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Biomedical subjects

L Marcellin

Publications and source records attributed to L Marcellin.

At least 19 recordsLinked to original sources

The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans.

BACKGROUND: This study determined the histological features of the atrial myocardium connecting the coronary sinus and the left atrium in humans. METHODS AND RESULTS: Ten necropsied hearts were studied by performing serial longitudinal sections parallel to the long axis of the coronary sinus that extended its full length using a large microtome. In all specimens, the venous wall of the coronary sinus was surrounded by a cuff of striated muscle extending 40+/-8 mm from the ostium. Striated myocardial connections of varying number and morphology left this coronary muscle cuff and connected to the left atrium; they ranged from 1 to 2 fascicles to a widely intermingled continuum (thickness, 2.79+/-2 mm; width, 2.91+/-3.5 mm). These connections originated 8.8+/-5.7 mm from the coronary sinus ostium and inserted 18+/-11 mm distally into the left atrium. The insulating compartment in which the connections traversed between the left atrium and the coronary sinus was mostly formed of adipose tissue. The valve of Vieussens was found in 6 hearts at a mean distance of 3.4+/-3.2 mm from the distal extremity of the coronary sinus muscle cuff. CONCLUSIONS: In the human heart, a consistent but morphologically variable left atrial coronary sinus myocardial connection was found. This emphasizes the need for surgical dissection or catheter ablation in or around the coronary sinus to eliminate these connections.

Adult↗

Nodular glomerulosclerosis with deposition of monoclonal immunoglobulin heavy chains lacking C(H)1.

The objective of this study was to further characterize the clinical and immunopathologic features of heavy chain deposition disease (HCDD), a recently described entity. Four patients were diagnosed as having HCDD on a kidney biopsy. All presented with nodular glomerulosclerosis with deposition of gamma1 heavy chains lacking CH1 epitopes, but without light chains. Two different patterns were observed in the serum. First, patients 1 and 2 had a circulating monoclonal IgGlambda containing a short gamma1 heavy chain lacking CH1 epitopes, with an apparent molecular weight of 40 kD consistent with a complete CH1 deletion. Biosynthetic experiments also showed that the deleted heavy chain was produced in excess compared with light chains, and was secreted in vitro together with half Ig molecules, although these abnormal components were not detected by Western blot analysis of whole serum. Second, patients 3 and 4 had a circulating monoclonal IgG1lambda with an apparently normal, nondeleted heavy chain subunit, but serum fractionation followed by immunoblotting revealed an isolated monoclonal gamma1 chain lacking CH1 epitopes. These data strongly suggest that renal deposition of a CH1-deleted heavy chain circulating in low amounts in the serum as a free unassembled subunit is a major feature of HCDD. The CH1 deletion is most likely responsible for the premature secretion in blood of the heavy chain by a clone of plasma cells.

Adult↗

[A case of a aggressive giant-cell tumor with multiple bone metastases].

PURPOSE OF THE STUDY: Giant-cell tumor are known for local recurrence. Metastases are rare (2 p. 100), and generally located in the lung. We present a case with multiple bone metastases and rapid course. MATERIAL, METHODS AND RESULTS: A 45-year-old man presented a 5 cm giant-cell tumor of his right distal tibia and two other localisation in the fifth and sixth cervical vertebral bodies. He underwent a resection of the distal tibia and reconstruction with a controlateral free vascularized fibula. The bodies of the fifth and sixth cervical vertebral were resected and replaced by an iliac crest graft. Other localisations appeared in iliac right crest, in the posterior wall of the cotyle and in the second, third and fourth cervical vertebral bodies. Chemotherapy was administered and clinical signs regressed but eight months later the patient presented a recurrence of his tumor in the distal tibia with new localisation in the left fifth rib, in the right clavicle, in the frontal bone, in right ischio-pubal branch and in the right proximal femur. A new chemotherapy was performed but had little effect and probably hasved dubic death 13 month after the first symptom. DISCUSSION: The present observation is characterised by the large number of localisations (13; the highest number found in the literature was 11 localisations) and by the rapidity of the clinical course. Low grade giant-cell tumors generally give benign metastase with a course lasting several years. The chemotherapy helpt us to slow the progression of the lesions but was unable to prevent the development of new localisation and the recurrence in the distal tibia. More over, its toxicity could have caused the death of the patient. CONCLUSION: We present the case of one patient who presented a giant-cell tumor with unusual presentation: multiple bony metastases with rapidly fatal outcome.

