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Biomedical subjects

Michael B Morgan

Publications and source records attributed to Michael B Morgan.

At least 37 records · Page 2Linked to original sources
PubMed2004

A reappraisal of the histologic findings of pigmented pretibial patches of diabetes mellitus.

BACKGROUND: Pigmented pretibial patches (PPPs) are the most common cutaneous alterations in diabetes mellitus, found in up to 50% of diabetic patients. They classically present as flat-topped, dull-red papules on the pretibial areas, later becoming hyperpigmented and atrophic. Little is known regarding the pathogenesis of these lesions, and the histopathologic findings have been regarded as non-specific. METHODS: We investigated the clinical and pathologic attributes of a series of 12 diabetic patients with PPP in an effort to discern any specific histologic attributes compared to normal skin removed from diabetic patients with cutaneous carcinoma. RESULTS: All cases of PPP showed hyaline microangiopathy, all patients showed extravasated erythrocytes and/or hemosiderin deposits, and 10 patients showed an appreciable number of perivascular plasma cells. The average number of plasma cells per vascular plexus was 2.2. Control specimens removed from five diabetic patients showed hyaline microangiopathy, and three showed extravasated erythrocytes and hemosiderin. One patient showed a single vascular plexus with two plasma cells, p = 0.01. CONCLUSION: The presence of increased dermal perivascular plasma cells in the appropriate clinical context might be an important and under-recognized clue for PPP. The pathogenic significance of this finding is unknown.

Adult↗
PubMed2004

Merkel cell carcinoma: a clinicopathologic study with prognostic implications.

BACKGROUND: Merkel cell carcinoma (MCC) is a frequently aggressive neuroendocrine malignancy of the skin that presents in sun-exposed areas on elderly patients. Although originally described over 30 years ago, many aspects of MCC remain to be defined. Of particular importance is the need to identify prognostic factors capable of predicting the biological behavior of these tumors. Knowledge of these factors may help in determining which patients require more aggressive treatment regimens. In this study, we examined 25 cases of MCC with an attempt to identify clinical, histopathological, or immunohistochemical features capable of predicting disease outcome. METHODS: Features that we evaluated in each case included age, gender, race, tumor location, tumor size, depth of invasion, growth pattern, lymphocytic infiltration, mitotic activity, ulceration, necrosis, vascular invasion, and perineural invasion. In addition, we examined neural cell adhesion molecule and cytokeratin-20 expression using immunohistochemical methods. RESULTS: We found that most patients were males (84%) with an average age of 74 years. The tumors were located on the head and neck (68%) and upper extremities (32%). Overall, 64% of the patients developed metastatic disease to regional lymph nodes or distant sites (average follow-up time of 21 months). Local recurrence was also common, occurring in 29% of the patients. The overall 1- and 2-year survival rates were 80 and 53%, respectively. Histopathological examination revealed tumors with an average size of 7.2 mm. Common features included invasion into the subcutaneous adipose tissue, solid growth pattern, tumor necrosis, and vascular and perineural invasion. Findings that had a statistically significant correlation with poor outcome included tumor size > or =5 mm (p = 0.047), invasion into the subcutaneous adipose tissue (p = 0.005), diffuse growth pattern (p = 0.040), and heavy lymphocytic infiltration (p = 0.017). The remaining findings, including the immunohistochemical results, did not correlate with disease outcome. Using logistic regression models, we show that depth of invasion and degree of lymphocytic infiltration are strong predictors of disease outcome. CONCLUSIONS: The current controversies regarding the treatment of early-stage MCC (i.e., localized disease) underscore the importance of identifying clinicopathological features capable of predicting tumor behavior. In this study, we have identified several prognostic features in MCC. Perhaps, these features may prove useful in identifying patients who require more aggressive treatment regimens.

