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Biomedical subjects

J L Messina

Publications and source records attributed to J L Messina.

At least 19 recordsLinked to original sources

Proliferating trichilemmal cysts of the scalp on CT.

Proliferating trichilemmal cysts, also known as pilar tumors, are slow-growing lobulated masses most commonly found on the scalp of elderly women. We present the case of a 69-year-old woman with a 25-year history of multiple enlarging scalp masses. The patient was evaluated for surgical consultation after the dominant mass presented with malignant degeneration. A CT of the head revealed multiple large, subcutaneous, cystic masses with calcifications.

Aged↗

Extrafacial granuloma faciale: report of a case and response to treatment.

Granuloma faciale (GF) is a rather uncommon form of chronic vasculitis that infrequently involves extrafacial sites. Treatment of this disease is extremely challenging. We report a case of GF with extrafacial lesions and a unique response to treatment. The diseases that are clinical and histologic mimics of this disorder, as well as a review of various treatment modalities, are discussed.

Dapsone↗

Differential expression of thyroid transcription factor 1 in small cell lung carcinoma and Merkel cell tumor.

The distinction between metastatic small cell lung carcinoma (SCLC) and Merkel cell tumor is difficult by routine histology, prompting the search for specific markers that could separate these neoplasms. Thyroid transcription factor 1 (TFF-1) is a homeodomain containing transcription factor expressed in the normal airway epithelium. The expression of TTF-1 has also been shown in adenocarcinomas and small cell carcinomas of the lung. However, the utility of TTF-1 to differentiate between SCLC and Merkel cell tumor has not yet been investigated. In this study, paraffin sections of 36 SCLCs and 21 Merkel cell tumors were analyzed for the presence of immunoreactive TTF-1 and cytokeratin 20 (CK20), a marker previously demonstrated in Merkel cell tumors. Monoclonal TTF-1 and CK20 antibodies were used with a biotin-streptavidin detection system. Immunostaining for TTF-1 was observed in 97% of SCLCs and in no Merkel cell tumors. Immunoreactivity for CK20 was demonstrated in 76% of Merkel cell tumors and 3% of SCLCs. These data indicate that TTF-1 is a sensitive (97%) and specific (100%) marker for SCLCs and can be used to differentiate SCLCs from Merkel cell tumors.

Carcinoma, Merkel Cell↗

Ileal perforation secondary to histoplasmosis in AIDS.

Our patient presented with abdominal pain, weight loss, and fever with evidence of oral thrush and pelvic inflammatory disease on exam. Radiographs demonstrated a small bowel obstruction with free air. An exploratory laparotomy demonstrated 2 perforations of the distal ileum. Pathologic exam revealed features consistent with histoplasmosis. We discuss gastrointestinal involvement of histoplasmosis in AIDS and its treatment.

Acquired Immunodeficiency Syndrome↗

Insulin inhibits growth hormone signaling via the growth hormone receptor/JAK2/STAT5B pathway.

Insulin is important for maintaining the responsiveness of the liver to growth hormone (GH). Insulin deficiency results in a decrease in liver GH receptor (GHR) expression, which can be reversed by insulin administration. In osteoblasts, continuous insulin treatment decreases the fraction of cellular GHR localized to the plasma membrane. Thus, it is not clear whether hyperinsulinemia results in an enhancement or inhibition of GH action. We asked whether continuous insulin stimulation, similar to what occurs in hyperinsulinemic states, results in GH resistance. Our present studies suggest that insulin treatment of hepatoma cells results in a time-dependent inhibition of acute GH-induced phosphorylation of STAT5B. Whereas total protein levels of JAK2 were not reduced after insulin pretreatment for 16 h, GH-induced JAK2 phosphorylation was inhibited. There was a concomitant decrease in GH binding and a reduction in immunoreactive GHR levels following pretreatment with insulin for 8-24 h. In summary, continuous insulin treatment in rat H4 hepatoma cells reduces GH binding, immunoreactive GHR, GH-induced phosphorylation of JAK2, and GH-induced tyrosine phosphorylation of STAT5B. These findings suggest that hepatic GH resistance may develop when a patient exhibits chronic hyperinsulinemia, a condition often observed in patients with obesity and in the early stage of Type 2 diabetes.

