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Biomedical subjects

J M Gelfand

Publications and source records attributed to J M Gelfand.

12 recordsLinked to original sources

Pleiotrophin expression correlates with melanocytic tumor progression and metastatic potential.

BACKGROUND: Gene expression profiling of melanoma and nevic tissue has demonstrated that pleiotrophin (PTN) is significantly overexpressed in human melanomas. METHODS: To further evaluate PTN expression in melanocytic lesions, protein immunohistochemistry was performed on the spectrum of melanocytic lesions. RESULTS: Melanocytic nevi were consistently negative (n=58). In contrast, the great majority of metastatic melanomas were positive (33/34, 97%). The analysis of 34 primary melanomas demonstrated PTN positivity in 20 lesions while 14 lesions were negative. Within the primary melanomas, PTN immunoreactivity was associated with metastasis (p=0.0004) and decreased melanoma-related survival (p=0.0444). Univariate analysis of PTN immunoreactivity predicted an increased risk for metastasis (relative risk 9.1, p=0.003). CONCLUSIONS: The results of this study confirm previous gene profiling data showing differential PTN expression between melanocytic nevi and melanomas. In addition, lesional PTN expression is associated with metastatic potential and may be a prognostic factor for melanomas.

Adult↗

Dermatofibrosarcoma protuberans in two patients with acquired immunodeficiency syndrome.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous tumor of intermediate malignancy. Most commonly, it arises as an asymptomatic, indurated plaque on the trunk within which protuberant nodules develop over time. We describe its occurrence in two patients with human immunodeficiency virus, a previously unreported association. The first patient, a 41-year-old woman, complained of painful lesions around the left shoulder that developed within a scar from previous trauma to the area. The second patient, a 50-year-old man, developed a recurrent DFSP within the scar from a previous surgical procedure. Dermatofibrosarcoma protuberans was confirmed in both cases by the histopathologic and immunohistochemical findings.

Acquired Immunodeficiency Syndrome↗

Generation of a tropoelastin mRNA variant by alternative polyadenylation site selection in sun-damaged human skin and ultraviolet B-irradiated fibroblasts.

The goal of this research was to delineate the post-transcriptional mechanisms responsible for the increased elastin synthesis characteristic of sundamaged skin. In this study, a unique molecular variant of the tropoelastin mRNA transcript was identified in human sundamaged skin that was derived from the usage of an alternate polyadenylation site. Nonsolar exposed human skin expressed one tropoelastin mRNA species whereas sundamaged human skin expressed the primary tropoelastin mRNA and a larger, alternate tropoelastin mRNA formed from the utilization of a second polyadenylation site. Cultured human skin fibroblasts expressed both tropoelastin transcripts and in vitro UV treatment increased the amount of the unique tropoelastin mRNA. Hairless mouse skin (normal and UV treated) expressed the primary tropoelastin transcript although UV irradiation increased the length of its poly (A) tail two-fold. Therefore, UV radiation may stimulate elastin production by affecting polyadenylation site selection and the poly (A) tail length of tropoelastin mRNA.

Aged↗

Effect of UV-B phototherapy on plasma HIV type 1 RNA viral level: a self-controlled prospective study.

OBJECTIVE: To study the plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 12 patients seropositive for HIV who were undergoing UV-B phototherapy to determine if UV-B phototherapy upregulates HIV activity in humans. DESIGN: A self-controlled prospective cohort of HIV-infected patients seen for the treatment of a skin disorder responsive to UV-B phototherapy. Viral levels were measured weekly for 8 weeks of phototherapy. Follow-up viral levels were measured for patients who continued phototherapy beyond 8 weeks, those who had a significant change in their viral level, or both. SETTING: Outpatient clinic of an academic hospital. PATIENTS: Patients with HIV disease and a skin disorder responsive to UV-B phototherapy. Inclusion criteria for patients in this study were those receiving a stable antiviral regimen for at least 6 weeks and who had no major illness or immunization in the 2 months before starting phototherapy. Of 72 patient volunteers screened, 15 met the criteria, 2 declined to participate, and 13 entered the study. One patient was dropped from the study because an accurate baseline measurement could not be obtained. Twelve patients were analyzed, 2 of whom left the study early, 1 at 6 weeks and 1 at 7 weeks. INTERVENTIONS: Ultraviolet-B phototherapy. MAIN OUTCOME MEASURE: Plasma HIV-1 RNA viral level. RESULTS: Plasma HIV-1 RNA levels showed no significant increase or decrease in most of the patients, defined as a 3-fold change from baseline (mean fold change from baseline after 8 weeks of phototherapy, -1.1; 95% confidence interval, 2.9 to -5.0). Trend analysis indicated no significant pattern of change in viral levels (slope, -0.013 log; P > .25). The CD4+ cell counts also remained unchanged (mean before therapy, 277 x 10(9)/L; mean after therapy, 285 x 10(9)/L; P = .67). CONCLUSION: No significant effect of UV-B exposure was seen on plasma HIV-1 levels.

