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Biomedical subjects

L Laroche

Publications and source records attributed to L Laroche.

At least 145 records · Page 8Linked to original sources

Expression of V beta gene segments by Sezary cells.

The T-cell receptor V beta repertoire expressed by Sezary cells was determined in a series of 16 patients whose samples have been shown to contain a majority of tumor cells. By using anti-V beta monoclonal antibodies, polymerase chain reaction analysis of expressed V beta, and, in selected cases, nucleotide sequencing, we have shown that the expressed V beta segments belong to five V beta families (V beta 5, V beta 6, V beta 8, V beta 13, and V beta 18), which contain a large fraction of the T-cell receptor V beta repertoire and do not share significant similarities in complementary determining region 4. V beta segments from these five families were also found to be strongly expressed by CD4 + CD7- peripheral blood cells obtained by fluorescence-activated cell sorting from two healthy donors. The diversity of the V beta repertoire expressed by Sezary cells appears to be similar to that expressed by circulating non-neoplastic T cells. These data do not support the hypothesis that a common superantigen is involved in the initiation of this form of cutaneous T-cell lymphoma.

Antigens, CD↗

High-dose recombinant interleukin-2 in advanced cutaneous T-cell lymphoma.

BACKGROUND AND DESIGN: Treatment of cutaneous T-cell lymphoma is still a difficult challenge, once the usual therapies (topical chemotherapy, phototherapy, radiation therapy, and chemotherapy) have proved to be unsuccessful. New therapies, mostly immunotherapies, are currently under investigation. The use of recombinant interleukin-2 has already been evaluated in hematopoietic malignancies. We decided to treat patients with advanced cutaneous T-cell lymphoma relapsing or progressing in spite of the usual treatments with high-dose recombinant interleukin-2. Seven patients (three with mycosis fungoides, three with Sézary syndrome, and one with nonepidermotropic large-cell cutaneous lymphoma) were included in this open study. They were scheduled to receive recombinant interleukin-2 at a dose of 20 x 10(6) IU/m2 per day, administered by continuous infusion during three fortnightly induction cycles and five monthly consolidation cycles. RESULTS: Three complete responses (two responses to mycosis fungoides; one response to large-cell lymphoma) and two partial responses were obtained. The clinical response appeared after the first cycle of treatment in the good responders. The complete responses are still ongoing 33, 28, and 6 months after completion of recombinant interleukin-2 therapy and without any further treatment. Sequential immunophenotypic studies showed an increase of the CD1+ cells in the dermal infiltrates. No significant modification of natural killer or cytotoxic T cells could be seen. CONCLUSIONS: Despite our low number of cases, our results clearly show that some advanced cutaneous T-cell lymphomas can benefit from high-dose recombinant interleukin-2 therapy. Further studies are necessary to determine the exact place of recombinant interleukin-2 in the therapeutic arsenal of cutaneous T-cell lymphoma.

Adult↗

[Penetrating keratoplasty after graft preservation in organ culture at +37 degrees centigrade. 1-year results].

PURPOSE: To evaluate the clinical results of corneal transplantations using organ-cultured donor corneas. MATERIAL AND METHODS: We retrospectively studied our 50 first penetrating keratoplasties performed with corneas organ-cultured for 2 to 5 weeks at +31 degrees C (Inosol medium, Opsia). The average follow-up is 11.6 months. The main indications for grafting were bullous keratopathy (56%) and keratoconus (26%). RESULTS: At 1 year, the graft survival rate was 81%. The causes of graft failure were immune rejection (n = 3), non immune secondary endothelial decompensation (n = 3) and uncontrolled glaucoma (n = 1). The average endothelial density during the second year was 1,349 cell/mm2. It was 1,852 in the group of keratoconus and 751 in the group of bullous keratopathy. The average corrected visual acuity was 20/66 at 12 months. It was 20/45 in the group of keratoconus and 20/125 in the group of bullous keratopathy. The average astigmatism was 4.9 D, but running suture was still present at 12 months in most patients. Compared with graft survival after storage at +4 degrees C (retrospective paired control group), graft survival was higher after organ culture, but the difference does not reach the statistical significant threshold (p = 0.07). CONCLUSIONS: Organ culture is able to ensure the quality of corneal endothelium and then avoids non immune primary graft failure.

Aged↗

[Lymphoma with skin manifestations in HIV infection: 8 cases].

