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Biomedical subjects

M Duvic

Publications and source records attributed to M Duvic.

At least 55 records · Page 3Linked to original sources
PubMed1999

Prognostic factor analysis in mycosis fungoides/Sézary syndrome.

BACKGROUND: The influence of prognostic factors on survival in patients with mycosis fungoides/Sézary syndrome (MF/SS) is less well described than for other lymphomas. OBJECTIVE: Our purpose was to evaluate the prognostic value of diverse clinicopathologic and laboratory characteristics in patients with MF/SS. METHODS: All 115 patients with MF/SS seen at the Mycosis Fungoides clinic at M. D. Anderson Cancer Center during the study period who had slides available for pathologic review were analyzed. Univariate and multivariate methodologies were used. RESULTS: Age (> or = 60 years; P = .0002), advanced stage (P < 10(-5)), tumor (T3) stage disease (P < or = 10(-5)), lymphadenopathy (P = .006), bone marrow infiltration (P = .03), high lactate dehydrogenase (LDH; P = .0002), high beta2-microglobulin (> 2 mg/L; P = .009), and transformation to large-cell lymphoma (P = .004) were significant prognostic factors in the univariate analysis and correlated with a poorer survival. The outcome of patients staged as IIB was significantly worse than that of those staged as I or IIA or III (P < .001) and was comparable to that of the patients staged as IV (P = .8). In the multivariate analysis, the factors selected include stage (I to IIA and III vs IIB and IV; P < .0001), LDH (P = .006), and age (> or = 60 vs < 60 years; P = .02). The actuarial median survival of patients with advanced stage, high LDH, or age 60 years or more was 2.5 to 3.5 years, whereas that of patients without any of these parameters was more than 13 years. CONCLUSION: Our results suggest that patients with MF/SS who are staged as IIB or IV, who have a high LDH, or who are 60 years of age or older have an aggressive course and poor survival.

Bone Marrow↗
PubMed1999

Alterations in HIV expression in AIDS patients with psoriasis or pruritus treated with phototherapy.

BACKGROUND: Ultraviolet light (UVL) upregulates HIV transcription in vitro and in transgenic mice. AIDS-associated psoriasis and pruritus respond to phototherapy. OBJECTIVE: Our goal was to determine the effect of phototherapy on viral load and immunologic parameters in HIV-positive patients. METHODS: T cell subsets, p24, plasma cytokines, serum or plasma HIV-RNA, dosage, and antivirals were assessed in HIV-positive patients and negative controls receiving 6 weeks of phototherapy with UVB and in untreated controls. RESULTS: Phototherapy improved skin conditions without significantly affecting T cell numbers. Plasma p24 increased 2-fold (P = .055) and HIV-RNA levels 4-fold (P = .022) 6 weeks from baseline in patients who entered the trial before March 1995. Later patients who were mostly receiving combination antiviral therapy showed a 4-fold reduction in serum HIV-RNA (P = .012) at 2 weeks. The effect of UVB on viral load at 6 weeks was dependent on the baseline level (P = .006). IL-10 increased and was inversely related to HIV-RNA levels (P = .0267). CONCLUSION: Phototherapy is associated with HIV load alterations, depending on patients' initial HIV-RNA, antiviral therapy, skin type, and UVL dosage.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Interleukin-10 levels are often elevated in serum of adults with Hodgkin's disease and are associated with inferior failure-free survival.

