Biomedical subjects

D J Lee

Publications and source records attributed to D J Lee.

At least 127 records · Page 7Linked to original sources

PubMed1998

Induction of an antigen-specific, CD1-restricted cytotoxic T lymphocyte response In vivo.

The majority of T cell responses are restricted to peptide antigens bound by polymorphic major histocompatibility complex (MHC) molecules. However, peptide antigens can be presented to T cells by murine non-MHC-encoded CD1d (mCD1) molecules, and human T cell lines specific for nonpeptide antigens presented on CD1 isoforms have been identified. It is shown here that antigen-specific, mCD1-restricted lymphocytes can be generated in vivo by immunizing mice with a combination of plasmids encoding chicken ovalbumin, murine CD1d, and costimulatory molecules. Splenocytes from immunized mice have CD1d-restricted, MHC- unrestricted, ovalbumin-specific cytolytic activity that can be inhibited by anti-CD1 antibodies as well as a competing CD1-binding peptide. These results suggest a physiologic role for murine CD1d to present exogenous protein antigens.

Amino Acid Sequence↗

PubMed1998

Squamous cell granulomas of the neck: histologic regression of metastatic squamous cell carcinoma following chemotherapy and/or radiotherapy.

BACKGROUND: For patients with squamous cell carcinoma of the head and neck (HNSCC), persistence of cervical adenopathy following organ-preservation therapy is a strong predictor of locoregional failure. Squamous cell granulomas of the neck may represent a regressed state of metastatic HNSCC; however, relevant clinicopathologic features of this lesion including its morphologic characteristics, association with therapy, and relationship to disease progression are not well defined. METHODS: We reviewed 866 consecutive neck dissections performed at The Johns Hopkins Hospital from 1984 to 1996. A total of eight cases showing a foreign-body giant-cell reaction to keratin in the absence of viable tumor formed the basis of this study. RESULTS: All eight cases were from patients with stage III or IV HNSCC with concurrent neck masses. Patients were initially treated by chemotherapy (n = 1), radiotherapy (n = 1), or chemotherapy plus radiotherapy (n = 6); and all patients subsequently underwent neck dissection for persistence of their neck masses. Histologically, the neck lesions were characterized by a foreign-body giant-cell reaction to keratin and extensive scarring. None (0%) of the patients developed recurrent regional disease in the treated neck. Two (25%) of the patients had tumor recurrence at the primary site. Two (25%) of the patients developed widely metastatic disease. CONCLUSIONS: These observations suggest that squamous cell granulomas represent histologic regression of metastatic squamous cell carcinoma in patients with HNSCC treated by chemotherapy and/or radiotherapy. Although persistent cervical adenopathy is an established risk factor for locoregional failure in this group of patients, squamous cell granulomas of the neck paradoxically may reflect enhanced regional tumor sensitivity to cytotoxic agents.

Adult↗

PubMed1998

CT-simulator based brachytherapy planner: seed localization and incorporation of biological considerations.

Radiation dose prescription, interpretation, and planning can be problematic for brachytherapy due to high spatial heterogeneity, varying and various dose rates, absence of superimposed calculated isodose distributions onto affected tissues, and lack of dose volume histograms. A new treatment planner has been developed to reduce these limitations in brachytherapy planning. The PC-based planning system uses a CT-simulator to sequentially scan the patient to generate orthogonal images (to localize seed positions) and subsequently axially scan the patient. This sequential scanning procedure avoids using multiple independent patient scans, templates, external frames, or fiducial markers to register the reconstructed seed positions with patient contours. Dose is computed after assigning activity to (low dose rate) Ir192, linear Cs137, or I125 seeds or dwell times (high dose rate) to the Ir192 source. The planar isodose distribution is superimposed onto axial, coronal, or sagittal views of the tissues following image reconstruction. The treatment plan computes (1) direct and cumulative volume dose histograms for individual tissues, (2) the average, standard deviation, and coefficient of skewness of the dose distribution within individual tissues, (3) an average (over all tissue pixels) survival probability (S) and average survival dose DASD for a given radiation treatment, (4) normal tissue complication probability (NTCP) delivered to a given tissue. All four computed quantities account for dose heterogeneity. These estimates of the biological response to radiation from laboratory-based studies may help guide the evaluation of the prescribed low- or high-dose rate therapy in retrospective and prospective clinical studies at a number of treatment sites.

