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Biomedical subjects

R A Robinson

Publications and source records attributed to R A Robinson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Binding motifs of copolymer 1 to multiple sclerosis- and rheumatoid arthritis-associated HLA-DR molecules.

Copolymer 1 (Cop 1, poly (Y, E, A, K)) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS). Cop 1 binds promiscuously, with high affinity and in a peptide-specific manner to purified MS-associated HLA-DR2 (DRB1*1501) and rheumatoid arthritis-associated HLA-DR1 (DRB1*0101) or HLA-DR4 (DRB1*0401) molecules. In the present work at least 95% of added Cop 1 could be bound to recombinant "empty" HLA-DR1 and -DR4, and 80% could be bound to HLA-DR2 proteins. Amino acid composition, HPLC profiles, and sequencing patterns of Cop 1 eluted by acid extraction from HLA-DR molecules were similar to those of the unseparated Cop 1. Protruding N-terminal ends of Cop 1 bound to HLA-DR1, -DR2, or -DR4 molecules were then treated with aminopeptidase I, followed by elution, HPLC, and pool sequencing. In contrast to untreated or unbound Cop 1, this material exhibited distinct motifs at some positions with increases in levels of E at the first and second cycles, of K at the second and third cycles, and of Y (presumably at P1 of the bound peptide) at the third to fifth cycles, regardless of the HLA-DR molecule employed. No preference was seen at the following cycles that were mainly A. These first pooled HLA-DR binding epitopes provide clues to the components of Cop 1 that are biologically active in suppressing MS and possibly rheumatoid arthritis.

Amino Acid Sequence↗
PubMed1999

Malignant melanomas of the parotid: comparison of survival for patients with metastases from known vs unknown primary tumor sites.

BACKGROUND: Malignant melanoma (MM) rarely affects the parotid, and usually this diagnosis will herald a search for a primary skin neoplasm. Occasionally, no primary tumor is ever found, raising questions regarding prognosis and the issue of primary melanoma of the parotid. OBJECTIVE: To evaluate retrospectively the clinical and histological features of MM involving the parotid in 19 patients. DATA SOURCES: Pathology and hospital files at 3 tertiary care university hospitals. STUDY SELECTION: Patients with MM within the parotid with adequate histopathologic and immunohistochemical documentation, as well as clinical information regarding patient outcome. DATA EXTRACTION: In 6 patients, no extraparotid MM was ever identified. After parotidectomy, 5 patients (including 1 patient who died of other causes) were melanoma free at a mean of 4.2 years (range, 14 months to 7.5 years). Only 1 patient died of disease after 17 months. An extraparotid primary tumor was present in 13 patients, 10 with dermal and 3 with mucosal sites. At follow-up, only 1 of these patients was disease free after 2 years. Nine patients died of melanoma after a mean of 2.6 years (range, 10 months to 5 years); the other 3 had evidence of metastatic disease at a mean of 4.3 years (range, 3-6 years). Nondermal sites of primary tumors were the nasal cavity, sclera, and conjunctiva. DATA SYNTHESIS: Patients with metastatic MM from unknown primary tumors have a longer disease-free survival than those with metastases from known primary disease. CONCLUSIONS: Although rare, MM should be considered in the differential diagnosis of parotid tumors. Unusual mucosal or ocular sites should be considered in the search for possible primary tumor sites to avoid treatment delay. These data support the idea that patients with metastatic MM from unknown primary tumors may follow a more improved course than that of patients with metastases from known primary disease.

Adult↗
PubMed1999

National Cancer Data Base report on cancer of the head and neck: acinic cell carcinoma.

BACKGROUND: Management of acinic cell carcinoma is based on reports of small numbers of cases accrued over several decades. METHODS: The National Cancer Data Base (NCDB) identified 1353 cases of acinic cell carcinoma of the head and neck for the years 1985 to 1995. Chi square analyses of selected contingency tables and Wilcoxon regression analyses of selected survival stratifications are presented. RESULTS: Five-year survival was 83.3% (observed) and 91.4% (disease specific). Worse survival was associated with high grade (p < .0001), age greater or equal to 30 years (p = .0055), and the presence of metastatic disease (p < .0001). CONCLUSIONS: An aggressive subset of acinic cell carcinoma which is characterized by high grade and advanced stage rarely occurs in patients younger than 30 years old. Although better outcome was not statistically demonstrated for combined therapy, surgery with irradiation is the most common management in the United States for cases with regional metastases, high grade, and microscopic positive margins.