BACKGROUND: Interleukin-10 (IL-10) is a pleiotropic cytokine that protects B- or T-lymphocytes and hemopoietic progenitors from apoptosis induced by doxorubicin, glucocorticoids, or deprivation of growth factors. IL-10 is also immunosupressive, and tumor cells secreting IL-10 can grow in syngeneic or allogeneic hosts, and can inhibit the generation of tumor-specific cytotoxic T cells. Hodgkin-Reed-Sternberg cells are derived from follicular center B cells and they may be latently infected by EBV. When this occurs they often express IL-10. Based on these considerations we investigated the relationship between pretreatment serum IL-10 levels and failure-free survival (FFS) in Hodgkin's disease (HD). PATIENTS AND METHODS: Untreated patients, older than 16 years, with biopsy-proven HD, were included if treated with ABVD or equivalent regimens, and if pretreatment serum was available. IL-10 levels were determined with a capture enzyme-linked immunoassay specific for cellular IL-10. RESULTS: Among healthy adult volunteers serum IL-10 levels ranged from 4.8-9.8 pg/ml (mean 7.1, standard deviation 1.5 pg/ml). Therefore levels > or = 10 pg/ml were considered elevated. We identified 101 patients with available serum. Their median age was 32 years, and 60% had B-symptoms. Ann Arbor stage was I in 4, II in 21, III in 35, and IV in 41 patients. Histology was nodular sclerosis in 74, mixed cellularity in 12, lymphocyte predominance in six, lymphocyte depletion in one, and unclassified in eight patients. Pretreatment serum IL-10 levels were elevated in 51 patients, and were higher in those with serum albumin < 3.5 g/dl, B symptoms, serum beta 2-microglobulin > or = 2.5 mg/l, anemia, and AAS III or IV. After a median follow-up of 32 months for survivors, 20 patients have progressed, and the three-year FFS of those with high vs. normal serum IL-10 was 60% +/- 9 vs. 91 +/- 9% (50% vs. 50% of the population; P = 0.004 by log-rank). Among patients with Ann Arbor stage III or IV the three-year FFS for those with high vs. normal serum IL-10 (58 vs. 42% of the population) was 57 +/- 9% vs. 92 +/- 6% (P = 0.008 by log-rank). Multivariate analysis using Cox's proportional hazards model confirmed that IL-10 was an independent variable associated with inferior FFS in this population. CONCLUSIONS: Elevation of serum IL-10 levels is frequent and is associated with inferior FFS in adults with ABVD-treated HD. This observation should be verified in other patient populations. In addition, the source and the role of IL-10 in the biology of HD should be further investigated.

Adolescent↗
PubMed1999

Alopecia areata in families: association with the HLA locus.

Alopecia areata (AA) is a T cell mediated disease directed against hair follicles that results in bald patches. It can range in severity from patchy (AA), to total scalp hair loss (alopecia totalis; AT) or body hair loss (alopecia universalis; AU). We have previously shown that HLA-DR4 and DR11 as well as HLA-DQ*03 alleles are increased in unrelated AA patients compared with controls. To study whether class II HLA alleles are linked to AA, we investigated 81 extended families that included 192 AA patients, including 89 with AT or AU. We also performed the transmission disequilibrium test (TDT) in 143 nuclear families. Results showed an association between alleles of HLA-DQB (p = 0.014) and HLA-DR (p = 0.010). We also performed linkage analysis in 75 families whose members' genomic DNA were available for HLA typing. Results from this analysis support linkage between AA and class II loci with a maximal LOD score of 2.42 to HLA-DQB at 5% recombination, and with a maximal LOD score of 2.34 to HLA-DR at 0% recombination. There was an increased incidence of atopic dermatitis and autoimmune thyroiditis in families. AA appears to be a class II HLA restricted organ specific immune response to the hair follicle.

Alleles↗
PubMed1999

Dysregulated synthesis of intracellular type 1 and type 2 cytokines by T cells of patients with cutaneous T-cell lymphoma.

Mycosis fungoides (MF) and Sezary syndrome (SS) are the two main clinical entities of cutaneous T-cell lymphoma (CTCL). As the disease progresses from MF to SS, a switch from a type 1 (interleukin [IL]-2 and gamma interferon [IFN-gamma]) to a type 2 (IL-4) cytokine production profile occurs. Although roles for type 1 and type 2 cytokines in the pathogenesis of CTCL have been proposed, the cellular origins of these cytokines are unclear. Using flow cytometry to identify individual T-cell subsets, we studied cytokine synthesis by the T cells of 13 patients with SS and 12 with MF and 9 hematologically healthy donors. Upon activation with phorbol 12-myristate 13-acetate (PMA), the numbers of T cells synthesizing IL-2 were similar for all study groups. Whereas the predominant T-cell producing IL-2 in healthy donors and in those with MF was CD7(+), in patients with SS, it was CD7(-). Although the number of IL-4(+) CD4(+) T cells was low for all study groups, there was a significantly higher number of IL-4(+) CD8(+) T cells in patients with MF than in those with SS or healthy donors. There was a decline in the number of IFN-gamma-producing T cells in CTCL donors compared to that in healthy donors. More importantly, there was a significant decrease in the number of IFN-gamma-producing T cells with disease progression from MF to SS. The inability of these T cells to synthesize IFN-gamma may have prognostic value in CTCL, since it may be responsible for the progression of the disease from MF to SS.

Case-Control Studies↗
PubMed1999

Pentostatin therapy of T-cell lymphomas with cutaneous manifestations.