Animals↗

Persistent Sweet's syndrome occurring in a child with a primary immunodeficiency.

Sweet's syndrome (SS) occurs most commonly in association with inflammatory or neoplastic disorders. Only rarely has it been associated with immunodeficiency disorders. We describe a child with a T-cell immunodeficiency who had a persistent neutrophilic dermatosis that was histologically and clinically consistent with SS. SS associated with immunodeficiencies may occur as a reaction to an underlying infection or a defect in immunoregulation. Such patients, however, may not be able to produce the classic fever and neutrophilia associated with SS. They may fail to respond to standard treatment for SS and may suffer a prolonged and persistent course.

B-Lymphocytes↗

Pathologic examination of the sentinel lymph node in malignant melanoma.

Sentinel lymphadenectomy is gaining increasing popularity in the staging and treatment of patients with melanoma at risk for metastases. As a result, pathologists are encountering these specimens more frequently in their daily practice. The pathologic status of the sentinel lymph node is pivotal to the patient's care because it provides staging information that dictates the need for further therapy, and therefore detailed pathologic assessment is warranted. A standard pathology protocol to handle these nodes has been developed at our institution and involves complete submission of all tissue with routine use of immunohistochemical staining for S-100 protein. By using this protocol, 838 sentinel lymph nodes from 357 patients have been examined, and metastases were found in 16% of patients. Although the metastasis was clearly seen on sections stained with hematoxylin and eosin in 55% of the positive patients, the immunostain showed metastatic disease not appreciable on initial hematoxylin and eosin screening in an additional 28 lymph nodes (45% of node-positive patients). Intraoperative touch preparation cytology may be used as an adjunct technique in sentinel lymph nodes grossly suspicious for metastatic disease. This technique has been performed on 23 sentinel lymph nodes, with no false positives and an overall sensitivity of 62%. The thorough pathologic evaluation of sentinel lymph nodes in patients with malignant melanoma requires complete submission of all tissue, routine use of immunohistochemistry, and touch preparation cytology in selected cases.

False Positive Reactions↗

Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma of the lower extremity.

Lymphatic mapping and sentinel lymph node biopsy is a new technique used in the surgical treatment of patients with malignant melanoma. The purpose of this study was to evaluate the results of this approach for patients with melanoma of the lower extremity. Between May of 1994 and June of 1997 at the H. Lee Moffitt Cancer Center and Research Institute, 85 consecutive patients with clinical stage I and II melanoma of the lower extremity underwent lymphatic mapping and sentinel lymph node biopsy. These nodes were identified in all 85 patients by intraoperative lymphatic mapping with both radiolymphoscintigraphy and a vital blue dye injection. Eleven patients (12.9 percent) had histologically positive sentinel lymph nodes, and 10 patients underwent inguinal complete lymph node dissections. All 10 patients had no further histologically positive lymph nodes confirmed by subsequent complete dissection. Among 74 patients with histologically negative sentinel lymph nodes, only 2 patients (2.7 percent) developed inguinal nodal metastases during a mean follow-up period of 21.8 months (range, 13.5 to 58.3 months). The sensitivity of lymphatic mapping and sentinel lymph node biopsy in this series was 100 percent and the specificity was 97.3 percent. Therefore, we conclude that the use of lymphatic mapping and sentinel lymph node biopsy can accurately stage patients with melanoma of the lower extremity and provide a rational surgical approach for these patients.

Adolescent↗

Pathologic examination of the sentinel lymph node in melanoma.

The techniques of lymphatic mapping and sentinel lymph node biopsy are effective methods of accurately staging melanoma patients and identifying those who may benefit from further surgery or adjuvant chemotherapy. This article describes a standard pathology protocol for examination of sentinel lymph nodes in melanoma. Details of this standardized lymph node examination, institutional results using the protocol, and a literature review concerning lymph node findings in malignant melanoma are included.

