Biomedical subjects

F Lee

Publications and source records attributed to F Lee.

At least 127 records · Page 7Linked to original sources

PubMed1995

Prostate cancer: US-guided percutaneous cryoablation. Work in progress.

PURPOSE: To present early results of cryosurgical ablation of prostate cancer with an ultrasound-guided percutaneous technique. MATERIALS AND METHODS: Cryosurgery was performed in 210 patients; near complete 3- and 6-month follow-up data were available for 130. Androgen ablation therapy was used to decrease the size of the prostate gland for optimal freezing. Prostate-specific antigen (PSA) and prostatic biopsy studies were performed at 3, 6, and 12 months. RESULTS: Gland volume decreased from 29 cm3 +/- 14.1 to 20.4 cm3 +/- 8.4 (P < .0001) after androgen ablation. Rates of positive biopsy findings at 3, 6, and 12 months were 7.7%, 3.3%, and 2.3%, respectively. Serious complications were minimal and included no deaths, urethrorectal fistulas in five patients, and total incontinence in three. Mean PSA levels decreased from 12.6 +/- 16.1 preoperatively to 0.35 +/- 0.75 at 3 months, 0.54 +/- 1.1 at 6 months, and 0.43 +/- 0.78 at 12 months (persistent cancers excluded). CONCLUSION: These preliminary results demonstrate that cryosurgery can cause necrosis of prostate cancer. Long-term results and randomized trials are necessary to determine if this means longer disease-free intervals and increased patient survival compared with results of current therapeutic methods.

Aged↗

PubMed1995

A new approach to the study of haematopoietic development in the yolk sac and embryoid bodies.

To understand the mechanisms that control the differentiation of uncommitted mesoderm precursors into haematopoietic stem cells (HSCs) and the activation of haematopoiesis, we conducted a study to identify genes expressed at the earliest stages of both in vivo and in vitro haematopoietic development. Our strategy was to utilize Differential Display by means of the Polymerase Chain Reaction (DD-PCR) to compare patterns of gene expression between mRNA populations representing different levels of haematopoietic activity obtained from the mouse embryo, embryoid bodies (EBs) and mouse cell lines. We report the molecular cloning of two groups of genes expressed in the yolk sac: a group of genes expressed in the day-8.5 yolk sac at higher levels than in the day-8.5 embryo proper and up-regulated during EB development, and another group of day-8.5 yolk sac genes not expressed in the day-8.5 embryo proper or in EBs. Specifically, we describe the molecular cloning of the first nucleobase permease gene to be found in vertebrates, yolk sac permease-like molecule 1 (Ysp11). The Ysp11 gene has the unique property of encoding both intracellular, transmembrane and extracellular protein forms, revealing novel aspects of nucleotide metabolism that may be relevant during mammalian development.

Amino Acid Sequence↗

PubMed1995

Transgene inheritance and retroviral infection contribute to the efficiency of gene expression in solid tumors inoculated with retroviral vector producer cells.

One strategy to achieve efficient gene delivery into brain tumors employs the stereotactic implantation of fibroblasts that express a foreign gene and produce a retroviral vector bearing that gene. Another method involves the grafting of fibroblasts genetically engineered to produce a foreign gene product of interest. It is not clear to what extent retrovirus production in vivo provides an advantage over the grafting of genetically engineered cells for the purpose of achieving transgene expression. These two methods of gene delivery were compared in vivo by using the following cell lines: CRIP-MFG-LacZ cells, which express the lacZ gene and produce retrovirus vectors that bear this gene, and CRIP-LacZ cells, which express the lacZ gene, but do not produce retrovirus. Gene delivery was assessed in C6 gliomas established in the righ frontal lobe of athymic mice. CRIP-MFG-LacZ or CRIP-LacZ cells were inoculated stereotactically into these tumors. When CRIP-MFG-LacZ cells were used, a relatively elevated level of lacZ gene expression was present in cells scattered throughout the tumor. Using a computerized imaging system, this expression occurred in approximately 10% of the tumor area at 1 week, 42% at 2 weeks, and 32% at 3 weeks. In contrast, with CRIP-LacZ cells, lacZ gene expression was much weaker and occurred in a more focal area within the tumor. This expression occupied approximately 5% of the tumor area at 1 and 2 weeks and had almost disappeared at 3 weeks. In both cases there was no notable expression of the transgene in normal brain cells. In conclusion, transgene expression in brain tumors was achieved in more cells, at higher levels, and for longer time periods with retroviral vector-producing cells than with genetically engineered fibroblasts. This efficiency of gene delivery likely results from direct in situ delivery of the transgene to tumor cells with subsequent inheritance of the reporter gene to progeny tumor cells.