INTRODUCTION: Cutaneous lymphomas occurring in HIV infection are a rare disease. Most of them are high grade lymphomas with fulminant course and poor prognosis. OBJECTIVE: Evaluate clinical and histological aspects as well as immunophenotype and evolution of these lymphomas. PATIENTS AND METHODS: Eight patients with HIV infection were studied between 1992 and 1994. The clinical and histological features were reviewed by the members of the French Study Group for Cutaneous Lymphomas. Staging procedures for lymphomas were performed in 7/8 patients. RESULTS: Seven non epidermotropic lymphomas and one mycosis fungoides were reviewed. Patients were male (6 cases) and female (2 cases); their mean age was 45 years (27-63). The mean level of CD4 T cells/mm3 was 141 (20-380). Only one patient presented with extracutaneous lesions. These lesions were similar to seronegative patients, but unusual features were observed in two cases. Histological classification showed high grade lymphomas in 6/8 cases. The immunophenotype was: T-cell lymphoma in 4 cases, B-cell lymphoma in 3 cases; it could not be determinated in one case. Six patients died. The median of survival is 8 months in this series. DISCUSSION: Our series confirms the predominance of high grade lymphomas presenting in the skin. The T-cell phenotype is more frequent. The onset of a cutaneous lymphoma has a poor prognosis in HIV infection. Most of our patients had localised disease at presentation. Therapeutic management of these lymphomas must be codified.

Adult↗

Extracorporeal photochemotherapy: evaluation of two techniques and use in connective tissue disorders.

Extracorporeal photochemotherapy (ECP) consists of collection of mononuclear cells, their irradiation with UV-A light in the presence of a photoactivable molecule--8-methoxy-psoralen (8-MOP) being the most widely used--and their reinjection into a patient. Two technical approaches have been developed. The photopheresis procedure involves four steps: (i) 8-MOP is given to the patient orally, 2 h before collection of white blood cells; (ii) a discontinuous flow cell separator (UVAR, Therakos, West Chester, PA, U.S.A.) is used for cell collection. The final product (740 mL) has a hematocrit of 4.5 +/- 1.7%); (iii) irradiation, performed with the same UVAR apparatus, begins before all the cells are collected, and lasts for 180 min after collection; and (iv) after irradiation, the buffy-coat is reinjected into the patient. We developed a technique summarized as follows: (i) mononuclear cell collection is performed using the Spectra (Cobe, Denver, CO, U.S.A.) cell separator, which provides a highly enriched mononuclear cell concentrate (always > 90% purity), in a small volume < 150 mL, subsequently adjusted to 300 mL for irradiation. Hematocrit of the final product is always < 2%. (ii) Soluble 8-MOP is added to the mononuclear cell concentrate at a final concentration of 200 ng/mL. (iii) Mononuclear cell concentrate is transferred in an EVA plastic bag (Macopharma, Tourcoing, France) to ensure an efficient irradiation with a UV irradiator (Vilber Lourmat, Marne-la-Vallée, France). (iv) After irradiation at 2 J/cm2 (time < 20 min), the cells are reinfused into the patient. Experimental and clinical data suggest that ECP has potential applications in the treatment of connective tissue disorders, such as systemic sclerosis and rheumatoid arthritis. Although encouraging data have been obtained, further clinical trials are warranted to establish the role of this therapy in these indications.

Animals↗

Immunohistochemical and ultrastructural study of the cornea in Chandler's syndrome. Report of a case.

A corneal specimen obtained by surgery in a 55-year-old woman with Chandler's syndrome was studied by light and transmission electron microscopy as well as by immunocytochemistry. The pathologic features were abnormalities of the endothelially derived cells lining the posterior corneal surface with a fibrous material consisting of collagen fibrils, filaments and banded material similar to that found in the anterior part of Descemet's membrane observed between the endothelial cell layer and Descemet's membrane. The multilayered endothelial cell layer in our case was found to be strongly positive for cytokeratins K7 and KL1 and vimentin and negative for factor-VIII-related antigen, neuron-specific enolase, nerve tissue S-100 protein, epithelial membrane antigen, CD 68, actin and desmin. This immunohistochemical reaction pattern argues in favor of an epithelial origin for cells lining the endothelial cell layer in Chandler's syndrome.

Corneal Diseases↗

[Nodular and granulomatous form of periarteritis nodosa caused by the hepatitis B virus].

Polyarteritis nodosa (PAN) is, in rare cases, associated with subcutaneous nodules and pathology does not usually show the presence of peri and extravascular granulomas. When present in patients with hepatitis B virus (HBV) related PAN these facts demonstrate that classification of PAN is not homogeneous. CASE REPORT. A patient infected by HBV developed a PAN demonstrated by clinical symptoms and pathology. The disease was characterized by the presence of subcutaneous nodules and histologically by peri- and extra-vascular granuloma which surrounded necrosis of medium-sized vessels. Outcome was also unusual in the patient who did not respond to the association of plasma exchanges and antiviral agents and was only slightly improved by steroids and cyclophosphamide. COMMENTS. HBV-related PAN is considered to be an immune complex disorder. In the present case report granuloma were present as observed in Churg Strauss syndrome or Wegener's granulomatosis which are the consequence of other pathogenetic mechanisms as anticytoplasmic neutrophil antibodies (ANCA). This case reports underlines the heterogeneity of the PAN group of vasculitis and the probable role for various pathogenetic mechanisms.

