Biomedical subjects
Publications and source records attributed to T M Johnson.
Metastatic melanoma to the gastrointestinal tract is not uncommon with the small intestine representing the most common site of gastrointestinal metastases. The occurrence of primary melanoma of the small intestine, however, is rare. We describe a case of primary melanoma of the small intestine and establish criteria for distinction between primary and metastatic small intestinal melanoma.
We report a case of extragenital bowenoid papulosis (BP) in a healthy immunocompetent 42-year-old man. The lesions occurred on the anterolateral aspects of the neck and were not associated with genital, oral, or periungual lesions. Lesional skin tested positive with the Digene hybrid capture system cocktail assay that identifies infection with a mixture of high to intermediate oncogenic human papillomavirus (HPV) types, including types 16, 18, 31, 33, 35, 45, 51, 52, and 56. This cocktail assay identifies infection with HPV types typically associated with high-grade squamous intraepithelial lesions and invasive carcinoma. This case represents the sixth case of isolated cutaneous BP occurring a significant distance from the genital region.
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Direct intralesional injection of DNA encoding interferon-alpha2 (IFN-alpha2) was used in an effort to sustain local protein delivery for the treatment of human basal cell carcinoma (BCC). A novel model to study this malignancy was established by transplantation of human BCC tissue on to immunodeficient mice with a relatively high rate of engraftment and stable phenotype for superficial BCC (20 of 25; 80%). Gene transfer was significantly increased by using DNA liposome complexes (lipoplexes). Recombinant gene expression was detected predominantly in the epidermis and, to a lesser extent, in the dermis. Gene transfer of IFN-alpha2 using this method resulted in sustained production of IFN-alpha2 protein and increased expression of a known IFN-inducible gene, the class II major histocompatibility (MHC) antigen, and induced BCC regression, presumably through a non-immune mechanism. Intralesional injection of DNA lipoplexes encoding IFN-alpha protein may therefore be applicable to the treatment of cutaneous BCC.
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Measurements of the tissue concentrations of two chemotherapy agents have been made in vivo on an animal tumour model. The method used is based on elastic scattering spectroscopy (ESS) and utilizes a fibre-optic probe spectroscopic system. A broadband light source is used to acquire data over a broad range of wavelengths and, therefore, to facilitate the separation of absorptions from various chromophores. The results of the work include measurements of the time course of the drug concentrations as well as a comparison of the optical measurements with high performance liquid chromatography (HPLC) analysis of the drug concentrations at the time of sacrifice. It is found that the optical measurements correlate linearly with HPLC measurements, but give lower absolute values.
Interferon-tau (IFN-tau) is a novel type I IFN that was originally identified as a pregnancy recognition hormone. IFN-tau shares all of the biological properties of other type I IFNs including antiviral activity and antiproliferative activity through induction of the cell cycle inhibitor gene product p21WAF1. It is a promising therapy for cancers, viral infections, and for autoimmune disorders such as multiple sclerosis, without the adverse side effects associated with IFN-alpha and IFN-beta. Here, we describe novel growth and induction conditions for the expression of functionally active and uniformly 15N-labeled IFN-tau from Pichia pastoris in a minimal media for use in initial 2D- and 3D-NMR studies in solution. Purified 15N-IFN-tau was homogenous, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and MALDI-TOF mass spectrometer (MS), and retained full biological activity. MS analysis confirmed uniform isotopic labeling of IFN-tau with 15N incorporation exceeding 99%. Circular dichroism (CD) as well as 1D-NMR and 15N-1H heteronuclear single quantum coherence (HSQC) spectra confirmed that purified 15N-labeled IFN-tau has a stable secondary structure. Besides providing a route for isotope labeling of IFN-tau, our procedure may be useful for the expression and purification of other proteins that are difficult to obtain in Pichia pastoris grown in minimal media.
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BACKGROUND: The objective of this study was to determine whether there are intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells from a multistep carcinogenesis model. METHODS: Wavelength-dependent and polarization-dependent light scattering properties of cell suspensions were measured. RESULTS: Statistically significant differences were found between the tumorigenic and nontumorigenic cells. CONCLUSIONS. Differences in the light scattering properties of tumorigenic and nontumorigenic cells are attributed to a change in the average size of the scattering centers on the order of a few ten of nanometers. This work is relevant to the development of noninvasive optical methods for cancer diagnosis.