Brachytherapy↗

PubMed1998

Effect of interstitial and/or systemic delivery of tirapazamine on the radiosensitivity of human glioblastoma multiforme in nude mice.

The purpose of this study was to investigate the feasibility and the efficacy of administering tirapazamine by a slow-releasing polymer disc that was implanted interstitially into a U251 (human glioblastoma multiforme) tumor grown in nude mice. Tumor-bearing animals, with a tumor nodule 0.8 cm3 in size, were distributed to groups receiving combinations of empty or drug-containing polymer implants in the tumor or contralateral leg, intraperitoneal (i.p.) drug, and/or irradiation. The drug (i.p.) alone (14 mg/kg x6) or in combination with tumor drug implant (2 mg) did not significantly increase the tumor volume doubling time compared to that of control animals. Given with 12 Gy of irradiation in twice a day 2-Gy fractions, combined i.p. drug and tumor drug implant significantly delayed tumor growth compared to irradiation alone, which was not achieved with either drug treatment alone added to irradiation. Toxicity, as manifested by transient weight loss, was primarily seen in animals receiving radiation and i.p. tirapazamine. These results indicated that a slow-releasing tirapazamine disc can be produced and the addition of an interstitially implanted tirapazamine disc further increased the effectiveness of i.p. tirapazamine.

Animals↗

PubMed1998

Hypoxic cell cytotoxin tirapazamine induces acute changes in tumor energy metabolism and pH: a 31P magnetic resonance spectroscopy study.

Tirapazamine is a hypoxic cell cytotoxin in phase II/III trials. To further understand its mechanism of action in vivo, we examined the effect of tirapazamine on tumor energy metabolism and pH. RIF-1 and SCCVII tumors were grown subcutaneously in the flanks of C3H mice. Tumor energy metabolism, expressed as the ratio of inorganic phosphate to nucleotide triphosphate (Pi/NTP), and intracellular pH (pHi), were measured by 31P magnetic resonance spectroscopy (MRS). In RIF-1 and SCCVII tumors, tirapazamine increased the Pi/NTP ratio by 2.6-fold and 3-fold, respectively, within the first hour after an intraperitoneal dose of 0.3 mmol/kg. A corresponding decrease in pHi from 7.05+/-0.07 to 6.48+/-0.06, and 7.21+/-0.09 to 6.45+/-0.02 in RIF-1 and SCCVII tumors, respectively, was observed. The decrease in tumor 31P bioenergetics and pH was reversible, as exemplified by RIF-1 tumors, which showed a further increase in Pi/NTP ratio of 3.5-fold by 5-8 hr, returning to normal range at 24 hr. Corresponding pHi of RIF-1 tumors was 6.88+/-0.05 at 5-8 hr and 7.16+/-0.05 at 24 hr. We concluded that tirapazamine induces acute changes in tumor energy metabolism and pHi. These findings are relevant to the rational selection and optimal timing of coadministered therapy.

Animals↗

PubMed1998

Prevalence of uncorrected binocular distance visual acuity in Hispanic and non-Hispanic adults. Results from the HHANES and the NHANES I.

