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Biomedical subjects

B Berman

Publications and source records attributed to B Berman.

At least 73 records · Page 4Linked to original sources

Fulminant head and neck congestion in advanced cutaneous T cell lymphoma: a poor prognostic indicator.

BACKGROUND: Clinical factors associated with a poor prognosis in patients with cutaneous T cell lymphoma (CTCL) include the extent and type of skin involvement and the presence and extent of lymphadenopathy. MATERIALS: We report retrospectively the clinical course and survival time of four patients with advanced CTCL after the development of fulminant head and neck congestion. METHODS: All four patients presented with marked erythema and edema of the head and neck with marked cervical adenopathy. Treatment with multidrug chemotherapy and radiation induced only brief remissions. The clinical picture was felt to be due to extensive tumor infiltration of the skin as well as lymphatic compression due to cervical adenopathy rather than venous compression at the level of the mediastinum. Survival from onset of this fulminant head and neck congestion was 1-5 months. CONCLUSION: Development of this fulminant head and neck congestion in patients with advanced CTCL heralds a progressively deteriorating clinical course with a poor prognosis.

Adult↗

Mononuclear cells isolated from fibrotic skin lesions in avian scleroderma constitutively produce fibroblast-activating cytokines and immunoglobulin M.

University of California, Davis line 200 and 206 chickens develop an inherited autoimmune fibrotic disease associated with autoantibodies and other features similar to human scleroderma. Early in life, line 200/206 chickens develop mononuclear cell (MNC) infiltrates in the skin, followed by severe dermal fibrosis and vascular occlusions. Cultured fibroblasts derived from fibrotic skin lesions of line 200/206 chickens display an activated phenotype producing elevated quantities of collagen and glycosaminoglycan (GAG) compared to fibroblasts derived from normal chicken skin. To demonstrate a link between skin mononuclear cell infiltration and fibroblast activation, we cultured MNC isolated from developing fibrotic skin lesions, normal appearing skin, and peripheral blood of line 206 chickens for 24-72 h. Subsequent assay of MNC culture supernatants for effect on the collagen and GAG production of normal chicken skin fibroblasts demonstrated that only fibrotic lesion MNC supernatants contained significant collagen and GAG synthesis stimulatory activity. Both stimulatory activities were constitutively produced, undialyzable, heat and protease sensitive, and coeluted on gel filtration with a M(r) of 24-32 kD. Gel filtration also revealed that fibrotic lesion MNC secrete a protein > 250 kD, which we have identified as immunoglobulin (Ig) M by Western blot analysis. These results demonstrate that skin infiltrating MNC secrete both fibroblast-activating cytokines and IgM and thus they likely play an important role as effector cells in the development of dermal fibrosis and autoantibodies in this avian model of scleroderma.

Animals↗

Dermatologic uses of interferons.

Interferons are members of the cytokine family, with diverse antiviral, antiproliferative, antifibrotic, and immunomodulatory activities. Over the past 10 years, interferon use in clinical dermatology has extended beyond its historical antiviral efficacy. In this article, FDA-approved indications and non-FDA-approved dermatologic uses of interferons are reviewed.

Humans↗

Transient erythroblastopenia of childhood in infants < 6 months of age.

PURPOSE: During a 6-year period, we identified six infants < 6 months of age with transient erythroblastopenia of childhood (TEC). PATIENTS AND METHODS: All patients presented with moderate to severe anemia, reticulocytopenia, and age-appropriate mean corpuscular volume and fetal hemoglobin level. RESULTS: Severe aregenerative anemia in an infant < 6 months of age often raises the diagnostic possibility of Diamond Blackfan anemia (DBA). Given prognostic and therapeutic implications, distinction between DBA and TEC is of crucial importance. CONCLUSIONS: We suggest that TEC may occur more commonly in infants < 6 months of age than has heretofore been recognized and that it has a clinical and hematologic picture similar to that seen in older children. Recognition of the occurrence of TEC in very young infants may help avoid an inappropriate diagnosis of DBA.

Age Factors↗

Short versus long echo time for cranial MR angiography in children and adults.