Normal as well as neoplastic cells traverse extracellular matrix barriers by mobilizing proteolytic enzymes in response to epidermal growth factor (EGF)-EGF receptor (EGFR) or hepatocyte growth factor/scatter factor (SF)-c-Met interactions. The plasminogen activator-plasminogen axis has been proposed to play a key role during cell invasion, but the normal development of plasminogen activator- as well as that of plasminogen-deficient mice supports the existence of alternate proteolytic systems that permit cells to traverse extracellular matrix barriers. To characterize the role that matrix-degrading proteinases play in EGF- or SF-stimulated invasion, a human squamous carcinoma cell line (UM-SCC-1) was triggered atop the matrices of type I collagen or human dermal explants in a three-dimensional culture system. During EGF- or SF-induced invasion, UM-SCC-1 cells expressed urokinase-type plasminogen activator (uPA) and uPA receptor as well as the matrix metalloproteinases (MMPs), membrane-type MMP-1, collagenase 1, stromelysin 1, and gelatinase B. Despite the presence of a positive correlation between uPA receptor-uPA expression and growth factor-stimulated invasion, UM-SCC-1 invasion was not affected by inhibitors directed against the plasminogen activator-plasminogen axis. In contrast, both recombinant and synthetic MMP inhibitors completely suppressed invasion by either EGF- or SF-stimulated cells without affecting either proteinase expression or cell motility across collagen-coated surfaces. These data demonstrate that MMPs, but not the plasminogen activator-plasmin system, can directly regulate the ability of either EGF- or SF-stimulated tumor cells to invade interstitial matrix barriers.
OBJECTIVE: To evaluate the use of an initial staging chest x-ray film in asymptomatic patients who present with localized primary cutaneous melanoma. DESIGN: The staging workup of 1032 consecutive asymptomatic patients with localized melanoma was retrospectively reviewed via database chart review. SETTING: Regional melanoma referral center in an academic medical center. PATIENTS: The melanoma database identified 1032 asymptomatic patients with localized melanoma for retrospective review. Of the patients studied, 876 (85%) of 1032 had an initial staging chest x-ray film performed. A chest x-ray film was considered initial if performed within 6 months of melanoma diagnosis. MAIN OUTCOME MEASURE: The rate of positive, negative, and suspicious findings of initial chest x-ray films. RESULTS: One hundred thirty (15%) of 876 patients had suspicious findings necessitating additional workup. Based on follow-up radiologic findings, only 1 (0.1%) of 876 had a true-positive chest x-ray film demonstrating pulmonary metastasis. CONCLUSIONS: The yield of detection of unsuspected pulmonary metastasis by chest x-ray film in the initial evaluation of asymptomatic patients with localized melanoma was exceedingly low (0.1%). Our results support the concept that routine chest radiograph screening in asymptomatic patients presenting with stage I and intermediate-thickness (1.5- to 4.0-mm) stage II melanoma is unlikely to yield true-positive findings of silent pulmonary metastasis. No definitive conclusions were drawn for the subset of patients with stage II thick melanoma (> 4.0 mm) because of the small number of patients (n = 40) in our series. Prospective studies are necessary to ultimately define the yield of initial radiographs in asymptomatic patients with localized melanoma.
OBJECTIVE: To review and report our experience with the subcutaneous pedicle flap in the reconstruction of defects adjacent to the melolabial crease. DESIGN: Retrospective review. SETTING: Cutaneous surgery unit of an academic tertiary referral center. PATIENTS: One hundred nine patients with defects of the lateral aspect of the upper lip, the medial aspect of the cheek, and the melolabial crease after Moh excision of cutaneous lesions. CONCLUSIONS: In our experience, the subcutaneous pedicle advancement flap is often ideally suited to the reconstruction of cutaneous defects adjacent to the melolabial crease. We have been particularly satisfied with the results of this reconstructive technique when addressing deep defects adjoining the alar facial sulcus in patients with full cheeks.