Aged↗
PubMed2004

Expression of insulin-like growth factor-I receptor in primary cutaneous carcinomas.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is the principal mediator of growth hormone, exerting its effects through binding of the insulin-like growth factor-I receptor (IGF-IR). Post-receptor activation leads to the production of transcription factors involved in cell proliferation, differentiation, transformation, and survival. Data indicate that IGF-IR is involved in tumorigenesis. To our knowledge, this receptor has not been previously studied in primary cutaneous carcinomas. METHODS: Twenty-five cases of primary cutaneous carcinomas consisting of three keratoacanthoma-type squamous cell carcinomas (KAs), two squamous cell carcinomas in situ (SCCs in situ), eight squamous cell carcinomas (SCCs), three conventional basal cell carcinomas (BCCs), two morpheaform basal cell carcinomas (M-BCCs), and seven Merkel cell carcinomas (MCCs) were analyzed for IGF-IR immunohistochemical expression using IGF-IR mouse monoclonal antibody (dilution 1 : 50) using the avidin-biotin-peroxidase complex method. RESULTS: Normal epidermis was negative for IGF-IR expression. Normal eccrine glands and outer root sheath strongly expressed IGF-IR. All KAs, SCCs in situ, SCCs, and BCCs were negative for IGF-IR expression. Six of seven (86%) of the MCCs stained with IGF-IR strongly, showing cell membrane accentuation and a perinuclear dot-like pattern. CONCLUSION: The data suggest that IGF-IR immunopositivity in MCCs might constitute a diagnostic tool in discriminating between SCCs and BCCs. Although the possible pathogenic significance of the perinuclear dot-like staining pattern observed in these neoplasms is unknown, its pattern is similar to what has been previously described with cytokeratin-20 immunostaining.

Antibodies, Monoclonal↗
PubMed2004

Hamartin and tuberin immunohistochemical expression in cutaneous fibroepithelial polyps.

BACKGROUND: Hamartin and tuberin are inactivating tumor suppressor proteins implicated in the development of gastrointestinal polyps and sporadic and tuberous sclerosis-associated cutaneous angiofibromas. The pattern of expression of these peptides has not been studied in fibroepithelial polyps (FEPs). DESIGN: The specific aim of the study was to evaluate the immunohistochemical expression of tuberin and hamartin within the epithelium and dermal fibrocytes of 20 cutaneous FEPs compared with the epithelium and dermal fibrocytes of normal skin. The diagnoses were confirmed independently by a dermatopathologist, and the pattern of intensity was assessed by the mean labeling intensity (MLI) of cytoplasmic and/or nuclear staining for each antibody. RESULTS: Hamartin and tuberin antibodies showed moderate staining of the keratinocytes and fibrocytes of normal skin and the keratinocytes within FEPs. Both antibodies showed diminished staining within the fibrocytes of the FEPs. The MLI of hamartin was 44.3 +/- 4.4 for keratinocyte nuclei in normal skin and 51.2 +/- 3.7 within the polyps. The MLI of tuberin was 42.9 +/- 3.6 within the keratinocyte nuclei of the normal skin compared to 39.7 +/- 3.0 for the polyps. The MLI for hamartin within the fibrocytes of the normal skin was 78.9 +/- 7.1 compared to 21.6 +/- 4.2 within the polyps, p = 0.01. The MLI for tuberin within the fibrocytes of normal skin was 70.6 +/- 5.0 compared to 47.1 +/- 4.7 within the polyps. CONCLUSION: The data suggest that down regulation or loss of tuberin and/or hamartin expression may be permissive to fibrocyte proliferation or promote collagen production leading to FEP formation.

Case-Control Studies↗
PubMed2004

Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal.

BACKGROUND: Cutaneous tumor metastasis may be the first manifestation of cancer, but more often is a harbinger of advanced disease that portends an ominous prognosis. All skin accessions over the past 10 years from a large Veterans Administration (VA) hospital were reviewed. METHODS: Archived histories, glass slides, and the immunohistochemical battery (IHC), were assessed to determine diagnostic accuracy. RESULTS: Of the 100,453 cases reviewed, there were a total of 77 cases (75 males and 2 females) of cutaneous metastasis from the lungs (28.6%), metastatic melanoma (18.2%), gastrointestinal tract (14.2%), genitourinary tract (10.4%), head and neck (9.1%), hematologic (5.2%), breast (5.2%), and miscellaneous (<2%). Metastasis represented the first indication of an internal malignancy in 7.8% of cases. The cutaneous sites of involvement included the head and neck (28%), the trunk (40%), the extremities (18%), and multiple sites (14%). The age range was 38-83 years, with a mean of 62 years. The average time interval between diagnosis of internal malignancy and cutaneous presentation was 33 months (range: <1 month-22 years), and the average survival following diagnosis was 7.5 months (range: <1 month-8 years). In a cohort of subjects, a truncated immunohistochemical battery consisting of CK-7, CK-20, and S-100 was consistent with the expected staining pattern of the primary source of cutaneous metastasis in 83.33% of the patients. CONCLUSIONS: Excluding the potential for age and gender bias in this study conducted in a VA setting, cutaneous metastases represent an uncommon, deadly, and late-developing occurrence in many patients. Compared with previous studies, lung carcinoma remains the most common of the cutaneous metastases, with a relative rise in the incidence of metastatic melanoma. The immunohistochemical battery of CK-7, CK-20, and S-100 is a helpful adjunct in narrowing the differential diagnosis of the primary site of a large proportion of cutaneous metastases, particularly tumors with an epithelioid appearance such as carcinomas and melanomas.