PURPOSE: To evaluate the ability of short-echo-time (TE) versus long-TE three-dimensional time-of-flight MR angiography sequences to decrease phase-related signal loss and refocus signal from blood in intracranial MR angiography of adults and children. METHODS: We evaluated 3-D time-of-flight cranial MR angiography in 33 cases (18 children and 15 adults) using two sequences. The longer-echo reference sequence had a TE of 8.0 milliseconds and a field echo of 6.5 milliseconds; the shorter-echo sequence had a TE of 5.1 and a field echo of 4.2 milliseconds. Repetition time, flip angle, and matrix were constant. The bandwidth for the longer-echo sequence was 130 Hz, 195 Hz for the shorter-echo sequence. RESULTS: The greatest improvement in diagnostic images was for children; significant and mildly improved signal recovery was demonstrated in 15 and 2 cases, respectively, of a total of 18 studies. This allowed improved diagnostic assessment. However, in the adult group significantly and mildly improved signal recovery were present in only 2 and 6 cases, respectively, of a total of 15 studies. In the group of children and adults combined, decreased lumen definition and peripheral vessel visibility were present in 24 and 30 of 33 cases, respectively, because of higher signal from background tissue when the shorter-TE field-echo sequence was used and, hence, reduced vascular contrast. CONCLUSION: The use of a short-field-echo/TE sequence is therefore recommended as the initial study in children but as a secondary examination in areas of abnormality in adults. This study illustrates the improved signal recovery from phase-related sources and improved visibility of intracranial stenosis in children with the use of a short-echo sequence. In adults, the short-echo sequence should not be used for the initial screening but reserved for secondary evaluation.

Adolescent↗

Nonradioactive gel mobility shift assay using chemiluminescent detection.

A nonradioactive gel mobility shift assay using chemiluminescent detection following semidry transfer to nylon membranes is described. The procedure utilizes digoxigenin-labeled oligonucleotides in conjunction with anti-digoxigenin antibody Fab fragments coupled to alkaline phosphatase. Detection of alkaline phosphatase is by autoradiography of the chemiluminescence produced during enzymatic dephosphorylation of a dioxetane substrate. This method offers similar sensitivity to radioactive methods while having the advantages of multiple exposures, faster processing, stability of labeled oligonucleotides and safety associated with nonradioactive methods of detection.

DNA-Binding Proteins↗

Efficacy of a 1-week, twice-daily regimen of terbinafine 1% cream in the treatment of interdigital tinea pedis. Results of placebo-controlled, double-blind, multicenter trials.

BACKGROUND: Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve. The result is an incomplete cure/recurrence. OBJECTIVE: Terbinafine, a topical fungicidal agent, was evaluated in double-blind, placebo-controlled trials (159 patients) for its ability to achieve cure and relief of symptoms in the same time frame, that is, before compliance wanes. METHODS: Mycologic characteristics (with potassium hydroxide examination and culture) and clinical signs and symptoms were assessed at baseline, at the end of a 1-week, twice-daily treatment and at 1, 3, and 5 weeks after the completion of therapy. RESULTS: Both terbinafine and vehicle provided early relief of symptoms. However, only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment, 88% of the patients receiving terbinafine had converted from positive to negative mycology compared with 23% of the patients treated with vehicle. CONCLUSION: The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by non-compliance.

Antifungal Agents↗

Cultured fibroblasts in avian scleroderma, an autoimmune fibrotic disease, display an activated phenotype.

