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Biomedical subjects

F Lee

Publications and source records attributed to F Lee.

At least 91 records · Page 5Linked to original sources
PubMed1998

Development and maintenance of the gut-associated lymphoid tissue (GALT): the roles of enteric bacteria and viruses.

GALT can be subdivided into several compartments: (a) Peyer's patches (PP); (b) lamina propria (LP); and (c) intraepithelial leukocyte (IEL) spaces. The B-cell follicles of PP are quiescent in neonatal and germ-free (GF) adult mice. Germinal centers (GC), including sIgA+ blasts, appear in the B follicles of formerly GF adult mice about 10-14 days after monoassociation with various gut commensal bacteria. The GC wax and wane over about a 3-week period, although the bacterial colonizers remain in the gut at high density. Neonatal mice, born of conventionally reared (CV), immunocompetent mothers, display GC reactions in PP postweaning, although pups of SCID mothers display precocious GC reactions at about 14 days of life. Normally, gut colonization of neonates with segmented filamentous bacteria (SFB) leads to explosive development of IgA plasmablasts in LP shortly after weaning. Commensal gut bacteria and the immunocompetency of mothers also appears to control the rate of accumulation of primary B cells from "virgin" B cells in neonates. Enteric reovirus infection by the oral route can cause the activation of CD8+ T cells in the interfollicular regions of PP and the appearance of virus-specific precursor cytotoxic T lymphocytes (pCTL) in the IEL spaces. Such oral stimulation can also lead to "activation" of both CTL and natural killer (NK) cells in the IEL spaces. More normally, colonization of the gut with SFB also leads to similar activations of NK cells and "constitutively" cytotoxic T cells.

Animals↗
PubMed1998

Molecular characterization of Gluconobacter oxydans recA gene and its inhibitory effect on the function of the host wild-type recA gene.

A DNA fragment containing the recA gene of Gluconobacter oxydans was isolated and further characterized for its nucleotide sequence and ability to functionally complement various recA mutations. When expressed in an Escherichia coli recA host, the G. oxydans recA protein could efficiently function in homologous recombination and DNA damage repair. The recA gene's nucleotide sequence analysis revealed a protein of 344 amino acids with a molecular mass of 38 kDa. We observed an E. coli-like LexA repressor-binding site in the G. oxydans recA gene promoter region, suggesting that a LexA-like mediated response system may exist in G. oxydans. The expression of G. oxydans recA in E. coli RR1, a recA+ strain, surprisingly caused a remarkable reduction of the host wild-type recA gene function, whereas the expression of both Serratia marcescens recA and Pseudomonas aeruginosa recA gene caused only a slight inhibitory effect on function of the host wild-type recA gene product. Compared with the E. coli RecA protein, the identity of the amino acid sequence of G. oxydans RecA protein is much lower than those RecA proteins of both S. marcescens and Pseudomonas aeruginosa. This result suggests that the expression of another wild-type RecA could interfere with host wild-type recA gene's function, and the extent of such an interference is possibly correlated to the identity of the amino acid sequence between the two classes of RecA protein.

Amino Acid Sequence↗
PubMed1998

The role of TRUS-guided biopsies for determination of internal and external spread of prostate cancer.

This study hopes to define local extent of newly diagnosed prostate cancer by comparing sextant biopsies with transrectal ultrasound-guided diagnostic and staging biopsies. The study group consists of 110 men with sextant biopsy proven prostate cancer who presented for an opinion for prognosis and treatment options. All patients were rediagnosed and staged by transrectal ultrasound-guided and staging biopsies. Tumor diagnosis was substantiated in 94.5% (104 of 110). For the 5.4% (6 of 110) not detected by transrectal ultrasonography, review of their outside slides revealed 83.3% (5 of 6) with cancer < or =2 mm with a Gleason score of < or =6. These have the criteria of latent cancers. For the remaining 104 patients with transrectal ultrasound proven cancer, 30% (31 of 104) had extracapsular extension. Sextant and directed biopsy confirmed stage T3 in 3.8% (4 of 104). For clinical stages T1c and T2, 19% and 30%, respectively, had extracapsular extension. Perineural invasion was 1.9 times greater for directed biopsies than sextant biopsies (P < .001. The mean Gleason score was greater for directed biopsies than sextant biopsies, although no statistical difference was found (P > .05). For these 104 patients, 50% (52 of 104) had perineural invasion, of which 38.5% (20 of 52) had proven extracapsular extension. In our hands, transrectal ultrasound-directed and staging biopsies afford more substantive results than sextant biopsies for detecting extracapsular extension. For our cohort of sextant T1-T2 diagnosed cancer (n = 100), 27% were upstaged to T3-T4 by transrectal ultrasound-directed staging biopsy. Thus, transrectal ultrasound-directed staging biopsy has the ability to diagnose unsuspected extracapsular extension and objectifies prognosis and choice of definitive treatment.