Antineoplastic Agents↗

Terminal deoxynucleotidyl transferase deficiency reduces the incidence of autoimmune nephritis in (New Zealand Black x New Zealand White)F1 mice.

Terminal deoxynucleotidyl transferase (TdT) enzyme activity in lymphocytes generates diversity in the Ag receptor repertoires by adding template-independent N nucleotides and disrupting homology-directed rearrangements. The importance of this diversity in vivo and the significance of the suppression of TdT during fetal life remain uncertain. Previous studies have shown that in TdT knockout mice (TdT(0)) 1) the T cell repertoire is less peptide oriented; and 2) natural autoantibody, particularly anti-DNA autoantibodies, are less polyreactive, and their mean affinities are reduced. Consequently, the suppression of TdT during early T/B cell ontogeny may participate in controlling autoimmunity. To study the impact of TdT suppression in autoimmune-prone mice, we introduced the TdT null mutation into the (NZB x NZW)F1 (B/W) mouse strain. We show that TdT deficiency significantly reduces the incidence of autoimmune nephritis and prolongs survival compared with those in control mice. Surprisingly, the long-term survivor TdT(0) mice produced amounts of anti-ADN and anti-histone autoantibodies similar to those of their TdT+ littermates. However, these TdT(0) mice showed no evidence of renal inflammation, and the immune deposits were restricted to the mesangium, whereas basal membrane deposits were clearly correlated with overt renal disease. The present study supports the idea that the absence of TdT enzyme activity in lymphocytes protects mice against autoimmunity and could offer a therapeutic approach to autoimmune diseases. Moreover, our results may help to unravel the mechanisms of lupus nephritis.

Animals↗

Loss of oral infectivity of tissue cysts of Toxoplasma gondii RH strain to outbred Swiss Webster mice.

We have developed a method for obtaining cysts of Toxoplasma gondii RH strain. Outbred Swiss Webster mice were infected subcutaneously (s.c.) or intraperitoneally (i.p) with 10(5) tachyzoites and given sulfadiazine 400 mg l-1 + NaHCO3 10 g l-1 in drinking water from day 1 to day 15 post-infection (p.i.). None of the mice infected i.p. survived, compared with 50% of the mice infected s.c. Cysts were detectable in the brain on day 45 p.i., and had ultrastructural features consistent with those of bradyzoites. However, these cysts were incapable of infecting mice via the oral route. In addition, immunofluorescence studies showed the persistence of P36 protein expression, indicating that the conversion to bradyzoites was incomplete.

Animals↗

[Muscular metastases disclosing adenocarcinoma].

The authors report the case of a 67-year old man, with no particular medical history, presenting a large swelling of the left thigh. Investigations conclude to metastases located in muscles of the left thigh and of the pelvis, secondary to an adenocarcinoma of presumed pancreatic origin. With reference to this case, features of muscular metastases are reviewed. Muscular metastases seldom occur during the course of a cancer and are exceptionally the first manifestation of a neoplastic process. They are usually described as a painful mass, but symptoms can be misleading and delay diagnosis. Images obtained by ultrasonography, tomodensitometry and magnetic resonance imaging are not specific and histological examination is necessary to confirm the diagnosis.

Adenocarcinoma↗

CD44 isoforms with exon v6 and metastasis of primary N0M0 breast carcinomas.