Carcinoma, Acinar Cell↗
PubMed1999

Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma.

The purpose of this study was to evaluate the clinical efficacy of ultrasmall superparamagnetic iron oxide particles as a magnetic resonance (MR) contrast agent in differentiating metastatic from benign lymph nodes. Eighteen patients with primary lung malignancy and suspected regional lymph node metastases underwent MR imaging before and after Combidex(R) infusion in a multi-institutional study. All MR sequences were interpreted by one or more board-certified radiologists experienced in imaging thoracic malignancy. Each patient was evaluated for the number and location of lymph nodes, homogeneity of nodal signal, and possible change of MR signal post contrast. All patients underwent resection or sampling of the MR-identified lymph node(s) 1-35 day(s) post contrast MR imaging. In all, 27 lymph nodes or nodal groups were available for histopathologic correlation. Combidex had a sensitivity of 92% and a specificity of 80% in identifying pathologically confirmed metastatic mediastinal lymph nodes. Based on our preliminary data, Combidex MR imaging may provide additional functional information useful in the staging of mediastinal lymph nodes.

Aged↗
PubMed1999

Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: a paraffin immunohistochemical study.

In this study, we assessed the frequency of cyclin D1 protein expression in normal and neoplastic parathyroid tissue (10 parathyroid carcinomas, 28 adenomas, 18 hyperplasias, and 32 normal parathyroid glands) with use of a monoclonal anticyclin D1 antibody and a heat-induced epitope retrieval method. Overexpression of cyclin D1 was identified in 10 (91%) of 11 biopsy specimens from 10 patients with parathyroid carcinomas and in 11 (39%) of 28 parathyroid adenomas. In addition, 11 (61%) of 18 cases of parathyroid hyperplasia also expressed cyclin D1 protein, an observation not reported previously. These results confirm the high frequency of cyclin D1 expression in parathyroid carcinomas and adenomas. In addition, the results of this study indicate that overexpression of cyclin D1 protein is not limited to neoplastic proliferations of parathyroid tissue but is also seen in non-neoplastic proliferations of parathyroid gland. Cyclin D1 protein expression was rarely (<6%) present in normal parathyroid tissue.

Adenoma↗
PubMed1999

H-ras and K-ras gene mutations in primary human soft tissue sarcoma: concomitant mutations of the ras genes.

ras gene mutations have been described with varying frequency in several types of human malignancies. To determine the incidence and type of ras mutations in human soft tissue tumors, we studied 45 sarcomas, including 27 malignant fibrous histiocytomas (MFHs), 10 liposarcomas, 2 rhabdomyosarcomas, and 6 leiomyosarcomas. Al of the tumors were investigated by direct sequence analysis with the automated DNA sequencing of polymerase chain reaction-amplified ras sequences. Twenty (44%) of the sarcomas examined harbored K-ras mutations, 18 (90%) of which were MFHs. All of the K-ras mutations were G-to-A transition mutations in the second position of codon 13 (glycine --> aspartic acid). Of the samples with K-ras activation, 7 (16% of the total of 45 tumors), including 6 MFHs and 1 leiomyosarcoma, also contained H-ras mutation. All of the tumors that showed H-ras alteration had G-to-T transversion mutations in the second base of codon 12 (glycine --> valine). These data possibly implicate that ras gene activation may be a relatively uncommon event in soft tissue tumors, with the exception of MFH. It is suggested that the oncogenic process underlying the development of tumors between these groups may be different and that ras gene mutations may play a role in the etiology and/or progression of MFH. It is noteworthy that when ras gene activation occurs in sarcoma, it predominantly affects the K-ras gene, particularly codon 13. Moreover, H-ras mutations in our samples were detected only in association with tumors that also displayed K-ras-mutated genes. This study demonstrates for the first time concomitant mutations in two different members of the ras gene family in sarcoma

Adolescent↗
PubMed1999

The variable presentation and natural history of Langerhans cell histiocytosis.