Antiviral Agents↗

[Microbiological safety and endothelial quality control during preservation of corneal grafts at +31 degree C].

Over a 10-month-period, 59 corneas were organ-cultured at + 31 degrees C and 7 were preserved at + 4 degrees C. Among the 59 organ-cultured corneas, 41% (24) were grafted and 25% (15) developed an infection during preservation. At the time of surgery, preservation medium and scleral rim were tested for microbiology. Infection during preservation was bacterial (80%, 12/15) and fungal (20%, 3/12). Scleral rims were sterile in 96% (24/25) of the grafted corneas preserved at + 31 degrees C but 34% (2/6) at + 4 degrees C (p < 0.01). Preservation media were sterile in 100% (24/24) of organ-cultures at + 31 degrees C but in 83% cases (5/6) of preservations at + 4 degrees C (NS). The percentage of endothelial dead cells increased with postmortem enucleation delay (r = 0.43; p = 0.03). The average endothelial cell loss during organ-culture was 11.2% (+/- 10.4). It correlated with endothelial density (r = 0.42; p = 0.04) and with percentage of endothelial dead cells (r = 0.43; p = 0.04) after enucleation. Organ-cultured at + 31 degrees C was able to assess graft sterility in almost 100% of the cases but corneas are lost due to infection. Graft sterility is not usually possible with preservation at + 4 degrees C.

Aged↗

HTLV-1-like particles and HTLV-1-related DNA sequences in an unambiguous case of Sèzary syndrome.

An unambiguous case of Sèzary syndrome associated with the presence of unusual retroviral infection markers is described. The blood smear showed 15% typical Sèzary cells but also rare atypical lymphocytes with convoluted nuclei, evocative of characteristic adult T-cell leukemia (ATL) flower cells. However, the patient did not present any clinical or biological manifestations of ATL, and human T-cell leukemia virus type 1 (HTLV-1) serology was consistently negative. After being cultured for 4 months, peripheral blood mononuclear cells (PBMC) produced typical type C retrovirus-like particles with budding forms strongly resembling HTLV-1 virions. The producer cells did not express HTLV-1-specific antigens detectable by indirect immunofluorescence (IIF). Southern blotting of uncultured PBMC DNA, submitted to digestion with the restriction enzymes PstI and SacI, and hybridized with a full genomic HTLV-1 probe, showed the presence of specific homologous sequences, absent in all of the healthy donor control PBMC DNAs. These HTLV-1-like sequences presented a restriction enzyme pattern distinct from that of the HTLV-1 prototype genome and of other HTLV-1 proviruses studied up to now. Polymerase chain reaction (PCR) with highly conserved HTLV-1 derived pol and env primers was consistently negative with the patient's DNA. All these results taken together suggest that our patient carries a retroviral agent partially homologous to, but probably different from HTLV-1. The possibility is discussed that this type of retroviral agent might be associated with a subtype of cutaneous T-cell lymphoma (CTCL) represented by a typical Sèzary syndrome with a very low percentage of ATL-like flower cells in the blood smear.

Adult↗

[Astigmatism and its treatments].

Astigmatism is a refractive error related to corneal asphericity. Congenital astigmatism is most frequent, and its correction with spectacles has been known for a long time. Contact lenses may sometimes be useful, but they may not allow a satisfactory visual correction. Anterior segment surgery (cataract, penetrating keratopasty, etc.) may often cause postoperative astigmatism. Improvement in ophthalmic surgery, and the patient's need for a rapid and effective visual recovery (as anatomical result is obtained), have highlighted prevention and treatment of post-surgical astigmatism. Astigmatism treatment is complex and varies according to its intensity and cause. Refractive surgery, modifying corneal shape, may be an elegant solution in cases where vision is low, in spite of a perfect corneal transparency.

Astigmatism↗

Evaluation of the Tono-Pen 2 and the X-Pert noncontact tonometers in cataract surgery.