OBJECTIVE: This study aimed to provide a comparative analysis of American population-based prevalence of uncorrected binocular distance visual acuity in Hispanics and non-Hispanics. DESIGN: The study design was a population-based survey. PARTICIPANTS: Data from the Hispanic Health and Nutrition Examination Survey between 1982 and 1984 and the National Health and Nutrition Examination Survey I from 1974 through 1975 were analyzed to investigate the epidemiology of uncorrected binocular distance visual acuity in adults 25 to 74 years of age in Cuban Americans (N = 391), Mexican Americans (N = 1350), Puerto Ricans (N = 504), African Americans (N = 245), and non-Hispanic white Americans (N = 2571). MAIN OUTCOME MEASURE: Uncorrected binocular distance visual acuity in both eyes was assessed using Sloan letters or Landolt rings. RESULTS: Prevalence rates of 20/50 or worse uncorrected binocular distance visual acuity were 22%, 24%, 19%, 18%, and 32% for African Americans, Cuban Americans, Mexican Americans, Puerto Ricans, and non-Hispanic whites, respectively. After adjustment for gender and age, the rates were significantly higher (P < 0.05) for non-Hispanic whites compared to each of the other ethnic groups. Significant increases in the prevalence of 20/50 or worse distance visual acuity were observed for increasing age groups (25-39, 40-59, and 60-74 years) within each gender-ethnic subgroup. Analysis of differences in prevalence by gender (controlling for age) indicated a slightly higher prevalence of 20/50 or worse distance visual acuity in women than in men (range of odds ratios, 1.1-2.1). Based on 1993 census population estimates in the United States, more than 42 million adults 25 to 74 years of age have an uncorrected binocular distance visual acuity of 20/50 or worse. Approximately 1.7 million of these adults are of Hispanic origin. CONCLUSION: The prevalence of impaired uncorrected binocular distance visual acuity generally is lower in Hispanics than in non-Hispanic whites.

Adult↗

PubMed1998

Determination of carotid plaque risk by ultrasonic tissue characterization.

This in vitro study investigated the ability of ultrasonic tissue characterization (UTC) to discriminate between plaques from asymptomatic and symptomatic patients and to compare UTC findings with quantitative measurements of plaque morphology. A total of 34 plaque specimens removed at carotid endarterectomy were scanned transversely at intervals of 1 mm, and compared to tissue cross-sections examined by optical microscopy employing computer-assisted planimetry. UTC was performed by spectral analysis of backscattered radiofrequency signals. The slope, intercept and total power parameters of the spectrum were evaluated. Discriminant analysis was used to compare the ability of the UTC spectral parameters and morphological constituents to correctly classify plaques according to their symptom group membership. UTC correctly classified 88.2% of the plaques. Thrombus was present in 93.9% of the plaques, and there was little difference in the morphological constituents of plaques from asymptomatic and symptomatic patients. Morphological constituents correctly classified 60.7% of the plaques. We conclude, in this preliminary study, that UTC can discriminate between carotid plaques from asymptomatic and symptomatic patients with moderate accuracy, despite a similarity in their morphological composition. UTC discrimination is not related to differences in the type or amount of morphological constituents in the plaques.

Carotid Arteries↗

PubMed1998

Solitary plasmacytoma of the epiglottis: a case report and review of the literature.

A 59-year-old white male presented with a two-month history of dry cough and shortness of breath. At bronchoscopy, a 1 cm mass on the laryngeal surface of the epiglottis was found. Immunohistochemical stain of the biopsy specimen revealed a monoclonal proliferation of plasma cells. Serological tests revealed normal serum immunoglobulin levels, and a bone marrow aspirate and biopsy was also normal; no abnormalities were found on serum or urine electrophoresis. He received radiotherapy (50 Gy), and was doing well three years following therapy without evidence of disease.

Epiglottis↗

PubMed1998

Diabetes and hearing impairment in Mexican American adults: a population-based study.

Reports on the relationship between diabetes and hearing loss have been controversial. The present study examined this relationship in 1,740 Mexican American adults using data from the Hispanic Health and Nutrition Examination Survey. Hearing threshold levels were obtained for each participant at the following frequencies: 500, 1000, 2000, and 4000 Hertz (Hz). The thresholds from the worse hearing ear were used in the analyses. Diabetes and insulin use were assessed by self-report. The mean crude hearing thresholds in diabetics were significantly higher than in non-diabetics at each of the four frequencies. However, after adjustment for age, gender, and socioeconomic status, diabetics had a significantly higher mean threshold than non-diabetics only at 500 Hz (mean difference +/- SE: 2.8 +/- 1.2, p = 0.04). Diabetics who were not using insulin had significantly higher thresholds than those who were using insulin at 2000 (mean difference +/- SE: 5.6 +/- 2.6, p = 0.03) and 4000 Hz (7.7 +/- 3.3, p = 0.02). Also, at 4000 Hz, insulin users had a significantly lower mean threshold than non-diabetics (mean difference +/- SE: -4.9 +/- 1.6, p = 0.02). Our data suggest that associations between diabetes and decreased hearing acuity in the higher frequencies are present only amongst diabetic Mexican-Americans who do not use insulin.