BACKGROUND: Several changing clinical and histopathologic melanoma trends occurred from the 1950s to the 1980s. OBJECTIVE: The purpose of this study was to evaluate melanoma trends during the past decade and to compare present trends to those documented during the past four decades. METHODS: Sex, age at diagnosis, location, tumor thickness, stage, and histologic subtypes were evaluated from 1984 to 1995 and compared with trends during the past four decades. RESULTS: Most changing trends from the past four decades have slowed or stabilized during the past decade. CONCLUSION: Complete reporting of all melanomas to central tumor registries is necessary to accurately analyze present and future melanoma trends. Ongoing and new prevention and control strategies beginning at birth may be necessary to continue the positive efforts to curtail the melanoma epidemic.
This review discusses several advances in melanoma therapy that have recently occurred or are presently in a developmental stage. We discuss the history and present dogma regarding assessment of the regional lymph nodes and adjuvant therapy for melanoma. Of special interest is radiolymphatic sentinel node mapping of the lymph nodes and adjuvant interferon alfa-2b for thick primary lesions and stage III disease. We also discuss several evolving novel and innovative genetic immunotherapy approaches for patients with stage IV disease.
The traditional process of melanoma care delivery can differ substantially among providers regarding screening laboratories, staging work-ups, surgical margins, and outpatient versus inpatient surgical management. It has been suggested that multidisciplinary care may provide a more cost-effective management approach. We sought to evaluate whether coordinated multidisciplinary melanoma care that follows evidence-based, consensus-approved clinical practice guidelines at a large academic medical center can provide a more efficient alternative to traditional community-based strategies with clinical outcomes that are at least equivalent. The University of Michigan Multidisciplinary Melanoma Clinic (MDMC) possesses a database of demographic, clinical, and treatment information for all patients seen since its inception. A consecutive sample of 104 patients with local disease who were treated in the Michigan community were compared with 104 blindly selected subjects treated at the MDMC during an identical time period, matched for Breslow depth and melanoma body site. Patients treated in the MDMC would save a third party payer roughly $1600 per patient when compared with a similar group treated in the Michigan community. Surgical morbidity, length of hospitalization, and long-term survival of MDMC patients were similar to those reported in the literature. The cost discrepancy is explained by the fundamental differences in the usage pattern of health care resources exhibited by the MDMC compared with the community setting.
BACKGROUND: The diagnosis of primary melanoma increases the risk of additional primary melanomas. OBJECTIVE: We characterize the subgroup of patients with multiple melanomas. METHODS: We reviewed the melanoma database. RESULTS: Sixty patients with multiple primary melanomas were identified. Twelve (20%) experienced melanomas in the same regional location, 43 (72%) in different locations, and 5 (8%) in both the same and different locations (> 2 melanomas). Eighteen (30%) were diagnosed concurrently with multiple melanomas, 38 (63%) subsequently, and 4 (7%) concurrently and subsequently (>2 melanomas). Forty-two percent of subsequent melanomas occurred within 3 years of the initial lesion diagnosis, 9 (17%) between 3 and 7 years, and 22 (42%) after more than 7 years. Subsequent melanomas were thinner in 70% of cases (P = .05). The mean age at first melanoma diagnosis was 38 and 59 years, respectively, for those with and without dysplastic nevi (P < .001). CONCLUSION: In patients with multiple melanomas, subsequent melanomas often occur in different regional locations several years after diagnosis of the initial lesion.
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BACKGROUND: Complete spontaneous regression of melanoma metastatic to the lungs is a rare event. OBJECTIVE: To report a case of biopsy-proven melanoma metastatic to the lung with complete spontaneous regression. METHODS: Multidisciplinary case report. RESULTS: A 35-year-old white female was diagnosed with metastatic melanoma to the lung. A pleural biopsy confirmed the diagnosis. Partial spontaneous regression was noted by a staging computed tomography scan prior to enrollment in an investigational protocol. Complete spontaneous regression occurred over 5 months without any form of conventional or alternative therapy, and the patient remains disease-free 3 years after diagnosis. CONCLUSIONS: Our case represents the seventh case of complete spontaneous regression of melanoma metastatic to the lung, and the only case with histologic confirmation of both the primary and pulmonary metastatic lesions. The patient was pregnant twice between the time of her initial diagnosis of primary melanoma and pulmonary metastatic disease.