Langerhans cell histiocytosis is not a well defined or predictable disease. Instead, it is a spectrum of disorders of unknown etiology that vary widely in presentation and natural history, but have in common the proliferation of histiocytic cells and infiltration of these cells into normal tissues. Although the lesions of Langerhans cell histiocytosis consist primarily of histiocytes, eosinophils are a prominent feature in some lesions. Lesions may develop in any tissue, but bone, skin and lymph nodes are the most commonly affected, and more than 75% of patients have skeletal lesions. Bone lesions caused by Langerhans cell histiocytosis vary from focal sharply defined areas of bone lysis to diffuse osteopenia and can resemble lesions caused by a wide variety of metabolic, infectious and neoplastic diseases. The natural history varies from a benign disorder that resolves spontaneously to a progressive fatal disease. In general, the younger the individual at the time of onset of the disease, the poorer the prognosis and the more extensive the disease. Treatment may include surgery, chemotherapy and radiation therapy, depending on the extent and severity of the disease.

Disease Progression↗
PubMed1998

The National Cancer Data Base report on cancer of the head and neck.

BACKGROUND: The National Cancer Data Base (NCDB), a large sample of cancer cases accrued from hospital-based cancer registries, is sponsored by the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The NCDB permits a detailed analysis of case-mix, treatment, and outcome variables. OBJECTIVE: To provide an overview of the contemporary status of the subset of patients with head and neck cancer in the United States. METHODS: The NCDB, which obtains data from US as well as Canadian and Puerto Rican hospitals, accrued 4 583 455 cases of cancer between 1985 and 1994. Of these cases, 301350 (6.6%) originated in the head and neck. We address 295022 cases of head and neck cancer limited to the 50 United States and District of Columbia. Cases were segregated into an earlier group (1985-1989) to permit 5-year follow-up and into a later group (1990-1994) to analyze a more contemporary group. Comparison between both periods permits identification of trends. RESULTS: The largest proportion of cases arose in the larynx (20.9%) and oral cavity, including lip (17.6%) and thyroid gland (15.8%). Squamous cell carcinoma (55.8%) was the most common histological finding, followed by adenocarcinoma (19.4%) and lymphoma (15.1%). Income level (low), race (African American), and tumor grade (poorly differentiated) were most notably associated with advanced stage. Treatment was most commonly surgery alone (32.4%), combined surgery with irradiation (25.0%), and irradiation alone (18.9%). Overall 5-year, disease-specific survival was 64.0%. Cancer of the lip demonstrated the best survival (91.1%) and cancer of the hypopharynx the worst survival (31.4%). CONCLUSIONS: This NCDB analysis of cancer of the head and neck provides a contemporary overview of head and neck cancer in the United States. It also serves to introduce a series of NCDB articles that address specific anatomical sites and histological types through separate, detailed analysis.

Adult↗
PubMed1998

Risk factors for malignancy in adult tonsils.

BACKGROUND: Tonsillectomy in adults (age 18 years and older) is performed for a variety of conditions. The palatine tonsils may harbor carcinoma or lymphoma, and this potentially unanticipated finding may follow routine tonsillectomy in the adult. The ability to preoperatively identify adult tonsillectomy patients at increased risk for tonsillar malignancy could sensitize the clinician to this possibility and the potential need for expedited rather than routine tonsillectomy scheduling. METHODS: A retrospective review of 476 consecutive adult patients who underwent tonsillectomy during the last 10 years at the University of Iowa Hospitals and Clinics was undertaken. Proposed risk factors for tonsillar malignancy included a prior history of head and neck cancer, tonsillar asymmetry, palpable firmness or visible lesion in the tonsil, neck mass, unexplained weight loss, and unexplained constitutional symptoms. These risk factors were correlated with the pathologic diagnosis in the reviewed cases. RESULTS: Of these 476 patients, 25 had malignant tonsil pathology. No patient without risk factors was found to have malignancy on pathologic evaluation of the tonsils. Of the 25 patients with malignant tonsillar pathology, 23 had two or more risk factors, and 2 patients had one risk factor. Tonsillar asymmetry, found in 20 of the 25 cases, was the risk factor most frequently associated with malignant pathology. CONCLUSIONS: These results indicate that the presence of certain preoperatively identifiable risk factors are associated with the pathologic finding of malignancy in adult tonsillectomy specimens. Based on these criteria, a model which is predictive of the presence of tonsil malignancy may be constructed.