Adult↗

PubMed1998

Evaluation of an improved scoring system for the grading of direct laryngoscopy.

A modified version of the Cormack and Lehane scoring system was prospectively evaluated in 663 patients requiring tracheal intubation. In the modified system, grade 2 (only part of the glottis visible) was divided into 2a (part of the cords visible) and 2b (only the arytenoids or the very posterior origin of the cords visible). One hundred and sixty-two intubations (24.4%) were scored as grade 2a and 43 (6.5%) as grade 2b, of which seven (4.3%) and 29 (67.4%), respectively, were difficult, defined as requiring more than one laryngoscopy or the use of specialist equipment. Grade 2b denotes a laryngoscopic view that is relatively common and is often associated with difficulty passing a tracheal tube. The modified scoring system thus provides more information than the original Cormack and Lehane system and its use should be considered when recording the ease of tracheal intubation in the anaesthetic record or in studies of tracheal intubation.

Adolescent↗

PubMed1998

Prevalence of unilateral hearing loss in children: the National Health and Nutrition Examination Survey II and the Hispanic Health and Nutrition Examination Survey.

We compared population-based prevalence rates of unilateral hearing loss among African-American, Cuban-American, Mexican-American, Puerto Rican, and non-Hispanic White children 6 to 19 yr of age. The prevalence (per thousand) of overall hearing loss (average decibel HTL >30) ranged from 6.4 in Mexican-Americans to 12.3 in Cuban-Americans. The prevalence of moderate to profound unilateral hearing loss (average decibel HTL >50) ranged from 0.0 in Cuban-Americans to 5.2 in Puerto Ricans. No statistically significant age or gender differences were found within any of the ethnic groups. Among these five ethnic groups, it is estimated that approximately 391,000 school-aged children in the United States have unilateral hearing loss.

Adolescent↗

PubMed1998

Occult tonsillar carcinoma in the unknown primary.

OBJECTIVES: Evaluate effectiveness of routine tonsillectomy in the assessment of patients with squamous cell carcinoma of the neck of unknown primary, and evaluate outcomes of this group compared with patients without a primary identified initially. STUDY DESIGN: A retrospective review of the medical records of 37 patients presenting with an unknown primary tumor over a 10-year period. METHODS: Charts were reviewed for age and sex of patients, methods of evaluation and diagnosis, sites of tissues obtained on biopsy, N stage of disease, and presence of extracapsular spread. Recurrence and survival data were collected over a mean follow-up period of 34 months. RESULTS: All primary lesions discovered through pathologic evaluation arose from the tonsil (9/9), and all were detected in patients undergoing tonsillectomy in conjunction with direct laryngoscopy. None of the patients (0/9) with occult tonsillar carcinoma have had recurrence, in contrast to 60% (15/25) of remaining patients. Patients with tonsillar primary lesions demonstrated less extracapsular spread of disease (25%) than patients without tonsillar primaries (67%), despite similar N staging within the two groups. CONCLUSIONS: Occult tonsillar carcinoma accounts for the unknown primary more frequently than was previously recognized. Bilateral tonsillectomy is recommended to increase the detection yield and to capture the rare case of bilateral disease. A lower incidence of extracapsular spread and reduced recurrence rates in patients with unknown primary tumors presenting as occult tonsillar carcinoma may contribute to the improved prognosis observed in this group.

Adult↗

PubMed1998

Race-specific cancer mortality in US firefighters: 1984-1993.

