), the distal femur, the sternum and the ilium (n=1). Four lesions were high-grade and one low-grade. All patients (3 women and 2 men) underwent wide surgical resection associated with polychemotherapy in four cases. Two patients died of metastatic disease, two had local recurrence and one is alive with no evidence of disease at the last follow-up. DISCUSSION: Excluding cases which involve the facial skeleton, there are to our knowledge 95 cases of primary leiomyosarcoma of bone reported in the literature. This tumor arises more commonly in adults (mean age: 49 years) with an equal gender distribution and involves predominantly the long bones near the knee. In the majority of cases, plain X-rays exhibit an osteolytic lesion with cortical penetration and indistinct margins. The diagnosis is based on microscopic features demonstrating fusiform tumor cells arranged in interwoven bundles, and the immunohistochemical results of widespread cytoplasmic positivity for smooth muscle actin. The best pronostic parameter is the histologic grade correlated with both the recurrence and metastatic rates as well as the survival rate. Surgery constitutes the main treatment since chemotherapy or radiotherapy did not provide an improved prognosis over a wide resection.

[Palmar localization of epithelioid sarcoma mimicking Dupuytren's disease]. / Localisation palmaire d'un sarcome épithélioïde simulant une maladie de Dupuytren.

A case of epithelioid sarcoma localized in the palm of the left hand in a 32-year-old woman is reported. The tumor evolved for many years, clinically and microscopically simulating palmar fibromatosis. Epithelioid sarcoma is an uncommon malignant tumor, often misdiagnosed by surgeons and pathologists. It occurs in young patients and is often localized at the upper distal extremity. Microscopically, epithelioid sarcoma shows nodules manifesting fibrous hyaline cores with central necrosis. It contains epithelioid and spindle cells immunoreactive to keratin, epithelial membrane antigen and vimentin. Recurrences, lymph node metastases and lung metastases are frequent. Surgical literature tends to recommend wide "en bloc" excision or amputation, combined or not with adjuvant radiation therapy.

Isolation of superoxide dismutase mutants in Escherichia coli: is superoxide dismutase necessary for aerobic life?

Mu transposons carrying the chloramphenicol resistance marker have been inserted into the cloned Escherichia coli genes sodA and sodB coding for manganese superoxide dismutase (MnSOD) and iron superoxide dismutase (FeSOD) respectively, creating mutations and gene fusions. The mutated sodA or sodB genes were introduced into the bacterial chromosome by allelic exchange. The resulting mutants were shown to lack the corresponding SOD by activity measurements and immunoblot analysis. Aerobically, in rich medium, the absence of FeSOD or MnSOD had no major effect on growth or sensitivity to the superoxide generator, paraquat. In minimal medium aerobic growth was not affected, but the sensitivity to paraquat was increased, especially in the sodA mutant. A sodA sodB double mutant completely devoid of SOD was also obtained. It was able to grow aerobically in rich medium, its catalase level was unaffected and it was highly sensitive to paraquat and hydrogen peroxide; the double mutant was unable to grow aerobically on minimal glucose medium. Growth could be restored by removing oxygen, by providing an SOD-overproducing plasmid or by supplementing the medium with the 20 amino acids. It is concluded that the total absence of SOD in E. coli creates a conditional sensitivity to oxygen.

rpoB sequence analysis of cultured Tropheryma whippelii.

Until recently no isolate of Tropheryma whippelii was available, and therefore genetic studies were limited to those based on PCR amplification of conserved genes. In this study we determined the nucleotide sequence of rpoB (encoding the beta-subunit of RNA polymerase) from a cultured strain of T. whippelii using degenerate consensus PCR and genome walking. The T. whippelii rpoB consists of 3,657 bp with a 50.4% GC content and encodes 1,218 amino acids with a calculated molecular mass of 138 kDa. Comparison of T. whippelii RpoB with other eubacterial RpoB proteins indicated sequence similarity ranging from 57.19 (Mycoplasma pneumoniae) to 74.63% (Mycobacterium tuberculosis). Phylogenetic analysis of T. whippelii based on comparison of its RpoB sequence with sequences available for other bacteria was consistent with that previously derived from the 16S ribosomal DNA (rDNA) sequence, indicating that it belongs to the actinomyces clade. The sequence comparison allowed the design of a primer pair, TwrpoB.F and TwrpoB.R, specific for T. whippelii rpoB. When incorporated into a PCR, this primer pair allowed the detection of T. whippelii rpoB in three of three 16S rDNA PCR-positive biopsy specimens and zero of seven negative controls. rpoB could therefore be targeted in PCR-mediated detection and identification of this emerging bacterial species. This approach has previously been shown useful for the identification of related mycobacteria. This study underscores that a method involving isolation and then propagation of emerging bacteria is a useful way to quickly achieve extensive molecular knowledge of these pathogens.