The Oculab Tono-Pen and the X-Pert noncontact tonometers (NCTs) were compared to the Goldmann applanation tonometer in a consecutive series of 45 patients before and after cataract surgery. In the preoperative period, the mean value of the paired difference at intraocular pressure (IOP) measurements was -1.30 +/- 2.11 mm Hg (mean +/- SD) for the X-Pert NCT (X-Pert NCT minus Goldmann) and -0.19 +/- 2.56 mm Hg for the Tono-Pen 2 (Tono-Pen 2 minus Goldmann). In the postoperative period, this mean difference was 0.26 +/- 2.45 mm Hg for the X-Pert NCT and 0.87 +/- 2.83 mm Hg for the Tono-Pen 2. We found 87 and 67% of the X-Pert NCT and the Tono-Pen 2 readings to be within +/- 2 mm Hg of the Goldmann readings, respectively. In both preoperative and postoperative eyes, correlation coefficients between the readings of the three instruments were high (ranging from 0.84 to 0.96). Differences between the three tonometers were not correlated with corneal thickness of corneal curvature postoperatively. Both Tono-Pen 2 and X-Pert NCT could thus be considered accurate instruments for IOP screening after cataract surgery when compared to the Goldmann applanation tonometer.

Cataract↗

A CD2+ subset of non-malignant peripheral blood lymphocytes from patients with Sézary syndromes overexpress the low-molecular-weight GTP-binding protein Rab2.

The Rab branch of the Ras-related GTP/GDP-binding proteins currently includes at least 25 related members which are involved in the intracellular vesicular transport along the secretory and endocytic pathways in eukaryotic cells. The overexpression of the Rab2 protein in peripheral mononuclear cells is demonstrated from 13 out of 17 patients exhibiting a Sézary syndrome. Moreover, this phenomenon is detectable in other lymphoid and myeloid malignancies. Several lines of evidence are shown suggesting that the Rab2 overexpression can be related not to leukemic cells but to a subset of peripheral lymphocytes with a CD2+ phenotype. Our results provides strong evidence for the implication of a small GDP/GTP-binding protein in immunological events associated with neoplastic states. The precise cellular population involved in this process remains to be determined.

Antigens, Differentiation, T-Lymphocyte↗

[Ultrastructural study of human cornea preserved in organ culture media at +31 degrees C].

Organ culture becomes a standard method of corneal graft preservation. The aim of the study was to evaluate the preservation injuries induced by organ culture. We examined 12 organ cultured human corneas. Corneas were preserved in the medium for 2 to 21 days. Corneas showed some abnormalities: numerous light vacuoles, mitochondrial swelling and increased cell thickness in all cells of the cornea, sloughing of the external and medium epithelial cell layers. We observed normal endoplasmic reticulum, Golgi apparatus and nucleus. These preservation injuries are moderate and reversible.

Aged↗

[Chronic blepharoconjunctivitis during a treatment with acitretin (Soriatane)].

We report external ocular side effects after treatment with acitretin, a new synthetic vitamin A analogue and the main metabolite of etretinate. A patient treated with 20-25 mg/day of acitretin for psoriasis suffered from chronic blepharoconjunctivitis. Schirmer tests, tear lysozyme were normal while rose bengal and fluorescein staining disclosed epithelial punctate defects and tear break-up time was shortened. Meibomian glands of the lower lid were photographed with transillumination and appeared atrophic. Conjunctival cytology and biopsy showed snake-like chromatine appearance, keratinized epithelial cells and some lymphocytes infiltrates. Accessory salivary gland histological aspects were nonspecific. There was a clear relationship between restarting the acitretin therapy and recurrence of ocular symptoms. Acitretin, like other retinoids, may induce or exacerbate blepharoconjunctivitis in patients with psoriasis.

Acitretin↗

Interleukin-7 is a growth factor for Sézary lymphoma cells.

Sézary syndrome is a cutaneous T cell lymphoma characterized by infiltration of the skin by CD4+ cells. These cells generally respond poorly to mitogens and T cell activators. We have studied the action of IL1 to IL4, IL6, and IL7 on the proliferation of Sézary cells from 12 patients. With the exception of IL2 and IL7, the cytokines studied had no proliferative effect on these cells. Whereas IL2 had only a low proliferative capacity (two- to threefold increase) on peripheral blood mononuclear cells, recombinant IL7 constantly induced a very significant (3-40-fold increase) proliferative response, and was used successfully to generate cell lines in three out of eight cases. Growth of Sézary cell lines was shown to be strictly dependent on IL7, and after 2-5 wk of culture presented a switch to a homogeneous phenotype CD3+4+8-7- (except for one line that remained CD7+), with a typical morphology of Sézary cells. Their tumoral origin was demonstrated by the expression of the same T cell receptor-beta gene rearrangement as the patients' T cells. Importantly, cultured normal epidermal keratinocyte supernatants could support the growth of our Sézary lines. Furthermore, the proliferative activity contained in these supernatants was completely blocked by a monoclonal anti-IL7 antibody. These results suggest that IL7 may, therefore, represent an important cytokine in the physiopathology of cutaneous T cell lymphoma.

Adult↗