A mortality odds ratio (MOR) study of race-specific cancer risk among firefighters was conducted using 1984-1993 death certificate data from 24 states. The Bureau of the Census Index of Industries and Occupations was used to code occupation on death certificates. The overall cancer mortality was slightly elevated among white firefighters (MOR = 1.1; 95% confidence interval [CI] = 1.1-1.2), but the increase in overall cancer mortality among black firefighters was not significant (MOR = 1.2; 95% CI = 0.9-1.5). Only prostate cancer risk was elevated in both groups (whites: MOR = 1.2; 95% CI = 1.0-1.3; blacks: MOR = 1.9; 95% CI = 1.2-3.2). Among white firefighters, elevated site-specific cancer mortality risks were found for the following cancer sites: lip (MOR = 5.9; 95% CI = 1.9-18.3), pancreas (MOR = 1.2; 95% CI = 1.0-1.5), soft tissue sarcoma (MOR = 1.6; 95% CI = 1.0-2.7), melanoma (MOR = 1.4; 95% CI = 1.0-1.9), kidney and renal pelvis (MOR = 1.3; 95% CI = 1.0-1.7), non-Hodgkin's lymphoma (MOR = 1.4; 95% CI = 1.1-1.7), and Hodgkin's disease (MOR = 2.4; 95% CI = 1.4-4.1). We also observed a slightly elevated risk for bronchus and lung cancer (MOR = 1.1; 95% CI = 1.0-1.2). Among black firefighters, excess risks were found for cancers of the brain and central nervous system (MOR = 6.9; 95% CI = 3.0-16.0), colon (MOR = 2.1; 95% CI = 1.1-4.0), and nasopharynx (MOR = 7.6; 95% CI = 1.3-46.4). Future studies are needed to confirm the existence of differential cancer mortality risks among firefighters of different race/ethnic subpopulations.

Black or African American↗

PubMed1998

Increased c-fos mRNA expression by human fibroblasts contracting stressed collagen matrices.

We studied early changes in gene expression during fibroblast contraction of stressed collagen matrices. The level of c-fos mRNA increased dramatically and peaked 50 to 60 min after matrix contraction was initiated. This response did not require serum and could not be accounted for simply by disruption of the actin cytoskeleton. Increased c-fos mRNA levels required Ca2+ influx but not the cyclic AMP or extracellular signal-regulated kinase (ERK 1/2) signaling pathways, both of which are activated when fibroblasts contract stressed collagen matrices. The levels of two other immediate-early genes, fosb and c-jun, also increased transiently after fibroblast contraction, whereas the levels of fra-1, fra-2, c-myc, and the transcription factor NF-kappaB remained the same, indicating that fibroblast contraction caused changes in a selective group of genes. The increase in c-fos mRNA during contraction of stressed collagen matrices may reflect a unique role for c-fos in mechanoregulated events at the end of wound repair.

Biomechanical Phenomena↗

PubMed1998

Gamma knife treatment of acoustic neurinoma.

The results of treatment of acoustic neurinomas using Gamma Knife radiosurgery (GKR) during a 6-year period in our center were reviewed. Since May 7, 1990, we treated 88 cases of acoustic neurinoma with GKR. During a 52-month mean follow-up period, MRI was obtained in 63 patients. Reduction in tumor size occurred in 34 (54%) cases, and another 27 (42.8%) tumors showed no change. The tumor control rate was thus 95%. Tumor size increased in 3 (4.8%) cases, but one case is still in early follow-up. Two cases were operated after GKR. Histological examination of the tumors removed at surgery 8 months after GKR were obtained. The examinations showed enlargement of nucleoli and cytoplasm and proliferation of endothelial cells due to delayed radiation changes. Post-GKR facial neuropathy was noted in 7 (8.8%) patients, of which 4 recovered during the follow-up period. The tumor volume, margin dose, number of isocenters and marginal isodose did not have any statistically significant relationship with the development of facial neuropathy. Transient trigeminal neuropathy were noted in 3 patients. Hearing was preserved in 2 of 3 hearing patients. In conclusion, our GKR results for acoustic neurinomas were very similar to the previously reported series, which makes GKR for acoustic tumors an excellent treatment modality for small- to medium-sized tumors with or without microsurgical tumor removal.