New isoforms of CD44 with alternatively spliced exons have recently been described. Expression of exon v6 seems to be of particular interest. It has indeed been associated with poorer outcome of breast cancer patients with node invasion at diagnosis. However, no data were available for patients N0M0 (with neither metastasis nor node invasion at diagnosis). Moreover, previous statistical analyses were realized using immunohistochemical methods to detect CD44v6 expression although several variants with exon v6 have been described. We investigated expression of isoforms containing CD44v6 using an RT-PCR approach and a panel of 25 normal breast specimens, 10 mammary fibroadenomas, 8 cystic samples and 52 primary breast tumors (38 invasive N0M0). Normal breasts, fibroadenomas, and cysts all express the same variant, A (with exon v6 only), while several transcripts are amplified in tumors. Expression of variants other than A correlates with acquisition of a malignant phenotype. Invasive cancers also express additional variants in comparison with in situ carcinomas. Metastasis capacities seem to be associated with transcription of variants other than A but also with no transcription of some of them, variants D (with exons v6 and v10) and L (with exons v6 to v10). Expression of variants D and L correlates with higher percentages of disease-free survival and better outcome. Expression of CD44 splice variants with exon v6, as detected by RT-PCR, might be a useful prognostic factor for breast cancer. However, since the series size is small, our results need to be confirmed by later studies on a larger number of patients.

Adult↗

Primary hepatic lymphoma associated with chronic hepatitis C.

Like other viruses (i.e Epstein'Barr virus), the role of hepatitis C virus is suspected in the pathogenesis of lymphoproliferative disorders. We report one case of primary hepatic malignant lymphoma associated with chronic hepatitis C viral infection. The diagnosis was obtained by percutaneous liver biopsy showing a non-Hodgkin's diffuse large cell lymphoma and micronodular cirrhosis. Serology for hepatitis C virus positivity was known three years before lymphoma diagnosis. Staging of the lymphoma confirmed multinodular primary hepatic lymphoma with no other detectable localisation. Complete remission has been obtained with aggressive chemotherapy. The role of hepatitis C virus in the pathogenesis of the lymphoma is unknown. An indirect mechanism is suspected. Chronic inflammation may evolve from polyclonal lymphocytic proliferation to true non-Hodgkin's lymphoma, as it has been suggested for non-Hodgkin's lymphoma in the emergence of cryoglobulinemia in hepatitis C positive patients.

Chronic Disease↗

CD44 exon 6 expression as a possible early prognostic factor in primary node negative breast carcinoma.

Breast cancer is the most common female malignancy affecting approximately one woman in eight. Many attempts have been made to define markers which may have potential clinical applications in diagnosis as well as therapy. New isoforms of CD44 with alternative spliced exons have recently been described. We studied the expression of CD44 exon 6 using a semi-quantitative RT-PCR reaction on a panel of 25 normal breast specimens, 10 mammary fibroadenomas, eight cystic samples and 52 primary breast tumors. Significant correlation was found between CD44 exon 6 expression and the overall survival of the N-M-population, P = 0.032, (logrank test by Mantel's method). The same result was also observed for the disease-free survival, P = 0.000002 (logrank test by Mantel's method). CD44 exon 6 expression, as detected by our RT-PCR-based method, might be a useful prognostic indicator of metastasis in breast cancer. However, these preliminary results need to be confirmed by later retrospective and prospective studies on a larger number of patients.

Adult↗

Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma.

PURPOSE: The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS: Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION: RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.

Adolescent↗

[High grade osteosarcoma of the lower limb. Complications and results of the treatment of 20 patients].

UNLABELLED: Over 11 years we treated 30 osteosarcomas: 20 of them were high grade non metastatic osteosarcomas of the lower limb, which were treated by neoadjuvant chemotherapy (Rosen T10, or OS 87 protocol of the French Society for Pediatric Oncology). MATERIAL AND METHODS: There were 12 males and 8 females; the mean age was 19 years (range 12-51). The site of the tumor was the femoral neck (1 case), femoral diaphysis (2 cases), distal femur (12 cases), proximal tibia (4 cases), distal tibia (1 case), 3 were IIA and 17 IIB according to Enneking system. Conservative treatment was performed in 17 cases: there were 12 knee prostheses, 4 allografts and 1 knee arthrodesis with allograft. RESULTS: a) Surgical complications: Mechanical complications occurred in 10 patients. The function was preserved 8 times. In 2 patients the knee became stiff. An infection occurred in 3 patients: a conservative treatment was possible in 2 of them with a fair result. In the third case, an above-the-knee amputation had to be done. b) Functional results were studied according to Enneking rating. 14 arthroplasties (12 done as first surgical treatment and 2 after mechanical complication) had a 68, 19 score. c) Oncologic results: 8 patients were good respondents and 12 patients were bad respondents to chemotherapy according to Huvos grading. One local relapse was observed which could be treated by mean of a second chemotherapy and a prosthetic reconstruction. The patient is still alive and disease-free at 7 years (9 years after the diagnosis of the osteosarcoma). 5 patients had distant metastasis (lung, bones, and brain). One out of 5 was good respondent and 4 out of 5 are presently dead. Using Kaplan Meier statistical analysis, the overall survival wzs 76.8 per cent and the event-free survival was 67.4 per cent at 80 months. CONCLUSION: We preferred a simple prosthetic reconstruction without osseous sleeve or an intercalary allograft if possible: these procedures allow the patient very rapid autonomy to have despite a prolonged chemotherapy.