Biopsy↗
PubMed1997

The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin.

Angiostatin, a potent naturally occurring inhibitor of angiogenesis and growth of tumor metastases, is generated by cancer-mediated proteolysis of plasminogen. Human prostate carcinoma cells (PC-3) release enzymatic activity that converts plasminogen to angiostatin. We have now identified two components released by PC-3 cells, urokinase (uPA) and free sulfhydryl donors (FSDs), that are sufficient for angiostatin generation. Furthermore, in a defined cell-free system, plasminogen activators [uPA, tissue-type plasminogen activator (tPA), or streptokinase], in combination with one of a series of FSDs (N-acetyl-L-cysteine, D-penicillamine, captopril, L-cysteine, or reduced glutathione] generate angiostatin from plasminogen. An essential role of plasmin catalytic activity for angiostatin generation was identified by using recombinant mutant plasminogens as substrates. The wild-type recombinant plasminogen was converted to angiostatin in the setting of uPA/FSD; however, a plasminogen activation site mutant and a catalytically inactive mutant failed to generate angiostatin. Cell-free derived angiostatin inhibited angiogenesis in vitro and in vivo and suppressed the growth of Lewis lung carcinoma metastases. These findings define a direct mechanism for cancer-cell-mediated angiostatin generation and permit large-scale production of bioactive angiostatin for investigation and potential therapeutic application.

Angiostatins↗
PubMed1997

Targeted disruption of the melanocortin-4 receptor results in obesity in mice.

The melanocortin-4 receptor (MC4-R) is a G protein-coupled, seven-transmembrane receptor expressed in the brain. Inactivation of this receptor by gene targeting results in mice that develop a maturity onset obesity syndrome associated with hyperphagia, hyperinsulinemia, and hyperglycemia. This syndrome recapitulates several of the characteristic features of the agouti obesity syndrome, which results from ectopic expression of agouti protein, a pigmentation factor normally expressed in the skin. Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R.

Animals↗
PubMed1997

Efficacy of selective unilateral exploration in hyperparathyroidism based on localization tests.

OBJECTIVES: To determine the success of unilateral exploration vs bilateral exploration for primary hyperparathyroidism and to analyze the validity of preoperative localization tests. DESIGN: Case-control study of patients who underwent surgical exploration (unilateral, n = 43; bilateral, n = 57) by 1 surgeon from January 1991 through May 1996 and who had ultrasound examination of the neck and thallium-technetium scintigraphy performed before parathyroid surgery. Initially, unilateral exploration was used sparingly, but it became the standard approach in 1994 if localization was correct. SETTING: Urban multispecialty clinic, teaching hospital. PATIENTS: One hundred consecutive patients who underwent surgical exploration for primary hyperparathyroidism. INTERVENTIONS: Ultrasonography of the neck, thallium-technetium scintigraphy, and parathyroidectomy. MAIN OUTCOME MEASURES: Imaging success, operative success, and operative time. RESULTS: In 94 patients with solitary adenomas, the adenoma was demonstrated by ultrasound scans in 66%, by thallium-technetium scintigraphy in 83%, and by either test in 87%. Correct identification by ultrasonography was 59%; by thallium-technetium scintigraphy, 75%; and together, 73%. Of 6 patients with multiple-gland disease, 2 were correctly identified by localization tests and 9 of 15 abnormal glands were demonstrated. Of the 43 unilateral explorations, 43 single adenomas and no cases of multiple-gland disease were identified; of the 57 bilateral explorations, 51 single adenomas and 6 cases of multiple-gland disease were identified. No complications occurred in either group. Hypercalcemia persisted in 3 patients who underwent bilateral exploration and recurrent hypercalcemia developed in 1 patient in each group. The average operative time for the unilateral procedure was 105 minutes, and for the bilateral procedure, 184 minutes (P < .001). Since 1994, 31 (66%) of 47 patients have had unilateral exploration based on correct localization tests. CONCLUSIONS: Unilateral exploration that is based on the results of localization tests requires less operative time and produces results similar to bilateral exploration.

Adenoma↗
PubMed1997

When the Going Gets Tough, Do the Tough Ask for Help? Help Seeking and Power Motivation in Organizations.