PURPOSE: To determine the side effects of and response to pentostatin in patients with T-cell lymphomas with cutaneous manifestations. PATIENTS AND METHODS: Pentostatin was administered to 28 patients who had relapsed cutaneous T-cell lymphoma or peripheral T-cell lymphoma with prominent cutaneous disease. The starting dose was between 3.75 to 5.0 mg/m(2)/d intravenous for 3 days every 3 weeks. RESULTS: Of the 24 patients assessable for response, 17 (71%) achieved a partial remission (46%) or complete remission (25%). The patients had a median number of three (range, one to 12) prior therapies. Of the 86 courses of pentostatin given, 39 were administered at doses of 5.0 mg/m(2)/d and 30 at doses of 3. 75 mg/m(2)/d. Dose escalation to 6.25 mg/m(2)/d was possible in only five courses, and toxicity necessitated dose reduction to 2.8 mg/m(2)/d in 12 courses. The most common side effects were granulocytopenia, nausea, and nonneutropenic fever. Most patients developed significant lowering of CD4 counts. Herpes zoster was seen within 1 year after pentostatin in five patients (19%). CONCLUSION: Pentostatin is an active agent in heavily pretreated T-cell lymphomas with cutaneous manifestations.

Adult↗
PubMed1998

Identification and characterization of a retinoid-induced class II tumor suppressor/growth regulatory gene.

Retinoids, synthetic and natural analogs of retinoic acid, exhibit potent growth inhibitory and cell differentiation activities that account for their beneficial effects in treating hyperproliferative diseases such as psoriasis, actinic keratosis, and certain neoplasias. Tazarotene is a synthetic retinoid that is used in the clinic for the treatment of psoriasis. To better understand the mechanism of retinoid action in the treatment of hyperproliferative diseases, we used a long-range differential display-PCR to isolate retinoid-responsive genes from primary human keratinocytes. We have identified a cDNA, tazarotene-induced gene 3 (TIG3; Retinoic Acid Receptor Responder 3) showing significant homology to the class II tumor suppressor gene, H-rev 107. Tazarotene treatment increases TIG3 expression in primary human keratinocytes and in vivo in psoriatic lesions. Increased TIG3 expression is correlated with decreased proliferation. TIG3 is expressed in a number of tissues, and expression is reduced in cancer cell lines and some primary tumors. In breast cancer cell lines, retinoid-dependent TIG3 induction is observed in lines that are growth suppressed by retinoids but not in nonresponsive lines. Transient over-expression of TIG3 in T47D or Chinese hamster ovary cells inhibits colony expansion. Finally, studies in 293 cells expressing TIG3 linked to an inducible promoter demonstrated decreased proliferation with increased TIG3 levels. These studies suggest that TIG3 may be a growth regulator that mediates some of the growth suppressive effects of retinoids.

Amino Acid Sequence↗
PubMed1998

Transformation of mycosis fungoides/Sezary syndrome: clinical characteristics and prognosis.

The occurrence of large cell transformation has been well documented in a subgroup of patients with mycosis fungoides/Sezary syndrome (MF/SS). However, because of the rarity of MF/SS, little is known about the influence of clinicopathologic features in predicting large cell transformation and about outcome in the transformed cases. We evaluated all patients with MF/SS who were registered in our clinic during the study period and for whom pathologic slides for review were available or could be obtained. Disease was classified as transformed if biopsy showed large cells (>/=4 times the size of a small lymphocyte) in more than 25% of the infiltrate or if they formed microscopic nodules. Twenty-six patients with transformation were identified from a total of 115 evaluable cases with a diagnosis of MF/SS. The actuarial cumulative probability of transformation reached 39% in 12 years. The median time from diagnosis of MF/SS to transformation was 12 months (range, 0 to 128 months). Thirty-one percent of all patients with stage IIB-IV disease at presentation eventually transformed versus 14% of those with stage I-IIA (P = . 03), with transformation being especially common in patients with tumors (T3), 46% of whom transformed. Combining elevated beta2 microglobulin and lactic dehydrogenase (neither elevated v one or both elevated) was also predictive for transformation (P = .009). The median survival from initial diagnosis of MF/SS for the transformed patients was 37 months versus 163 months for the untransformed group (P = .0029). The median survival from transformation was 19.4 months (range, 2+ to 138 months). The following characteristics were associated with an inferior survival in transformed patients: (1) early transformation (<2 years from the diagnosis v >/=2 years; P = .011) and (2) advanced stage (IIB-IV v I-IIA; 2-year survival, 23% v 86%; P = .0035). We conclude that MF/SS patients with stages IIB-IV disease and, in particular, those with tumors have a high incidence of large-cell transformation. Patients with transformation have a relatively poor survival, especially if transformation occurs early (within 2 years) in the course of disease or if they are staged as IIB or higher.