3T3 Cells↗

PubMed1994

Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma.

Representational difference analysis was used to isolate unique sequences present in more than 90 percent of Kaposi's sarcoma (KS) tissues obtained from patients with acquired immunodeficiency syndrome (AIDS). These sequences were not present in tissue DNA from non-AIDS patients, but were present in 15 percent of non-KS tissue DNA samples from AIDS patients. The sequences are homologous to, but distinct from, capsid and tegument protein genes of the Gammaherpesvirinae, herpesvirus saimiri and Epstein-Barr virus. These KS-associated herpesvirus-like (KSHV) sequences appear to define a new human herpesvirus.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Cost-effective prostate cancer detection. Reduction of low-yield biopsies. Investigators of the American Cancer Society National Prostate Cancer Detection Project.

BACKGROUND: In hopes of limiting low-yield prostate biopsies, results of digital rectal examination (DRE), transrectal ultrasound (TRUS), prostate specific antigen (PSA) and age-related PSA values, gland-volume-adjusted PSA levels, and longitudinal PSA changes were analyzed to identify their cost-effectiveness as prognostic indicators in screening, biopsy, and follow-up of patients with prostate cancer. METHODS: Twenty-nine hundred men with complete data sets from an initial cohort of 2999 men with an annual follow-up for up to 5 years were examined. Intrapatient PSA and gland-volume variability, optimal PSA operating points (o.p.), and test performance scores were determined for each parameter. Decision analysis was then applied retrospectively to each parameter to determine the cancer detection yield, biopsy requirements, and costs for commonly used detection strategies. RESULTS: For the initial screening decision, the optimal PSA o.p. was 3.0 ng/ml but increased to 5.0 ng/ml in combination with DRE, whereas age-related PSA performed no better than did PSA. The mean intrapatient variability in TRUS gland volume (+5.5 cc) relative to mean volume (34 cc) was 16%, which was less than the 28% (0.64/2.3 ng/ml) relative variability for PSA. For biopsy decisions, using PSA density (PSAD) with a level of 0.12 ng/ml/cc there was no significant difference in accuracy compared with the systematic biopsy of all patients with elevated PSA or age-related PSA levels. Rather than perform systematic biopsy on all patients with PSA levels greater than 4 ng/ml, decision analysis showed that a 16-55% reduction in biopsies could be achieved with a respective cancer loss of 4-25% by limiting biopsy to patients with an increased PSAD level and/or abnormal results of DRE. Using age-related PSA criteria in combination with DRE reduced biopsies by 12% but resulted in minimal cost reductions. The greatest biopsy reduction relative to cancer yield and lowest cost per cancer detected occurred with PSAD-driven biopsy strategies. During follow-up, longitudinal changes in absolute PSA and PSAD levels were significantly better (P < 0.05) than the percentage change in PSA levels per year. CONCLUSIONS: Cost-effective prostate cancer detection with PSA as a parameter is better achieved if screening and biopsy decisions are not linked intimately. A tailored-biopsy approach for patients with disproportionately elevated PSA levels of suspicious DRE results in the greatest biopsy reduction by selecting lower risk groups for more conservative follow-up.

Age Factors↗

PubMed1994

Relative sensitivity and specificity of serum prostate specific antigen (PSA) level compared with age-referenced PSA, PSA density, and PSA change. Data from the American Cancer Society National Prostate Cancer Detection Project.

BACKGROUND: Different indexes that may enhance the early detection capability of prostate specific antigen (PSA) have been proposed. In addition to the indexes relating to the normal PSA level, there are data suggesting the usefulness of the PSA level relative to prostate gland volume (PSA density), age-referenced PSA level, and PSA change. Little research comparing the sensitivity and specificity of these measures in the same population has been reported. METHODS: All subjects were participants in the American Cancer Society National Prostate Cancer Detection Project. Specificity was studied in 2011 men without prostate cancer, and sensitivity was determined for 171 men with prostate cancer. RESULTS: Prostate specific antigen change showed the highest specificity (96.4%), and PSA density the lowest (85.3%). The most sensitive index was PSA density, which was positive for 74.7% of the 171 cases of known cancer. A PSA change of more than 0.75 ng/ml per year was the least sensitive index (54.8%). Sensitivity and specificity varied in a narrow range. Improved performance in specificity was achieved only with the loss of sensitivity. CONCLUSIONS: None of the alternative indexes commonly used in general early detection practice demonstrated particular advantage when compared with the normal PSA concentration, defined as no more than 4.0 ng/ml.