University of California, Davis, line 200 and 206 chickens spontaneously develop an autoimmune syndrome that has many features analogous to human scleroderma, including dermal fibrosis, antinuclear antibodies and antibodies to type II collagen. These birds also have thymic subcapsular epithelial defects and an abnormality in T cell calcium influx and proliferation in response to both T cell receptor-dependent and -independent activators. To determine whether fibroblast activation is a contributing factor to development of skin fibrosis in line 200/206 chickens, as it is in human scleroderma, we studied the collagen, non-collagenous protein and glycosaminoglycan (GAG) production of 34 separate fibroblast lines derived from the normal and fibrotic skin of line 200 and 206 chickens and from the skin of control chicken lines 058 and 254. The mean +/- SEM 24-h incorporation of 3H-proline or 3H-glucosamine into extracellular collagen, non-collagenous protein or GAG by first passage fibroblast lines derived from the fibrotic skin of diseased birds was 1,526 +/- 136, 859 +/- 82 and 25.7 +/- 1.3 dpm/10(3) cells, respectively, while fibroblast lines derived from the skin of control birds produced only 341 +/- 36, 343 +/- 42 and 15.2 +/- 1.4 dpm/10(3) cells. Similar differences in results were recorded for cell-associated production, and when collagen and non-collagenous protein production were assessed using non-radioactive electrophoretic methods. The activated phenotype of the fibroblast lines derived from the fibrotic skin of diseased birds persisted through 10 cell doublings in tissue culture. However, the ratio of type I:III collagen and the profile of GAG types produced were similar in all fibroblast lines studied. These results suggest that fibroblast activation is responsible for the skin fibrosis observed in this avian model of scleroderma.

Animals↗

Tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) receptors on human normal and scleroderma dermal fibroblasts in vitro.

Interferons alpha and gamma (IFN-alpha, IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) exert different regulatory effects on the proliferation and biosynthetic activities of human dermal fibroblasts. Inasmuch as these cytokines bind to specific receptors in order to exert their activities, the expression of IFN-alpha, IFN-gamma and TNF-alpha receptors on fibroblasts from human adult normal and scleroderma skin cultured in vitro were quantitated. Adsorption was detected by incubating confluent normal and scleroderma fibroblasts with various concentrations of [125I]cytokine. Replicate experiments revealed 19,742 +/- 2057 (Kd = 1.15 x 10(-9) M) TNF-alpha receptors per normal dermal fibroblast and 15,006 +/- 75 (Kd = 6.75 x 10(-10) M) TNF-alpha receptors per scleroderma fibroblast. Cross-linking 125I-TNF-alpha to its receptor on normal and scleroderma fibroblasts revealed 130- and 100-kDa TNF-receptor complexes. Although no quantitative or qualitative differences were detected between these two cell types with regard to receptor numbers, TNF-alpha affinity or receptor protein as detected by radiolabelled TNF-alpha, differences were detected in levels of mRNA specific for TNF-alpha receptors. Northern blot analysis revealed normal fibroblasts to constitutively contain mainly mRNA specific for the 55-kDa TNF receptor and indicate that they are capable of responding to TNF-alpha-induced up-regulation of mRNA specific for the 75 kDa TNF receptor. Scleroderma fibroblasts, however, constitutively contain mRNA for both TNF receptors and fail to respond to TNF-alpha up-regulation of the message for the 75-kDa receptor for TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokines↗

Epidemiology of dermatitis among California farm workers.

To estimate the prevalence of dermatitis and risk factors for skin disease in California farm workers, a cross-sectional survey was conducted among grape, citrus, and tomato workers. The prevalence of contact dermatitis was 2% and lichenified hand dermatitis was 13%. Grape workers were more likely to report rashes in the last 12 months than were tomato workers or citrus workers. Grape workers were more likely to have contact dermatitis and lichenified hand dermatitis than were citrus or tomato workers. Increasing hours per week in agriculture, male sex, and not wearing gloves were associated with more lichenified hand dermatitis. We conclude that skin disease in agricultural workers may be causally associated with crop-specific exposures and lack of protective equipment.

Adult↗

Pentoxifylline inhibits certain constitutive and tumor necrosis factor-alpha-induced activities of human normal dermal fibroblasts.