Adolescent↗

PubMed1998

Control of immune responses by gene immunization.

The use of plasmid DNA to elicit immune responses has greatly increased our ability to skew the desired immune response to a particular antigen. DNA immunization elicits potent cell-mediated responses including humoral immunity as well as cytolytic T-lymphocyte immunity. This review will first discuss the overall immune response induced by naked DNA vaccination and will then summarize recent advances in basic research on DNA immunization, which have furthered our understanding of the role of DNA as an adjuvant as well as a carrier of genetic material. Subsequently, we will consider the possible mechanisms by which DNA immunization is able to induce such immune responses and how DNA immunization may be useful in both basic science research and also in future vaccine development in various disease processes. Finally, we will examine the advantages and disadvantages of DNA vaccines as well as safety issues. In conclusion, DNA vaccination shows promise in a number of areas including infectious diseases, allergy and cancer immunotherapies.

Animals↗

PubMed1997

Pharmacokinetic monitoring and dose modification of etanidazole in the RTOG 85-27 phase III head and neck trial.

PURPOSE: To prospectively evaluate the pharmacokinetic monitoring and drug dose adjustment of Etanidazole (Eta) in patients treated on the RTOG randomized trial for Stage III and IV head and neck cancer. METHODS AND MATERIALS: From June, 1986 to October, 1991, 521 patients were randomized to conventional RT alone or RT plus Eta. The primary goal was to determine whether the addition of Eta to conventional radiation therapy improves local-regional control and tumor-free survival. Of the 264 patients who received Eta, 233 had their drug exposure calculated and the Eta dose and schedule adjusted accordingly to prevent the occurrence of serious peripheral neuropathy. Drug exposure was assessed using the area under the curve (AUC) for a single treatment that was calculated by the integral over time of the serum concentration of Eta. The total drug exposure (total-AUC) was estimated by multiplying the AUC by the number of drug administrations. RESULTS: Eighteen percent of patients developed Grade I and 6% developed Grade II peripheral neuropathy. There was no Grade 3 or 4 peripheral neuropathy. There is a trend for an increased risk of neuropathy by single dose AUC. The minimal difference in incidence of neuropathy by single-dose AUC was due to the use of dose and schedule modification for patients with the higher values. CONCLUSIONS: The pharmacokinetics investigated in this study confirm previous work that monitoring Eta levels, with dose adjustment, allows it to be used safely in the clinic. In a subset analysis there was a statistically significant improvement in local-regional control and survival rates for patients with N0 and N1 disease, that will require confirmation (14). However, the clinical efficacy of Eta in this trial proved to be of little overall benefit.

Antineoplastic Agents↗

PubMed1997

Rotavirus contains integrin ligand sequences and a disintegrin-like domain that are implicated in virus entry into cells.

Rotavirus contains two outer capsid viral proteins, the spike protein VP4 and major capsid component VP7, both of which are implicated in cell entry. We show that VP4 and VP7 contain tripeptide sequences previously shown to act as recognition sites for integrins in extracellular matrix proteins. VP4 contains the alpha2beta1 integrin ligand site DGE. In VP7, the alphaxbeta2 integrin ligand site GPR and the alpha4beta1 integrin ligand site LDV are embedded in a novel disintegrin-like domain that also shows sequence similarity to fibronectin and the tie receptor tyrosine kinase. Microorganism sequence homology to these ligand motifs and to disintegrins has not been reported previously. In our experiments, peptides including these rotaviral tripeptides and mAbs directed to these integrins specifically blocked rotavirus infection of cells shown to express alpha2beta1 and beta2 integrins. Rotavirus VP4-mediated cell entry may involve the alpha2beta1 integrin, whereas VP7 appears to interact with alphaxbeta2 and alpha4beta1 integrins.

Adenocarcinoma↗