Humans↗

Cost analysis of sentinel lymph node biopsy as an alternative to elective lymph node dissection in patients with malignant melanoma.

In the current era of managed care and cost containment, physicians and administrators are placed in the predicament of increasing quality of care while decreasing costs. The purpose of this article is to offer a cost analysis, while also demonstrating what patients, providers, payers, employers, and industry may stand to gain from establishing sentinel lymph node biopsy as a standard care in certain groups of patients.

Biopsy↗

Nitric oxide-dependent induction of glutathione synthesis through increased expression of gamma-glutamylcysteine synthetase.

The nitric oxide (NO) donors S-nitrosopenicillamine or DetaNONOate, which release NO at a rate of 0-15 nM sec-1, were exposed to rat aortic vascular smooth muscle cells for a period of 0-24 h. This treatment resulted in an increase in total glutathione levels of two- to threefold under conditions where no cytotoxicity was detected. The signaling pathways do not involve activation of protein kinase G Ialpha nor are they cGMP dependent. Oxidation of reduced glutathione (GSH) was found after exposure to NO for 3-4 h at rates of formation at or above 8 nM sec-1. Increased intracellular GSH was due to enhanced expression of the rate-limiting enzyme for GSH synthesis, gamma-glutamylcysteine synthetase. Since NO has been shown previously to protect cells against oxidative stress, we propose that the increase in GSH by NO is a potential mechanism for enhancing the antioxidant defenses of the cell. This result also has important implications for identifying redox-sensitive cell signaling pathways that can be activated by NO.

Animals↗

Translocation of PKC delta by insulin in a rat hepatoma cell line.

The aim of this study was to examine the effects of insulin and phorbol 12-myristate 13-acetate (PMA), an activator of classic and novel PKCs, on the translocation of PKC from cytosol to membrane in H4IIE (H4) rat hepatoma cells. Six PKC isoforms were expressed, including PKC-mu and PKC-lambda, identified for the first time in this hepatoma-cell line. Insulin induced translocation of PKC-delta from the cytosol to the membrane fraction as early as 15 min and maximally at 60 min with levels returning to that of controls by 180 min. Insulin also decreased levels of PKC-zeta in membranes at 5, 10, 15, and 30 min, but had no effect on cytosol levels. Ten minutes of PMA treatment translocated PKC-delta completely, and 24 h of PMA treatment downregulated PKC-delta. Neither acute nor chronic PMA had any effect on PKC-zeta. These studies establish the ability of both insulin and PMA to activate PKC-delta in H4 cells, and coupled with our previous work demonstrating a diminution of the effect of insulin on gene transcription in PKC downregulated cells, suggest that insulin may exert specific effects, in part, through a PKC-dependent pathway.

Animals↗

Insulin induction of pip 92, CL-6, and novel mRNAs in rat hepatoma cells.

Insulin directly affects many aspects of cellular metabolism. An additional, poorly studied effect of insulin is the regulation of multiple genes whose products are important in many cellular functions. Using differential screening techniques, we identified insulin-regulated genes induced in insulin-treated rat H4IIE (H4) hepatoma cells. Two of the mRNAs identified were homologous to the previously characterized mouse pip 92 and rat CL-6 immediate-early genes. The pip 92 clone was initially isolated from mitogen-stimulated mouse Balb/c 3T3 fibroblasts, whereas the CL-6 clone was first isolated from regenerating rat liver. In this article, we demonstrated that in rat H4 cells, the transcription rates of both pip 92 and CL-6 are induced by insulin alone. Additionally, we showed that the transcription rates of two other genes, whose sequences are not homologous to any other sequences in gene bank ("novel genes"), were rapidly and transiently induced by insulin. These results demonstrate that insulin regulates the expression of several novel genes with a time-course similar to members of the immediate-early response gene family.

3T3 Cells↗

Pioglitazone: in vitro effects on rat hepatoma cells and in vivo liver hypertrophy in KKAy mice.