Adult↗
PubMed1998

Structural characterization of recombinant hepatitis E virus ORF2 proteins in baculovirus-infected insect cells.

The hepatitis E virus (HEV) capsid antigen has been proposed as a candidate subunit vaccine for the prevention of hepatitis E. The full-length HEV ORF2 protein product is predicted to contain 660 amino acids and to weigh 72,000 daltons. Expression of the HEV ORF2 capsid gene from recombinant baculoviruses in insect cells produced multiple immunoreactive proteins ranging in size from 30 to 100 kDa. The most abundant HEV proteins had molecular weights of 72, 63, 56, and 53 kDa. Temporal expression kinetics of these viral polypeptides indicated that the 72- and 63-kDa polypeptides were produced abundantly within the initial 36 h. postinfection but were replaced by 56- and 53-kDa polypeptides in the cell and medium, respectively, by 48 h postinfection. The 53-kDa protein was secreted as early as 24 h. postinfection, and accumulation in the medium peaked by 72 h postinfection. Purification of the 53-, 56-, and 63-kDa viral polypeptides was accomplished by anion-exchange and subsequent gel filtration chromatography. Sequence analysis of the 53-, 56-, and 63-kDa HEV polypeptides indicated that the amino terminus was amino acid residue 112 of the predicted full-length protein product. The results of carboxy terminal amino acid sequencing indicated that the carboxy terminus of the 53-, 56-, and 63-kDa HEV proteins was located at amino acid residues 578, 607, and 660, respectively. The molecular masses of the 53- and 56-kDa HEV polypeptides were 53,872 and 56,144 as determined by mass spectroscopy.

Amino Acid Sequence↗
PubMed1998

Granular cell tumour of the larynx.

Granular cell tumour (GCT) is a benign tumour with abundant eosinophilic cytoplasm filled with granules of varying sizes. These granules are the defining characteristic of the GCT and are believed to represent lysosomes in varying stages of fragmentation. The commonly used term granular cell myoblastoma, found in the older literature, is a misnomer because the tumour is clearly not of muscle origin. Among the major theories of origin, some support the tumour's derivation from neuronal tissue, histiocytes, fibroblast or Schwann cells. In the larynx, pseudoepitheliomatous hyperplasia may predispose to confuse the GCT with squamous cell carcinoma. The most common region of GCT is in the head and neck, accounting for approximately 30 to 50 per cent of all lesions. The larynx is relatively an uncommon location for these tumours, accounting for approximately three to 10 per cent of the reported cases. Affected patients typically present with persistent hoarseness, stridor, haemoptysis, dysphagia, and otalgia, but the tumour may be asymptomatic and be discovered only incidentally during a routine examination. Complete excision with an attempt to maintain normal structures generally results in cure. We present the case of a patient with typical features of a GCT of the larynx. The gross appearance, histopathology and brief discussion of the current literature are also presented.

Adult↗
PubMed1998

Comparison of concentric needle versus hooked-wire electrodes in the canine larynx.