Pentoxifylline (PFN), analog of theobromine, which phenotypically and functionally alters various cell types including dermal fibroblasts, has been reported to inhibit tumor necrosis factor-alpha (TNF alpha) activation of neutrophils. We investigated the ability of PFN to alter constitutive and TNF alpha-induced biosynthetic activities of human normal dermal fibroblasts. The sixteenfold increase over constitutive intracellular 2'-5' oligo-adenylate synthetase (2'-5' A synthetase) activity induced by TNF alpha (400 U/ml) failed to occur when PFN (1 mg/ml) was added prior to cytokine treatment. This loss of biologic activity paralleled a reduction in 2'-5' A synthetase proteins and 2'-5' A synthetase-specific m-RNA. PFN failed to inhibit constitutive or TNF alpha-induced IL-6 hybridoma proliferative activity, IL-6 protein, or IL-6-specific m-RNA levels. The presence of PFN (1 mg/ml) in fibroblast cultures reduced constitutive synthesis of collagen and glycosaminoglycan (GAG) by 87% and 45%, respectively, and blocked induction of their synthesis by TNF alpha (10(4) U/ml). Total non-collagenous protein synthesis was not inhibited following PFN treatment (1 mg/ml). PFN did not inhibit TNF alpha induction of only those biosynthetic activities also susceptible to PFN in the constitutive state, with PFN failing to reduce constitutive collagenolytic activity but reducing TNF alpha-induced enhanced collagenolytic activity by 26% and collagenase m-RNA by 51%. Furthermore, PFN did inhibit, by 98%, TNF alpha-dependent murine and human fibroblast cytotoxicity. The selective nature of PFN inhibition of certain TNF alpha activities, the failure of PFN (1 mg/ml) to alter constitutive and TNF alpha-induced levels of type 1 and 2 TNF alpha receptor m-RNA, and the finding that PFN-treated fibroblasts express a similar number of receptors, of similar molecular weight and high affinity for TNF alpha as control, untreated cells, suggest that inhibitory activities of PFN are mediated at a locus other than receptors for TNF alpha.

2',5'-Oligoadenylate Synthetase↗

Characterization of a glucocorticosteroid-induced inhibitor of interferon-gamma induction of HLA-DR expression.

Interferon gamma (IFN-gamma) induces human leukocyte antigen (HLA)-DR antigen expression on a variety of cell types, and in human skin cells this induction is inhibited by trypsin inhibitors. Recently a trypsin-like protease was characterized whose activity is required for HLA-DR induction in a hybrid epidermal cell line. Glucocorticosteroids also inhibit IFN-gamma-induced HLA-DR expression, and similarities have been noted between the inhibition by trypsin inhibitors and by glucocorticosteroids. To assess the possibility that glucocorticosteroid inhibition of IFN-gamma-induced HLA-DR expression might be due to induction of an inhibitor of trypsin activity that is re-expression, we examined culture medium supernates (CM) of glucocorticosteroid-treated cells for HLA-DR- and trypsin-inhibitory activities. We report here that CM of glucocorticosteroid-treated H12 cells contain inhibitors of HLA-DR expression and of trypsin activity, but that the two inhibitors are not identical. H12 cells constitutively secrete a greater than 30,000 MW, acid- and heat-stable trypsin inhibitor, whose expression is not modulated by glucocorticosteroid or IFN-gamma, and that does not inhibit IFN-gamma-induced HLA-DR expression. The HLA-DR inhibitor, on the other hand, is present only in CM of glucocorticosteroid-treated cells, is distinct from glucocorticosteroid itself, of a MW less than 500 and does not inhibit trypsin. We conclude, therefore, that the glucocorticosteroid inhibition of IFN-gamma-induced HLA-DR expression is by a mechanism other than secretion of a trypsin inhibitor.

Cells, Cultured↗

Self-regulation and assessment approaches for vaso-occlusive pain management for pediatric sickle cell anemia patients.

An interdisciplinary program with the goal of teaching self-regulation and minimizing excessive narcotic use in the management of vaso-occlusive pain (V-O) in pediatric sickle cell anemia patients is described. A small group of patients do not respond well to any of our outpatients or inpatients medical regimens, leading us to suspect that psychological factors are influencing pain reports. We outline our multi-faceted assessment approach to evaluating such psychological factors, which includes a pain flow sheet, symptom check list, and a psychophysiologic profile. Published reports of self-regulation training including biofeedback, relaxation/imagery, and hypnosis have been associated with decreased pain symptoms, reduced number of emergency room and hospital visits for pain, decreased narcotic use, and increased school attendance. A case study of a nine-year-old patient with sickle cell disease is described before and after self-regulation training. Finally, other alternative approaches that avoid excessive narcotic use are discussed with some case reports.

Adaptation, Psychological↗

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN: Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS: Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS: This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.

Adult↗