Adult↗

Determinants of compliance with anticoagulation: A case-control study.

BACKGROUND: The number of patients for whom long-term anticoagulation is indicated has increased dramatically over the past decade. Good patient compliance is necessary to safely realize the benefits of anticoagulation, yet barriers to compliance with anticoagulation therapy have not been studied. METHODS: We conducted a case-control study in the Anticoagulation Therapy Unit (ATU) at Massachusetts General Hospital. Forty-three patients who had been discharged from the ATU for noncompliance (cases) and 89 randomly selected compliant ATU controls were interviewed. Noncompliant cases had self-discontinued warfarin or were taking warfarin with inadequate monitoring of international normalized ratio (INR) levels. Telephone interviews assessed sociodemographic features, indication for anticoagulation, patient satisfaction, and health beliefs. RESULTS: Noncompliant cases were more likely to be younger (mean 53.7 years versus 68.7 years, P < 0.0001), male (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.5, 8.2) and nonwhite (OR 6.4, 95% CI 1.9, 21.9), and less likely to have had a stroke or transient ischemic attack (OR 0.2, 95% CI 0.1, 0.7). In open-ended questioning, cases were more likely to report that they did not know why warfarin had been prescribed (OR 4.4, 95% CI 1.4, 14.2). Noncompliant cases were more likely not to have a regular physician (OR 11.1, 95% CI 3.6, 50.0); among patients with a regular physician, noncompliant cases were more likely to feel dissatisfied. Examination of health beliefs revealed that noncompliant cases felt more burdened by taking warfarin, and perceived fewer health benefits. CONCLUSIONS: Patients who are noncompliant with warfarin share distinctive clinical characteristics. Notably, younger, male patients who have not experienced a thromboembolic event are more likely to forego INR testing or to stop anticoagulation therapy completely. Improved patient education, physician involvement, and ease of monitoring may improve compliance, particularly among younger male patients.

Adult↗

Stimulated rat mast cells generate histamine-releasing peptide from albumin.

Media conditioned by compound 48/80-stimulated rat mast cells generated immunoreactive histamine-releasing peptide (HRP) when incubated at physiological pH with bovine serum albumin and the carboxypeptidase inhibitor, O-phenanthroline. The generation of immunoreactive HRP (IR-HRP) was time (after 3 h the concentration of IR-HRP was 20 nM), temperature, and pH dependent and was prevented by omitting albumin, by using media conditioned by nonstimulated mast cells, or by pretreatment of mast cells with disodium cromoglycate, an inhibitor of mast cell secretion. The amount of IR-HRP generated increased linearly with the number of mast cells stimulated and varied directly with the concentration of conditioned media. After removal of the media from stimulated mast cells, the remaining cell pellet retained its ability to generate IR-HRP for up to 8 h. Stimulation of mast cells by either neurotensin or substance P, or of sensitized cells by anti-IgE serum, also produced conditioned media that generated IR-HRP. The amount of IR-HRP formed by various conditioned media or by stimulated cell pellets was dependent upon the concentration of O-phenanthroline used. Including the chymase inhibitor, chymostatin, prevented the formation of IR-HRP in a dose-dependent manner. HPLC analysis showed four peaks of IR-HRP. The major one coeluted with synthetic HRP. These results indicate that the peptide, HRP, can be generated by stimulated mast cells incubated in the presence of albumin. They suggest that a chymase-like enzyme secreted by the mast cell is able to cleave albumin to yield HRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Evaluation and treatment of itching in HIV-infected patients.

Itching is a common complaint among patients infected with HIV and may cause significant morbidity and embarrassment. Although idiopathic HIV-pruritus has been described, it is probably less common than was previously thought. In most patients, a careful history and physical examination will show that a dermatosis accounts for their pruritus. Dry skin, seborrheic dermatitis, eczema, psoriasis, pruritic papular eruption, staphylococcal folliculitis and prurigo nodularis are frequently encountered in these patients. These common dermatoses, drug eruptions, several rarer conditions and systemic causes of itching should be excluded before diagnosing idiopathic HIV-pruritus. Treatment should be directed to the underlying skin problem and may be supplemented with sedating antihistamines. Phototherapy is a safe and effective therapeutic modality for many pruritic dermatoses as well as for idiopathic pruritus.

AIDS-Related Opportunistic Infections↗