BACKGROUND: The use of a specific electrode type in laryngeal electromyography has not been standardized. Laryngeal electromyography is usually performed with hooked-wire electrodes or concentric needle electrodes. Hooked-wire electrodes have the advantage of allowing laryngeal movement with ease and comfort, whereas the concentric needle electrodes have benefits from a technical aspect and may be advanced, withdrawn, or redirected during attempts to appropriately place the electrode. OBJECTIVES: This study examines whether hooked-wire electrodes permit more stable recordings than standard concentric needle electrodes at rest and after large-scale movements of the larynx and surrounding structures. A histologic comparison of tissue injury resulting from placement and removal of the two electrode types is also made by evaluation of the vocal folds. METHODS: Electrodes were percutaneously placed into the thyroarytenoid muscles of 10 adult canines. Amplitude of electromyographic activity was measured and compared during vagal stimulation before and after large-scale laryngeal movements. Signal consistency over time was examined. Animals were killed and vocal fold injury was graded and compared histologically. RESULTS: Waveform morphology did not consistently differ between electrode types. The variability of electromyographic amplitude was greater for the hooked-wire electrode (p < 0.05), whereas the mean amplitude measures before and after large-scale laryngeal movements did not differ (p > 0.05). Inflammatory responses and hematoma formation were also similar. CONCLUSIONS: Waveform morphology of electromyographic signals registered from both electrode types show similar complex action potentials. There is no difference between the hooked-wire electrode and the concentric needle electrode in terms of electrode stability or vocal fold injury in the thyroarytenoid muscle after large-scale laryngeal movements.

Action Potentials↗
PubMed1998

The utility of histological examination of tissue removed during elective joint replacement. A preliminary assessment.

The utility of histological examination of tissue removed during elective joint replacement has not been determined. During a one-year period, tissue removed during 168 total joint replacements was submitted for histological examination. The clinical and histological diagnoses, the cost of the histological study, and the clinical course were determined for all joints. Degenerative joint disease, rheumatoid arthritis, and avascular necrosis accounted for 98 per cent of the histological diagnoses. There were sixteen discrepancies between the clinical and histological diagnoses. The histological diagnosis did not affect the treatment of fifteen of these joints. However, the treatment was altered for one joint that had a clinical diagnosis of degenerative joint disease and a histological diagnosis of osteomyelitis; on review, the initial histological diagnosis was determined to be incorrect. In 1996 dollars, the cost of histological examination for all 168 joints was $10,698.24. Although there would be considerable cost-savings on a population basis if histological examination were not performed, this savings must be weighed against the effect of a misdiagnosis on the management of a particular patient.

Adult↗
PubMed1997

Biochemical and functional characterization of soluble multivalent MHC L(d)/Fc gamma 1 and L(d)/Fc mu chimeric proteins loaded with specific peptides.

Central to the specificity of the immune system is the interaction between the T cell receptor and the major histocompatibility complex (MHC)-peptide ligand complex. To better understand the nature of this interaction, and to investigate possible avenues for specific therapeutic intervention, we have produced soluble recombinant molecules that can modulate antigen-specific T cells. Our approach involved the construction of recombinant murine genes composed of the MHC class I gene H-2L(d) and the Fc portion of immunoglobulin (Ig) heavy chain genes mu or gamma1. Stable transfectants of these L(d)/Fc gamma1 and L(d)/Fc mu genes generated correctly spliced transcripts and were capable of secreting chimeric protein. Immunoprecipitation analyses demonstrated the presence of chimeric L(d)/ Fc gamma1 and L(d)/Fc mu monomers of approximately 69 kDa and 90 kDa, respectively, as well as chimeric dimers under nonreducing conditions. The capacity of L(d)/Ig molecules to bind specific peptide ligands was demonstrated using radiolabeled peptides or with monoclonal reagents that specifically identify peptide-induced conformational changes in the L(d) ligand binding site. Soluble divalent L(d)/Fc gamma1 molecules were loaded with the murine cytomegalovirus-derived peptide and other L(d)-specific peptide ligands and subsequently isolated and purified. Peptide-loaded L(d)/Fc gamma1 molecules were capable of inhibiting the response of class I-restricted T cells in vitro in a peptide-specific fashion. The development of soluble multivalent chimeric proteins that possess unique properties of both the MHC class I and Ig molecules provides a valuable reagent for the study of potential mechanisms of in vitro and in vivo immune modulation.

Animals↗