Pioglitazone increases insulin sensitivity in vivo and in vitro. The effects of this agent on insulin-induced DNA synthesis and hepatic cell growth have not been determined. We examined the ability of pioglitazone to enhance basal and insulin-stimulated DNA synthesis in rat H4IIE (H4) hepatoma cells, and to alter liver weight and histology in diabetic KKAy mice. Treatment of H4 cells with increasing concentrations of pioglitazone for 30 h increased basal DNA synthesis 1.6- to 1.8-fold. With pioglitazone pretreatment and submaximal insulin concentrations, DNA synthesis was significantly increased from 2.1-fold (insulin 10(-12) mol/l alone) to 3.9-fold (insulin 10(-12) mol/l + pioglitazone 10(-6) mol/l). At maximal concentrations of insulin, the enhancement of DNA synthesis increased from 7.4-fold (insulin 10(-8) mol/l alone) to 16.2-fold (insulin 10(-8) mol/l + pioglitazone 10(-6) mol/l). Glyburide did not increase basal or insulin-stimulated DNA synthesis. In diabetic KKAy mice, serum glucose levels decreased and body weight, liver weight and liver weight as a percentage of body weight increased following pioglitazone treatment. Histological studies demonstrated marked hepatocyte distension. Our findings suggest that pioglitazone acts as an insulin sensitizer in rat hepatoma cells, increasing basal and insulin-stimulated DNA synthesis, and stimulating fat synthesis and liver hypertrophy in diabetic KKAy mice.

Animals↗

Pathologic examination of the sentinel lymph node.

One of the most important prognostic indicators in patients with malignant melanoma is lymph node status. While the five-year survival of stage I and II patients (without clinical adenopathy) is approximately 80 percent, this drops to 36-50 percent in patients with clinical or microscopic lymph node involvement. Other factors within lymph node specimens which affect disease-free and overall survival are the number of positive nodes (1 vs. 1-3 vs. 4 or greater) and the presence of extracapsular extension. Recently, the technique of sentinel lymphadenectomy has been developed to facilitate detection of metastatic disease in regional lymph nodes. Successful completion of this procedure requires a specialized but multidisciplinary approach, utilizing the surgeon, oncologist, nuclear radiologist, and pathologist. The pathologist's role is pivotal in this process, because identification of melanoma metastasis in the sentinel lymph node(s) is not only an important prognostic indicator but also dictates whether the patient will receive further surgery and adjuvant chemotherapy. Therefore, the goal of the pathologist in examining the sentinel lymph node is to maximize identification of nodal metastases of malignant melanoma. This is accomplished by following a standard protocol which fully utilizes all tissue submitted in concert with commonly available immunohistochemical techniques.

3,3'-Diaminobenzidine↗

The clinical relevance of sentinel lymph nodes identified with radiolymphoscintigraphy.

BACKGROUND: The purpose of this case report is to illustrate the utility of radio-guided mapping of sentinel lymph nodes (SLN's) as demonstrated by the technique's successful identification of nodes containing metastatic disease that would have been left behind if only the visual-oriented vital blue dye mapping technique had been used. METHOD: The patient underwent preoperative lymphoscintigraphy and intra-operative lymphatic mapping using vital blue dye and radiolymphoscintigraphy using the Neoprobe (handheld gamma probe). Nodes which were blue and/or "hot" (i.e., radioactive counts were three times the background count) were considered SLN's. RESULTS: Four SLN's were harvested, all of which were "hot" but only one of which was both "hot" and blue. Pathology revealed that the two SLN's positive for metastatic disease were not blue. CONCLUSION: While the blue dye lymphatic mapping technique provides the surgeon with a visual road map in the identification of SLN's, the Neoprobe increases the success rate of localization when compared to vital blue dye mapping due to the reliable migration of radiocolloid to the SLN's in the regional basin. Radiolymphoscintigraphy also increases the accuracy and efficiency of the SLN harvest by providing a directed dissection to the level of the nodes in the basin. The Neoprobe increases the yield of SLN's, some of which are clinically relevant since they contain metastatic disease.

Coloring Agents↗