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Biomedical subjects

R L Sanchez

Publications and source records attributed to R L Sanchez.

At least 19 recordsLinked to original sources

Mucoepidermoid carcinoma with cutaneous presentation.

Mucoepidermoid carcinomas are malignant neoplasms that rarely involve the skin. Composed of both mucus-secreting cells and epidermoid-type cells in various proportions, mucoepidermoid carcinomas occur most commonly in salivary glands. In this case report, we describe a high-grade mucoepidermoid carcinoma with cutaneous involvement. Although this patient was referred for Mohs' micrographic surgery, further evaluation showed either direct or metastatic extension from the parotid gland to skin and distant metastases to the lung and bone. Despite extensive bone involvement, serum levels of ionized calcium, phosphorus, and lactate dehydrogenase remained normal. In view of the widespread metastases, the treatment plan was altered to radiotherapy and chemotherapy instead of surgery. Instructive lessons from this case include the recognition by dermatologists of this rare entity, the importance of a detailed history and complete evaluation of the patient before determining appropriate therapy, and the necessity of individualizing diagnostic tests to a particular patient.

Biopsy, Needle

Elastoderma.

Elastoderma is an exceedingly rare condition that is characterized clinically as an acquired localized laxity of skin resembling cutis laxa and histologically as an excessive accumulation of pleomorphic elastic structures within the dermis. We report the case of a 27-year-old white man with a 2-year history of lax, extensible, wrinkled skin with areas of protrusion and ulceration localized to the anterior aspect and back of the neck. Histologic examination of specimens from the affected area revealed increased masses of intertwined thin, elastic fibers without calcification in the papillary and upper reticular dermis. Transmission and scanning electron microscopy demonstrated irregular deposition of elastic material at the periphery of elastic tissue fibers, with grapelike globular structures. To our knowledge, this is the second reported case of elastoderma.

Adult

The Q-switched Alexandrite laser's effects on tattoos in guinea pigs and harvested human skin.

BACKGROUND: Developmental work in tattoo removal is currently carried out in animal models whose skin has different optical and mechanical properties from human skin. OBJECTIVE: To observe laser effects on tattoos in a new human skin model and that of in vivo guinea pig skin. METHODS: A comparison of the efficacy of the Q-switched Alexandrite laser (750 nm, 100-120 nanoseconds) in tattooed harvested human skin and guinea pig skin was performed. Visual assessments as well as histologic and electron microscopy evaluation before and after treatment are reported. RESULTS: Mild to moderate clearing of black tattoo pigment, as judged by visual assessment, was found after one laser treatment in both the in vitro human skin model and guinea pig skin. Blue and green ink showed similar results to black ink in human skin whereas red and yellow ink did not respond in our model. CONCLUSION: Possible mechanisms of tattoo lightening and the usefulness of the in vitro human skin model are discussed.

Animals

Emergency department response to battered women in Massachusetts.

STUDY OBJECTIVES: To determine the prevalence of written protocols for response to battered women and the perceived incidence of such cases in the emergency department and to examine general issues of responsiveness to this patient population. DESIGN: Questionnaires were sent to all 90 EDs in Massachusetts in 1991, and a response rate of 79% was obtained. TYPE OF PARTICIPANTS: ED directors (75% of respondents). MEASUREMENTS: Self-reported response to written survey. MAIN RESULTS: Fourteen EDs (20%) reported having a written protocol in use. 58% of the EDs estimated that they see five or fewer battered women each month. Half of respondents estimated that 2% or less of adult female trauma stems from battering. Few differences were found between EDs with and without protocols. CONCLUSION: In 1991, prior to several initiatives on domestic violence in the health care sector, written protocols for response to battered women were rare. The majority of EDs perceived battering as an infrequent cause of adult female trauma, contrary to prior research findings.

Clinical Protocols

Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene.

OBJECTIVE: This study determined whether genomic amplification of HER-2/neu or mutations of the p53 and ras genes were present in gastrinomas. SUMMARY BACKGROUND DATA: Amplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto-oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome. METHODS: The differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present. RESULTS: Amplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4- to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1- to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes. CONCLUSIONS: Amplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.

Base Sequence

Diffuse dermal angiomatosis: a variant of reactive cutaneous angioendotheliomatosis.

Reactive angioendotheliomatosis (RA) is a rare, benign disease. Affected patients present with self-limited, erythematous to violaceous plaques. The clinical lesions are due to intravascular hyperplasia of cytologically banal endothelial cells in the dermis. We report 2 patients who presented with ulcerated, violaceous plaques on the lower extremities. Both had severe peripheral vascular atherosclerotic disease requiring bypass grafts. Unlike previously described cases of RA, our patient's lesions were due to a diffuse proliferation of endothelial cells in the reticular dermis with only minimal, focal intravascular proliferation of these cells. Positive immunostaining with antibodies to Factor VIII-related and CD34 antigens adds evidence that the proliferated cells in the dermis were endothelial cells.

Angiomatosis

Cutaneous manifestations of histoplasmosis in the acquired immune deficiency syndrome.

The clinical and histologic features of cutaneous histoplasmosis in three patients with acquired immunodeficiency syndrome (AIDS) are described. The patients presented with multiple discrete papules on the extremities, trunk, and face, some of which were follicular. Histologically, the skin biopsies were characterized by a sparse perivascular infiltrate with polymorphonuclear leukocytes, lymphocytes, and occasional histiocytes. Prominent leukocytoclasia and associated dermal necrosis were seen around the superficial blood vessels of the dermis. The Histoplasma capsulatum organisms were for the most part extracellular and difficult to visualize on the hematoxylin and eosin-stained sections. A diagnosis of atypical leukocytoclastic vasculitis was considered. Histoplasmosis is a relatively common mycosis among AIDS patients, and it is sometimes the first manifestation of the syndrome. The clinical and histologic findings described herein may be relatively common among AIDS patients and are quite different from those of classic disseminated histoplasmosis.