Adult↗

PubMed1994

The E2A and tal-1 helix-loop-helix proteins associate in vivo and are modulated by Id proteins during interleukin 6-induced myeloid differentiation.

The immunoglobulin enhancer-binding proteins, E12 and E47, encoded by the E2A gene belong to the basic helix-loop-helix (bHLH) family of regulatory proteins and act as transcriptional activators. In addition to their critical role in B-lymphocyte development, the E12 and E47 proteins have been implicated in the induction of myogenesis as heterodimeric partners of myogenic bHLH proteins, MyoD and myogenin. Here we demonstrate that the E2A proteins form heterodimers with the bHLH oncoprotein tal-1 in myeloid and erythroid cells and that these heterodimers specifically bind to the CANNTG DNA motif. Heterodimerization with tal-1 represses transactivation by E47 and could function to prevent the expression of immunoglobulin genes in cells other than B lymphocytes. DNA binding by E2A-tal-1 heterodimers in the M1 mouse myeloid cell line is abrogated upon terminal macrophage differentiation induced by the cytokine interleukin 6. The loss of E2A-tal-1 DNA binding is correlated with elevated expression of mRNA encoding the dominant negative HLH proteins, Id1 and particularly Id2. Moreover, recombinant Id proteins inhibit the E2A-tal-1-specific DNA binding activity from undifferentiated M1 cells. These results suggest that E2A-tal-1 heterodimers may play a role in preventing terminal differentiation in the myeloid lineage and provide a possible explanation for oncogenic transformation induced by ectopic tal-1 expression in acute T-cell lymphoblastic leukemias.

Animals↗

PubMed1994

p53 in prostate cancer: frequent expressed transition mutations.

BACKGROUND: Carcinoma of the prostate is the second most common cause of cancer deaths in men. Little is known about the pathogenesis of this disease and the molecular genetic events that contribute to its development. Molecular studies have begun to reveal biologic characteristics of this disease, notably, the loss of genetic material as determined by studies of restriction fragment length polymorphism, oncogene activation, and production and response to growth factors. PURPOSE: Our goal was to characterize p53 gene mutations in human carcinoma of the prostate and to analyze base-pair changes within the coding regions of p53 mRNA (exons 4 through 11). METHODS: Forty-four prostate tissue specimens and four metastatic lesions were obtained from 48 prostate carcinoma patients who had surgical resection. RNA was either immediately extracted or the specimens were snap-frozen in liquid N2 and stored at -70 degrees C until used. Total RNA was extracted from tumor specimens. Expression of p53 was analyzed by polymerase chain reaction (PCR) analysis of mRNA (RNA/PCR). Following confirmation of the RNA/PCR products by Southern blotting, quantitation of message levels was performed by laser densitometry. Absolute area integrations of the curves representing each tissue were then compared after adjustment for the housekeeping gene c-N-ras. Two overlapping regions (exons 4-6 and 6-11) were examined by a nonisotopic PCR single-strand conformation polymorphism (SSCP) analysis system. All specimens displaying SSCP abnormalities were sequenced in both directions to confirm the findings. RESULTS: Of the 48 prostate specimens, three (6%) (two primary and one metastatic) displayed nearly undetectable expression of p53 mRNA (samples PS-70, L113, and PS-95) and 17 (35%) of 48 expressed mutant p53 mRNA encoding amino acid substitutions within exons 4-11 (14 of 17) and/or deletions within the p53 transcripts (three of 17). Overall, the frequency of p53 gene abnormalities that would result in altered protein expression was 20 (42%) of 48 in the tissue samples from prostate carcinoma patients. Nucleotide base-pair transitions of A-->G or T-->C were the most frequent. CONCLUSIONS: p53 mutations are common in prostate cancer. The patterns of p53 gene mutations are dramatically different from data obtained on other cancers and indicate the possible involvement of a carcinogenic agent(s). IMPLICATIONS: Further studies are required to determine the biologic role of p53 gene alterations in the development and progression of this disease and to determine whether p53 mutations can be useful as prognostic markers or for the selection of better treatments for prostate cancer patients.

Base Sequence↗

PubMed1994

The development of the immune system--importance in the ascertainment of immunophenotypic changes in perinatal HIV infection.