Actuarial Analysis↗
PubMed1998

DAB389IL2 diphtheria fusion toxin produces clinical responses in tumor stage cutaneous T cell lymphoma.

Four patients with late stage cutaneous T cell lymphoma (IB-IVA) who had failed at least two previous therapies were treated with DAB389IL2 at 9 or 18 microg/kg as 15-min intravenous infusions daily for 5 days every 3 weeks for eight cycles. Mild vascular leak syndrome (VLS) with transient edema, hypoalbuminemia, weight gain, and myalgias was observed in two of the patients lasting 7-10 days and only occurring on the first cycle. One stage IB patient had a pathologic complete remission (CR) lasting 11+ months from treatment initiation, one stage IIB patient had a complete clinical remission (CCR) lasting >6 months with complete clearing of a large tumor lasting >18 months, and one stage IIB and the one stage IVA patient had partial remissions (80-99% reduction in tumor masses) lasting 5 months. While IL2 receptor (IL2R) was expressed on 20-50% of tumor cells prior to therapy, recurrent tumor was IL2R negative in three of the patients. DAB389IL2 at tolerable doses decreased tumor burden in each of these four standard treatment refractory CTCL patients and may offer an important alternative to standard palliative chemotherapy regimens.

Administration, Topical↗
PubMed1998

Nerve growth factor in normal and psoriatic skin equivalent models.

Our objective was to determine the pattern and time course of nerve growth factor expression in an established skin equivalent model that we have used in the past to study wound healing and psoriasis phenotypes. Skin equivalents were constructed in triplicate using normal neonatal foreskin keratinocytes plated on collagen gels containing fibroblast lines. These lines were derived from five specimens of psoriatic lesions, three specimens of normal skin from patients with psoriasis, and three specimens of eyelid skin from normal donors. Immunohistochemistry and a monoclonal nerve growth factor-b antibody were used to determine the pattern of protein staining over 2 weeks. We looked at the wound healing phenotype using the skin equivalent model for 7-14 days. When keratinocytes invaginate into the dermis of skin equivalents (beginning at around 7 days of growth), dark staining of nerve growth factor was seen under the basal membrane zone, suggesting that nerve growth factor serves in the development of the basal membrane zone and the epidermis, and may influence the migration of nerves through the basal membrane zone into the regenerated skin.

Cells, Cultured↗
PubMed1998

The pathogenesis of psoriasis and the mechanism of action of tazarotene.

The 3 major features of psoriasis--abnormal differentiation of keratinocytes, hyperproliferation of keratinocytes, and infiltration of inflammatory components into the skin--can be quantified by measuring levels of certain biochemical markers. Psoriasis is associated with upregulation or downregulation of several of these markers. Tazarotene helps to normalize the levels of the markers, thereby bringing about clinical improvement.

Administration, Cutaneous↗
PubMed1998

Antinuclear antibody seropositivity in patients with cutaneous T-cell lymphoma.

BACKGROUND: We attempted to determine the frequency and clinical relevance of antinuclear antibody (ANA) testing and positive ANA test results in patients with cutaneous T-cell lymphoma (CTCL). METHODS: A retrospective chart and computer record review was conducted to determine the frequency of ANA testing in CTCL patients and the rate of seropositivity. Patients with a positive ANA were further examined to define possible explanations of the positive test. RESULTS: Of 381 patients with CTCL, 66 (17%) had ANA tests; 8 of these (12.1%) were found to have an ANA titer greater than or equal to 1:40. Of patients with a positive ANA test, one was found to have chronic cutaneous lupus erythematosus histologically and clinically mimicking CTCL. Others were found to have a comorbid connective tissue disorder, some had apparent drug-induced antinuclear antibodies, and some had no identifiable reason for a positive ANA test. CONCLUSION: ANA seropositivity does not appear to be increased in CTCL patients, and the ANA test remains a useful screening tool for differentiating between CTCL and connective tissue disorders.

Adult↗
PubMed1998

Unusual presentation of mycosis fungoides as pigmented purpura with malignant thymoma.