Individuals do not seek help, even when help is needed and available, because help seeking implies incompetence and dependence, and therefore is related to powerlessness. It was hypothesized that gender, status, and organizational norms affect the importance of maintaining and accruing power, which in turn affect help seeking behaviors. A laboratory and a field study showed that there was more help seeking between equal-status than unequal-status individuals. Further, both studies revealed that males sought more help in collective than individualistic organizational norms, though the trend was not apparent for females. These results shed light on the psychological mechanisms underlying help seeking behaviors and have practical implications for developing steps to foster help seeking in organizations. Copyright 1997 Academic Press.

Journal Article↗
PubMed1997

Effectiveness and safety of 100 consecutive parathyroidectomies.

BACKGROUND AND METHODS: In order to evaluate the indications for operation for patients with primary hyperparathyroidism, prospective information was gathered on 100 consecutively operated patients from 1991 to 1996. A standard evaluation for outcomes and patient satisfaction was instituted. Patients consisted of 73 women and 27 men. Major symptoms existed in 48 patients, and 52 patients were referred to as "asymptomatic" because they fit the National Institutes of Health Consensus Development Conference Statement with abnormal laboratory values. The pathology was 94 single adenomas, 4 double adenomas, and 2 cases of hyperplastic multiglandular disease. RESULTS: All 100 patients had abnormal parathyroids removed, resulting in normocalcemia in 97. Three patients had persistent hypercalcemia until a second operation removed additional abnormal parathyroids, resulting in normocalcemia. No operative complications or mortality occurred. Overnight stay occurred in 88 patients. During long-term follow-up of patients, only 2 developed recurrent hyperparathyroidism. When asked whether the operation improved their health, 94% of patients with major symptoms and 72% of asymptomatic patients responded affirmatively. CONCLUSION: Parathyroidectomy is an efficient and safe operation with excellent normalization of serum calcium and a high rate of patient satisfaction.

Adolescent↗
PubMed1997

Content analysis of archival data.

Content analysis can be a particularly suitable method for measuring cognitive variables from archived texts. Although content analysis has been underused by clinical psychologists, there are many benefits to this strategy. Longitudinal studies can be conducted retrospectively, the range of possible research participants can be expanded to include individuals otherwise unavailable (e.g., the famous or the dead), existing data sets can be used and reused to answer new questions, and studies across cultures and across levels of analysis (individual vs. group) can be facilitated. To illustrate the use and usefulness of content analysis to measure cognitive variables, the authors focus on the examples of causal attributions and integrative complexity, describing past research and sketching future applications to clinical research and practice.

Awareness↗
PubMed1997

Diagnosis of perinatal human immunodeficiency virus infection by polymerase chain reaction and p24 antigen detection after immune complex dissociation in an urban community hospital.

Results of polymerase chain reaction (PCR) and p24 antigen detection after immune complex dissociation (p24-ICD) were compared with antibody results after 18 months of age for human immunodeficiency virus (HIV) diagnosis in 345 prospectively followed, perinatally exposed infants. Of 59 infected and 286 uninfected infants tested at 1-6 months of age, sensitivity and specificity were, respectively, 100% and > 97% for PCR and 90% and > 97% for p24-ICD. Testing was done on > or = 2 occasions in the first 6 months of life in 43 infected infants; 77% had > or = 2 positive results with the same test. Of these infants, 68% had 2 positive p24-ICD tests. In uninfected infants, 96% had only negative tests; none had > 1 positive. By 6 months, all uninfected infants with > or = 2 PCR results could have been diagnosed. HIV status can be determined by PCR by age 6 months in most HIV-exposed infants. p24-ICD should not be used alone, because of its lower sensitivity, but may be useful in areas without advanced laboratory support.

Antigen-Antibody Complex↗
PubMed1997

Susceptibility of Pseudomonas aeruginosa of various pyocin types to the newly synthesized ampicillin derivative, N-(6,7-difluoroquinolonyl)ampicillin.

Six hundred and thirty-two isolates of Pseudomonas aeruginosa of 17 pyocin types were collected in 1993 in Taiwan. Types 1, 10, 3, 35 and 12 were the most common pyocin types identified in Taiwan with isolation frequencies of 47.3%, 24.4%, 7.6%, 3.6% and 2.2%, respectively. Several pyocin subtypes were determined. All pyocin types (one isolate of each tested) were resistant to ampicillin and nalidixic acid, but sensitive to fluoroquinolone antibiotics, such as norfloxacin and enoxacin, indicating that cross-resistance to quinolone antibiotics of nalidixic acid and fluoroquinolone derivatives has not developed. A new ampicillin derivative of 6,7-difluoroquinolonic acid, N-(6,7-difluoroquinolonyl)-ampicillin (AU-1), was synthesized by coupling ampicillin with 6,7-difluoroquinolonic acid (FP-3). Compound AU-1 was much more active than either ampicillin or FP-3 alone against all pyocin types of P. aeruginosa and induced filamentation in most growing cells.