Evidence is presented that the percentage and number of some subsets of T and B cells in normal children and adults vary greatly from those in fetal life and throughout the first few years after birth, and less so during adolescence and adulthood. Depending then on the age at which immunological studies are performed, as well as whether the HIV infection occurs in utero, at birth, or postnatally, values obtained by immunophenotypic analyses of differentiating or mature immunocytes will vary greatly. A concerted effort needs to be made to measure different developmental and activation immunophenotypic markers, from birth on, in premature and full-term infants of varying socioeconomic and ethnic background. Results from such studies should improve our ability to determine the timing of HIV infection, to obtain earlier guidelines for prophylaxis or treatment of the virus or of opportunistic infections, as well as to improve prognostic capabilities in perinatal HIV infection.

Fetus↗

PubMed1994

Subpopulations of T and B cells in perinatally HIV-infected and noninfected age-matched children compared with those in adults.

Peripheral blood mononuclear cells were quantified for the subsets of CD4, CD8, and CD19 lymphocytes by using CD45RA (2H4), CD29(4B4), CD57, CD5, CD10, Leu8, HLA-DR, and TCR gamma delta-1 monoclonal antibodies and dual color immunofluorescence. A comparative analysis of lymphocyte subpopulations was made among 52 HIV-infected and 50 age-matched control children and 30 HIV-seropositive and 27 negative control adults. A significant decrease in the CD4+CD45RA+ "naive" cells was much more marked in HIV-infected children than in HIV-infected adults. A significant percentage increase in the CD4+CD29+ "memory" cells was observed in HIV-infected children but not in infected adults; however, the absolute numbers were usually decreased in all age groups. The mean percentage and absolute numbers of CD4+CD7+ and CD4+Leu8+ cells were decreased in HIV-infected children, although usually not significantly. The CD3+TCR gamma delta-1+ did not show any change in the infected children tested. The mean percentage and absolute number of the CD8+HLA-DR+ cells increased significantly in HIV-infected persons of all ages. The CD8+CD57+ cells were increased in percentage and absolute number in HIV-infected children ages 1-4 and 4-8 years. In the adults, no change was noted in either the percentage or absolute number of CD19+CD5+ B cells, a finding similar to that noted in HIV-infected children above 1 year of age. Although adults showed a significant decrease in both percentage and numbers of CD5- B cells, an increase was noted in the 7- to 12-month-old HIV-infected children. The CD19+CD10+ cells showed a slight but significant decrease in the youngest age group and a significant increase in the older age groups of HIV-infected children. These findings indicate that several lymphocyte subpopulations are altered differentially during HIV infection in children of varying ages and in adults.

Adult↗

PubMed1994

The gut-brain peptide cyclo(His-Pro) is secreted in a pulsatile fashion in fasting humans.

Histidyl-proline diketopiperazine (CHP) is a cyclic dipeptide that is found in many animal tissues, most notably brain and gut. It has been found to have a variety of biologic actions and has been postulated to play a role in appetitive behavior and energy metabolism. This study was conducted in order to characterize the secretory pattern of CHP during a 24 h fast. Four subjects (2 obese and 2 lean) were studied during the latter 24 h of a 36 h fast. Blood was sampled every 10-15 min and assayed for CHP concentration using a specific radioimmunoassay. Analysis revealed that circulating CHP oscillates in humans and that diurnal variation occurred but only in the obese subjects.

Adult↗

PubMed1994

Cytokines in the central nervous system: expression of macrophage colony stimulating factor and its receptor during development.

To investigate the potential role of cytokines in the development of the central nervous system, we analyzed the production of cytokine mRNA transcripts by S1-nuclease protection analysis in the brains of Swiss-Webster mice during fetal development and after birth. Cytokines studied were interleukin (IL)-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, macrophage-colony stimulating factor (M-CSF), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and leukemia inhibitory factor (LIF). Only mRNA transcripts for M-CSF were found to be produced constitutively in normal brain tissue. These transcripts were detected continuously from embryonic day (ED) 13 through adulthood. Transcripts encoding the M-CSF receptor (c-fms) were also detected at all of these time points. Despite identification of M-CSF transcripts in the brains of normal mice during development and M-CSF protein in cell cultures, neuropathological examination of the brains of op/op mice, a naturally occurring mouse mutant defective in the production of functional M-CSF, showed no cytoarchitectural abnormalities.

Age Factors↗

PubMed1994

Prospects for reform of hospital fees in sub-Saharan Africa: a case study of Niamey National Hospital in Niger.