Actuarial Analysis↗

E-cadherin mRNA expression in breast carcinomas correlates with overall and disease-free survival.

E-cadherin (Epithelial-cadherin) is a subclass of the cadherin family that plays a major role in the maintenance of intercellular junctions in epithelial tissues. E-cadherin is also involved in the interactions between epithelial cells and T lymphocytes. In order to explore the relationship between E-cadherin expression, cancer invasion and metastases in vivo, we estimated its expression in normal breast specimens, fibroadenomas, cystic samples and primary breast carcinomas using a semiquantitative reverse transcription-polymerase chain reaction. The relationship between E-cadherin expression, survival and disease-free survival was also investigated. In comparison with normal breasts, 70% of the primary tumors showed reduced expression of E-cadherin suggesting that downregulation of this cell adhesion molecule is a common event in breast carcinoma. Significant correlation was found between E-cadherin expression and the histological classification. Most of the advanced tumors grades (10/13 tumors with grade III) presented decreased E-cadherin expression. No correlation was found between E-cadherin expression, estrogen and progesteron receptors, age and menopausal status at diagnosis. However, disease-free and overall survival was associated with E-cadherin expression. Patients showing poorly expressed E-cadherin in tumor tissue had a worse prognosis. The same results were observed for women without lymph node invasion or metastasis at diagnosis even when they were grouped according to their histological grade for statistical analysis. Therefore, E-cadherin mRNA expression in invasive breast carcinomas might be an early prognostic factor of metastasis.

Adult↗

Protective effect of low doses of an anti-IL-4 monoclonal antibody in a murine model of acute toxoplasmosis.

Treatment with an anti-IL-4 monoclonal antibody protected susceptible C57BL/6 mice against challenge with an avirulent strain of T. gondii. Antibody therapy with 100 micrograms on days 0 and 7 post infection resulted in 100% survival of C57/BL6 mice infected orally. Survival was dose-dependent. Treatment prolonged parasitaemia but did not alter tissue parasite load. Increased serum IgG2a and IFN-gamma levels, together with low levels of IgG1, in mice treated with anti-IL-4 or an isotype control, indicated a trend towards a predominant Th1 response in all survivors. The persistence of an IgE response after treatment suggests that endogenous IL-4 was only partly neutralized or that other factors can induce the production of IgE in murine toxoplasmosis.

Acute Disease↗

[Lesions caused by techniques of endocavitary ablation using high frequency currents: anatomo-pathological aspects].

Anatomopathological studies have considerably increased our understanding of the ablative technique by radiofrequency current. They have provided information on the nature, extent and time dependency of the lesions induced. Despite variable results according to whether the experiments were performed in vitro or in vivo, a correlation has been observed between the volumes of the lesions and the energies used. One factor is unquestionable: monitoring the temperature allows better control of the lesion size than monitoring current intensity. However, other technical points are essential for this control such as ensuring good contact between the catheter and the endocardium and the definition of the optimal surface area of the electrode. Now that the conditions of efficacy and security of ablation by high frequency currents are known, anatomopathological studies in man have become rare. These studies, which will take a long time to perform due to the very nature of the technique and pathologies treated, should provide interesting anatomo-electrical comparisons to increase our understanding of certain arrhythmias.

Animals↗