Ampicillin↗
PubMed1997

Quantitative coronary angiography with deformable spline models.

Although current edge-following schemes can be very efficient in determining coronary boundaries, they may fail when the feature to be followed is disconnected (and the scheme is unable to bridge the discontinuity) or branch points exist where the best path to follow is indeterminate. In this paper, we present new deformable spline algorithms for determining vessel boundaries, and enhancing their centerline features. A bank of even and odd S-Gabor filter pairs of different orientations are convolved with vascular images in order to create an external snake energy field. Each filter pair will give maximum response to the segment of vessel having the same orientation as the filters. The resulting responses across filters of different orientations are combined to create an external energy field for snake optimization. Vessels are represented by B-Spline snakes, and are optimized on filter outputs with dynamic programming. The points of minimal constriction and the percent-diameter stenosis are determined from a computed vessel centerline. The system has been statistically validated using fixed stenosis and flexible-tube phantoms. It has also been validated on 20 coronary lesions with two independent operators, and has been tested for interoperator and intraoperator variability and reproducibility. The system has been found to be specially robust in complex images involving vessel branchings and incomplete contrast filling.

Algorithms↗
PubMed1997

Predominant T-cell receptor Vbeta usage of intraepithelial lymphocytes during the immune response to enteric reovirus infection.

Previous studies have found that intraepithelial lymphocytes (IEL) contain virus-specific cytotoxic T lymphocytes (CTL) that increase dramatically during the course of virus infection. In the present study, the T-cell receptor (TCR) V beta pattern used by IEL against reovirus enteric infection was investigated both in conventional and in germfree mice. IEL were isolated by a modified rapid method, and their expression of 13 TCR V betas was examined by flow cytometric analysis. The virus-specific CTL activity of each TCR V beta subset was assessed by subtraction with coated Dyna beads by a nonradioactive assay. There was a preferential perturbation of TCR V betas following virus challenge, including increases in cells expressing V beta7, -12, -14, and -17 in conventional mice and V beta2, -12, and -17 in germfree mice. In conventionally reared mice, IEL maintained and restimulated in culture had a preferential use of TCR V beta9, -12, and -17. TCR V beta2 and -17 subfamilies were found amplified in all conditions. Furthermore, TCR V beta12 and -17 accounted for 37 and 77% of the virus-specific CTL activity, respectively, after in vitro restimulation. This study provides evidence that virus-specific CTL activity may be due to the oligoclonal expansion of TCR V beta subfamilies in IEL. Our findings suggest that in vivo infection selectively presents few T-cell epitopes and that the correct identification of these T-cell epitopes would increase the likelihood of success when designing subunit vaccines.

Animals↗
PubMed1997

Human androgen receptor expression in prostate cancer following androgen ablation.

OBJECTIVE: Metastatic prostate cancer kills patients because their tumor cells fail to respond to combined androgen blockade (CAB) or respond and then relapse. To understand the molecular basis of androgen-insensitive growth of prostate tumor cells, we evaluated changes in human androgen receptor gene (hAR) mRNA levels in patients with prostate cancer treated with CAB. METHODS: The study was carried out using quantitative reverse-transcriptase polymerase chain reaction analysis. The level of hAR mRNA were compared to serum prostate-specific antigen and the mutant status of p53 in the tumor. RESULTS: hAR was expressed in 44 of 46 tumors from untreated patients, as opposed to 30 of 45 from those who had received CAB (p = 0.001). These 30 were from 8 of 9 stage D patients and from 22 of 36 patients on downsizing CAB therapy prior to radical prostatectomy. Expression was most often seen in high stages (56% of stage B vs. 89% of stage D) and high grades (52% of Gleason 3-7 vs. 92% of Gleason 8-10, p = 0.015). No tumor with a missense p53 mutation had hAR expression following CAB. Twenty-two patients following CAB were found to have undetectable serum prostate-specific antigen levels, while their tumor expressed hAR. CONCLUSIONS: hAR expression after CAB is seen preferentially in high-grade, high-stage tumors, the type of prostate carcinomas that fail to have a durable remission. Undetectable serum prostate-specific antigen from tumors that remain hAR positive may predict relapse after hormonal ablative therapy.

Androgen Antagonists↗