Adult↗
PubMed2004

Human umbilical cord blood mononuclear cells for the treatment of acute myocardial infarction.

Cell transplantation is a new treatment to improve cardiac function in hearts that have been damaged by myocardial infarction. We have investigated the use of human umbilical cord blood mononuclear progenitor cells (HUCBC) for the treatment of acute myocardial infarction. The control group consisted of 24 normal rats with no interventions. The infarct + vehicle group consisted of 33 rats that underwent left anterior descending coronary artery (LAD) ligation and after 1 h were given Isolyte in the border of the infarction. The infarct + HUCBC group consisted of 38 rats that underwent LAD ligation and after 1 h were given 10(6) HUCBC in Isolyte directly into the infarct border. Immunosuppression was not given to any rat. Measurements of left ventricular (LV) ejection fraction, LV pressure, dP/dt, and infarct size were determined at baseline and 1, 2, 3, and 4 months. The ejection fraction in the controls decreased from 88+/-3% to 78+/-4% at 4 months (p = 0.03) as a result of normal aging. Following infarction in the infarct + vehicle group, the ejection fraction decreased from 87+/-4% to 51+/-3% between 1 and 4 months (p < 0.01). In contrast, the ejection fraction of the infarcted + HUCBC-treated rat hearts decreased from 87+/-4% to 63+/-3% at 1 month, but progressively increased to 69+/-6% at 3 and 4 months, which was different from infarct + vehicle group rats (p < 0.02) but similar to the controls. At 4 months, anteroseptal wall thickening in infarct + HUCBC group was 57.9+/-11.6%, which was nearly identical to the control anteroseptal thickening of 59.2+/-8.9%, but was significantly greater than the infarct + vehicle group, which was 27.8+/-7% (p < 0.02). dP/dt(max) increased by 130% in controls with 5.0 microg of phenylephrine (PE)/min (p < 0.001). In the infarct + vehicle group, dP/dt(max) increased by 91% with PE (p = 0.01). In contrast, in the infarct + HUCBC group, dP/dt(max) increased with PE by 182% (p < 0.001), which was significantly greater than the increase in dP/dt(max) in the infarct + vehicle group (p = 0.03) and similar to the increase in the controls. Infarct sizes in the infarct + HUCBC group were smaller than the infarct + vehicle group and averaged 3.0+/-2.8% for the infarct + HUCBC group versus 22.1+/-5.6% for infarct + vehicle group at 3 months (p < 0.01); at 4 months they averaged 9.2+/-2.0% for infarct + HUCBC group versus 40.0+/-9.2% for the infarct + vehicle group (p < 0.001). The present experiments demonstrate that HUCBC substantially reduce infarction size in rats without requirements for immunosuppression. As a consequence, LV function measurements, determined by LV ejection fraction, wall thickening, and dP/dt, are significantly greater than the same measurements in rats with untreated infarctions.

Acute Disease↗
PubMed2003

Telepathology in the diagnosis of routine dermatopathologic entities.