AIDS-Related Opportunistic Infections

Proteolysis of an active site peptide of lactate dehydrogenase by human immunodeficiency virus type 1 protease.

The muscle and heart lactate dehydrogenase (LDHs) of rabbit and pig are specifically cleaved at a single position by HIV-1 protease, resulting in the conversion of 36-kDa subunits of the oligomeric enzymes into 21- and 15-kDa protein bands as analyzed by SDS-PAGE. While the proteolysis was observed at neutral pH, it became more pronounced at pH 6.0 and 5.0. The time courses of the cleavage of the 36-kDa subunits were commensurate with the time-dependent loss of both quaternary structure and enzymatic activity. These results demonstrated that deoligomerization of rabbit muscle LDH at acidic pH rendered its subunits more susceptible to proteolysis, suggesting that a partially denatured form of the enzyme was the actual substrate. Proteolytic cleavage of the rabbit muscle enzyme occurred at a decapeptide sequence, His-Gly-Trp-Ile-Leu*Gly-Glu-His-Gly-Asp (scissile bond denoted throughout by an asterisk), which constitutes a "strand-loop" element in the muscle and heart LDH structures and contains the active site histidyl residue His-193. The kinetic parameters Km, Vmax/KmEt, and Vmax/Et for rabbit muscle LDH and the synthetic decapeptide Ac-His-Gly-Trp-Ile-Leu*Gly-Glu-His-Gly-Asp-NH2 were nearly identical, suggesting that the decapeptide within the protein substrate is conformationally mobile, as would be expected for the peptide substrate in solution. Insertion of part of this decapeptide sequence into bacterial galactokinase likewise rendered this protein susceptible to proteolysis by HIV-1 protease, and site-directed mutagenesis of this peptide in galactokinase revealed that the Glu residue at the P2' was important to binding to HIV-1 protease. Crystallographic analysis of HIV-1 protease complexed with a tight-binding peptide analogue inhibitor derived from this decapeptide sequence revealed that the "strand-loop" structure of the protein substrate must adopt a beta-sheet structure upon binding to the protease. The Glu residue in the P2' position of the inhibitor likely forms hydrogen-bonding interactions with both the alpha-amide and gamma-carboxylic groups of Asp-30 in the substrate binding site.

Amino Acid Sequence

Percutaneous intraluminal US in the gallbladder and bile ducts.

The authors describe their initial experience with a dedicated intraluminal ultrasound (US) device that was coupled to a catheter and introduced percutaneously into the gallbladder and/or bile ducts. Access was created with interventional radiologic techniques in 22 patients and at laparoscopy in four patients. Thirty-one examinations in 26 patients revealed information on normal anatomy, pathologic processes, and responses to therapy. The pathologic processes seen included bile duct and gallbladder debris, stones, ductal strictures, and tumors. Additional information provided with this technique over other diagnostic studies included differentiation of intraluminal filling defects, examination of areas inaccessible to conventional imaging, and observations about the walls of the ducts and gallbladder. Percutaneous US examination of metallic stents within the bile ducts and of filling defects in the ducts at laparoscopic cholecystectomy was of particular interest and altered subsequent therapy. The procedure is simple, straightforward, and devoid of complications. While refinements and improvements are needed, this diagnostic technique holds promise.

Adult

Vasculitis in children.

Reviewed herein are the major types of vasculitis affecting children, including Henoch-Schönlein purpura, necrotizing vasculitis of small vessels, Kawasaki's disease, and, less commonly, classic polyarteritis nodosa, Wegener's granulomatosis, Churg Strauss syndrome, and lymphomatoid granulomatosis. The clinical features, diagnosis, treatment, and suspected etiologies and pathogenic mechanisms for each entity are discussed.

Child

Amplification of the HER-2/neu protooncogene in human endocrine tumors.

BACKGROUND: Amplification of HER-2/neu, a protooncogene related to the epidermal growth factor receptor, has prognostic significance in patients with breast cancer. Alterations in protooncogenes have not been determined for endocrine tumors in which prognosis is difficult to predict. We have addressed the question of whether amplification of HER-2/neu or epidermal growth factor receptor occurs in DNA from human endocrine tumor lines and have sought to characterize the HER-2/neu gene and its products in carcinoid tumors of the gut. METHODS: The differential polymerase chain reaction procedure was used to detect genomic amplification in DNA samples from human endocrine tumor cell lines (BON, SIM, STAN) and from paraffin-embedded samples of carcinoid tumors. Sequencing techniques were used to determine whether mutations of the transmembrane domain of HER-2/neu existed. We then further characterized the gene products (RNA and protein) in carcinoid tumors. RESULTS: Amplification of HER-2/neu was identified in all three endocrine tumor cell lines. HER-2/neu amplification was found in four of 10 carcinoid tumors of the gut; three of these four tumors were invasive or metastatic. In addition, HER-2/neu mRNA and protein were expressed in carcinoid tumors. CONCLUSIONS: Amplification of the HER-2/neu protooncogene occurs in endocrine tumors of the gut; quantitation of the actual copy number may be an important prognostic determinant. The unique human endocrine cell lines, established in our laboratory, will be useful models to further examine the significance of alterations of the HER-2/neu gene in endocrine tumors.

Carcinoid Tumor