Thymoma is known to be associated with many lymphoreticular and nonlymphoreticular tumors. A woman who presented with patch stage mycosis fungoides with skin lesions resembling a pigmented purpura was found to have an anterior mediastinal mass on routine staging evaluation. A core needle biopsy of the mass revealed a lymphocyte predominant malignant thymoma. Review of the literature reveals many diseases with dermatologic manifestations associated with thymoma; however, malignant thymoma coexisting with mycosis fungoides has not previously been reported.

Adult↗
PubMed1998

Alopecia areata and cytomegalovirus infection in twins: genes versus environment?

BACKGROUND: Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease mediated by T cells directed to the hair follicle. Genetic susceptibility may be conferred by HLA, and an environmental trigger, such as a viral infection, is suspected. The incidence of AA in the population is estimated to be 1.7%, with an average of one in four patients having a positive family history. OBJECTIVE: Our purpose was to examine the concordance rate of AA among identical versus fraternal twins and the correlation between stress, cytomegalovirus (CMV) infection, and disease. METHODS: Families with AA were solicited from dermatologists in the United States and through a Website on the Internet. HLA class 2 typing and identification of CMV early and late genes were performed by polymerase chain reaction (PCR) on genomic peripheral blood DNA. Serum antibodies for CMV were determined by enzyme-linked immunosorbent assay. RESULTS: From 114 families, we identified 11 sets of monozygotic twins and 3 sets of dizygotic twins. The concordance rate was 55% for monozygotic twins and 0% for fraternal twins. Most identical twins were male. The severity of the AA phenotype varied and appeared most severe in the first affected twin. Five of 24 twins were CMV seropositive but CMV DNA was not detected in blood lymphocytes of any of the subjects when studied after the onset of AA. The presence of AA in twins was not correlated with evidence of CMV. CONCLUSION: A 55% concordance rate in identical twins and AA occurring in families support a genetic component as well as possible environmental triggers that remain unknown.

Adolescent↗
PubMed1998

Mycosis fungoides with focal segmental glomerular sclerosis and nephrotic syndrome.

Cutaneous T-cell lymphoma includes mycosis fungoides and the leukemic variant, Sézary syndrome. We report the first two cases of focal segmental glomerulosclerosis in patients with cutaneous T-cell lymphoma, with nephrotic range proteinuria and review the literature on renal disease coexisting with cutaneous T-cell lymphoma. We hypothesize that glomerular injury in cutaneous T-cell lymphoma may be related to interleukin-2.

Biopsy↗
PubMed1998

Distinct serum cytokines in AIDS-related skin diseases.

To determine whether common skin diseases associated with human immunodeficiency virus (HIV) were distinguishable based on the pattern of serum cytokine expression, we studied patients with psoriasis, pruritus, and Kaposi's sarcoma (KS) for levels of tumor necrosis factor (TNF)-alpha, interferon-gamma (IFN-y), interleukin (IL)-10, and IL-4. Thirty-two HIV-positive (HIV+) patients including 8 with KS, 11 with psoriasis, and 13 with pruritus along with 16 HIV-negative subjects with psoriasis were studied. IFN-gamma levels were highest in sera of HIV+ patients with psoriasis (p = 0.040). By contrast, TNF-alpha and IL-10 levels were highest in sera of HIV+ patients with pruritus (p = 0.012). Detectable levels of all cytokines in these patients were remarkably higher than for healthy adults. These results suggest that common skin diseases associated with HIV infection and AIDS can be distinguished by the production of unique cytokines.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Artificial skin equivalent differentiation depends on fibroblast donor site: use of eyelid fibroblasts.

Our objective was to construct and explore human skin equivalents from several normal and pathologic donor skin sites to determine if the fibroblast origin influences epidermal differentiation. Also, we wanted to find out if fibroblasts from some donor sites produced epidermis of superior quality for plastic surgery repairs. Skin equivalents were constructed from 15 normal skin specimens, 9 normal eyelid specimens, 15 lesional skin specimens taken from patients with psoriasis, and 4 specimens from keloid scars. Results show that the tissue origin of the donor fibroblasts determines epidermal differentiation and the time period for regeneration. Eyelid fibroblasts were very dependable in establishing well-differentiated skin equivalents in all nine specimens. Our findings contribute to the accumulated knowledge of wound healing and should also be of value in skin grafting, especially when large areas are denuded as in burns, severe trauma, or cancer ablation.

Adolescent↗