BACKGROUND: Telepathology involves the use of video technology to facilitate remote-site diagnosis. To our knowledge, no studies have compared the reproducibility of real-time telepathology between dermatopathologists with that of traditional 2-headed microscopy in the diagnoses of routine dermatopathologic entities. OBSERVATIONS: The kappa statistic for both techniques was favorable: 0.76 (telepathology) vs 0.93 (conventional 2-headed microscopy); P =.04. The time taken per case was 42 seconds (telepathology) vs19 seconds (conventional 2 -headed microscopy); P =.003. CONCLUSIONS: Telepathology between 2 remote diagnostic centers offers a feasible means of facilitating the remote-site diagnosis of routine dermatopathologic entities. Although diagnostic accuracy and time taken per case were acceptable with video-assisted diagnosis, conventional microscopy had significantly higher accuracy and shorter time per diagnosis.

Computer Systems↗
PubMed2003

Gene expression profiling in ecotoxicology.

Gene expression profiling is a powerful new end point for ecotoxicology and a means for bringing the genomics revolution to this field. We review the usefulness of gene expression profiling as an end point in ecotoxicology and describe methods for applying this approach to non-model organisms. Since genomes contain thousands of genes representing hundreds of pathways, it is possible to identify toxicant-specific responses from this wide array of possibilities. Stressor-specific signatures in gene expression profiles can be used to diagnose which stressors are impacting populations in the field. Screening for stress-induced genes requires special techniques in organisms without sequenced genomes. These techniques include differential display polymerase chain reaction (DD PCR), suppressive subtractive hybridization PCR (SSH PCR), and representational difference analysis. Gene expression profiling in model organisms like yeast has identified hundreds of genes that are up-regulated in response to various stressors, including several that are well characterized (e.g., hsp78, metallothionein, superoxide dismutase). Using consensus PCR primers from several animal sequences, it is possible to amplify some of these well characterized stress-induced genes from organisms of interest in ecotoxicology. We describe how several stress-induced genes can be grouped into cDNA arrays for rapidly screening samples.

Animals↗
PubMed2003

Multiple follicular cysts, infundibular type with vellus hairs and solar elastosis of the ears: a new dermatoheliosis?

BACKGROUND: Vellus hair cyst is an uncommon developmental abnormality of the vellus follicle histologically defined as a stratified squamous epithelial-lined cyst containing one or more vellus hairs. METHODS: Herein, we report three patients with a heretofore described clinicopathologic condition consisting of multiple contiguous cysts of the ear helices showing solar elastosis and multiple cysts containing vellus hairs, microscopically. CONCLUSION: Given the anatomic location, history of excessive ultraviolet exposure and pathologic alterations, we surmise that this is a condition related to Favre-Racouchot syndrome, which is predisposed by excessive ultraviolet light exposure.

Aged↗
PubMed2003

Localized amyloidosis of the glans penis: a case report and literature review.

BACKGROUND: Primary localized cutaneous amyloidosis is an uncommon lesion with a varied pathogenesis. METHODS: We report the case of a 67-year-old-male discovered to have a localized amyloid lesion of the glans penis. RESULTS: Biopsy of the lesion revealed dermal deposits of amorphous eosinophilic material which stained positive with Congo red and amyloid P protein. Additional stains, including kappa and lambda light chains, amyloid A, and transthyretin, were negative. The lesion has remained asymptomatic, with no evidence of systemic disease identified, and no further treatment has been necessary. CONCLUSIONS: This is the sixth reported case of localized amyloidosis of the glans penis. Based on the clinical behavior and pathologic characteristics, this type of lesion is best classified as primary localized cutaneous amyloidosis, in the same family as the macular/lichenoid type lesions.

Aged↗
PubMed2003

Littoral cell angiomatosis with poorly differentiated adenocarcinoma of the lung.

We report on a 64-year-old male United States Navy Veteran of World War II, one of two identical twins, diagnosed with littoral cell angiomatosis of the spleen, liver, and lymph nodes, later found to have a massive poorly differentiated adenocarcinoma involving the mediastinum, adjoining lung, and sternum with widespread metastases. Herein we include our findings at autopsy, pertinent immunohistochemical studies, and a review of the literature pertaining to littoral cell angiomatosis with comment on its association with visceral malignancies.

Adenocarcinoma↗
PubMed2003

Diagnostic pitfalls: case report of scurvy in a man with spinal cord injury.

BACKGROUND: A 49-year-old man with spinal cord injury (SCI) developed a progressive purpuric rash and painful swelling of the lower extremities, in addition to chronic purpura over the ischial tuberosities. DESIGN: Case report. FINDINGS: Following an extensive workup for presumed vasculitis, a skin biopsy showed evidence of scurvy. Risk factors for scurvy included limited means of transportation, living alone, and alcohol abuse. CONCLUSIONS: Scurvy can be confused with disorders common among SCI patients, such as vasculitis, venous thrombosis, occult trauma, and pressure injury. Scurvy should be considered in the differential diagnosis of skin lesions, especially in individuals who abuse alcohol and live alone.

Diagnosis, Differential↗
PubMed2003

Lymphoid lost and found.

We present the clinicopathologic features of a case initially interpreted as lymphocytoma cutis that was later determined to be lymphoepithelioma-like carcinoma of the skin. The histologic presence of nodular aggregates of undifferentiated epithelioid cells surrounded by a dense, reactive lymphocytic infiltrate should prompt consideration of the diagnosis of lymphoepithelioma-like carcinoma of the skin. This lesion should be distinguished from lymphocytoma cutis, B-cell lymphoma, and cutaneous lymphadenoma.

Aged↗
PubMed2003

Expression of the ets-1 proto-oncogene in melanocytic lesions.

Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in melanocytic lesions. A series of 10 cutaneous melanomas and 24 benign melanocytic lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle upon Tyne, UK) was scored by an average of the mean labeling intensity; no nuclear staining = 0, weak nuclear staining = 1, moderate = 2, and intense = 3. Ets-1 expression was statistically assessed by the one-way analysis of variance (ANOVA) comparing the mean labeling intensity of melanoma to benign melanocytic nevi. All of the benign melanocytic lesions exhibited negative to weak nuclear staining, with an average mean labeling intensity of 0.4. Melanoma in situ exhibited moderate nuclear staining, for a mean labeling intensity of 2.0, whereas all conventional invasive melanomas exhibited moderate to strong nuclear staining, with a mean labeling intensity of 2.7. Metastatic melanoma exhibited very strong nuclear staining, with a mean labeling intensity of 3.0. Invasive desmoplastic melanoma, like melanoma in situ, showed moderate nuclear staining with a mean labeling intensity of 2.1. There was a trend toward more intense staining with melanoma progression. A statistically significant difference in the mean labeling intensity of Ets-1 was seen between invasive melanoma and benign melanocytic nevi (P <.0001). Ets-1 oncoprotein expression, however, does not distinguish among benign melanocytic lesions. Staining intensity and pattern might be a useful adjunct with histomorphology in distinguishing invasive melanoma from benign melanocytic nevi. Furthermore, Ets-1 expression may be an important pathogenic mechanism and predictor of aggressive biologic behavior of cutaneous melanoma, with a trend toward staining intensity increasing as Clark stage increases.

Biomarkers, Tumor↗
PubMed2003

An investigation of apoptosis in androgenetic alopecia.

While the androgens, including dihydrotestosterone (DHT), have been implicated in the development of androgenetic alopecia (AGA), the exact mechanism by which they exert their effect(s) is unknown. Since apoptosis is an integral component of the normal cycling of human hair, we investigated individuals clinically affected by AGA to assess whether objective differences in the expression of apoptosis-related immunohistochemical markers could be observed in scalp biopsies. Specimens from 16 alopecic male patients were stained with bd-2 and the terminal deoxynucleotidyltransferase dUTP fluorescein nick end-labeling (TUNEL) method was used to assess apoptotic activity in affected and unaffected areas ofthe scalp. Immunoreactivity was analyzed by quantifying staining differences within the same individual. Sections from 3 human volunteers were used to establish the method validity. Significant differences in the bcl-2 staining index (0.67 versus 0.42, p < 0.05) and TUNEL expression (5.7 versus 10.2, p < 0.05) were observed between the areas of the scalp that were clinically affected (frontal) and unaffected (occipital) by AGA. The Gaussian distributions of bcl-2 and TUNEL staining suggest that a relatively uniform population of follicles exists at the frontal hairline and/or that synchrony of follicular cycling occurs in AGA. The apoptosis "hot spot" revealed by TUNEL staining in the bulge-isthmus region of the murine follicle is also identifiable in the human follicle.

Alopecia↗