Hospital finance in developing countries has attracted increasing attention in recent years as economists and health planners have examined whether financial reforms will make public hospitals more financially autonomous and consequently reduce (or limit the increase in) their share of government health budgets. This paper presents estimates of the effects of some reforms of hospital user fees on total hospital revenue and on the amount of fees paid by patients in various payor categories. The reforms include special fees for non-referred patients and changes in exemptions for some categories of patients and types of care. The estimates show that doubling fees for non-referred patients increases revenue more than charging them prices equal to operating costs, because current fees are not uniformly less than operating costs. Eliminating exemptions can be as important as changing fees. For example, eliminating exemptions for surgery and inpatient diagnostic exams increases the percentage of operating costs recovered by the same amount as doubling prices for non-referred patients in estimates with an elasticity of demand equal to zero.

Fees, Medical↗

PubMed1994

Oncostatin M stimulates proliferation in B9 hybridoma cells: potential role of oncostatin M in plasmacytoma development.

Oncostatin M was found to stimulate the IL-6-addicted hybridoma line B9. Leukaemia inhibitory factor did not stimulate proliferation of this line. Both of these factors bind to the gp130 of the IL-6 receptor. In another cell line that is stimulated by LIF (DA.1), neither IL-6 nor oncostatin M stimulated proliferation. Previously it had been thought that the gp130 alone is sufficient to bind ligand and transduce signal and that oncostatin M could bind to and activate the LIF receptor, but these data show this is not always the case. Mice primed with Pristane were found to have IL-6 in their sera and peritoneal fluid only at a few time points following Pristane treatment; this was determined by IL-6-specific ELISA. When the same samples were analysed on IL-6-addicted B9 cells, stimulatory activity was found at all time points. When the Pristane-primed samples were assayed for oncostatin M activity in the A375 melanoma assay, there was oncostatin M activity at various time points. IL-6 did not have activity on the A375 cells. These data indicate that oncostatin M play a role in the generation of plasmacytoma in vivo.

Animals↗

PubMed1994

A semiquantitative dietary history questionnaire for Chinese Americans.

An 84-item, semiquantitative dietary history questionnaire was developed for epidemiologic studies of diet and diseases in Chinese Americans. The questionnaire is a 30-minute, face-to-face administered instrument designed especially for assessing mixed dishes; it consists of a food list and requires information on frequency of consumption and portion estimation. A nutrient database was compiled from many sources, but mostly from US Department of Agriculture publications. The relative validity of this food frequency questionnaire was tested among 74 Chinese women between the ages of 30 and 60 years living in the San Francisco Bay area against a 1-day recall deemed a typical day's diet. Correlation coefficients of nutrients from both methods ranged from 0.2 for total fat to 0.7 for calcium and were all statistically significant at less than the 0.001 level. Agreement between these two methods was assessed by the percentage of misclassification of quartile distributions. Around 10% were grossly misclassified and 50% were correct estimates of intake in the same highest quartile, while 73% were correctly placed in the two highest quartiles. This food frequency questionnaire can reasonably estimate the usual dietary intakes among Chinese Americans for epidemiologic studies, but further validation would be needed.

Adult↗

PubMed1994

Varicella in children with perinatally acquired human immunodeficiency virus infection.

Thirteen children with human immunodeficiency virus infection acquired perinatally and with varicella were identified. Clinical and epidemiologic information, including the use of varicella immune globulin and acyclovir, was obtained and testing for antibodies to varicella-zoster virus was done. The 13 children infected with human immunodeficiency virus had an uncomplicated clinical course, and many had a significant antibody response to varicella-zoster virus.

Acyclovir↗

PubMed1994

Characteristics of prostate cancer detected in the American Cancer Society-National Prostate Cancer Detection Project.

The American Cancer Society-National Prostate Cancer Detection Project is a prospective, comparative study of a cohort of 2,999 men 55 to 70 years old not suspected on entry of having prostate cancer. A total of 164 prostate cancers is available from this project for analysis. A small proportion of tumors detected were advanced in terms of the clinical stage at diagnosis. Cancer detected by digital rectal examination tended to be more advanced than that found on the basis of only transrectal ultrasound or prostate specific antigen (PSA). A large proportion of patients received curative therapy involving radical prostatectomy in 67.1% and radiotherapy in 18.3%. Of 103 men presumed to have organ confined disease and treated by prostatectomy 64 (37.9%) actually had locally extensive cancer pathologically. PSA level and PSA density were associated with the detection of organ confined cancer but several advanced tumors had PSA levels in the normal range. Age referenced PSA, compared to conventional standards, demonstrated lower sensitivity to cancer with little improvement in specificity. The disease resulting from this multimodality detection effort represented a spectrum of pathological conditions. Further followup and evaluation are needed to determine whether these benefits are reflected in long-term mortality and survival experience.

Aged↗

PubMed1994

Prediction of antisocial behavior in attention-deficit hyperactivity disorder boys from aggression/defiance scores.

OBJECTIVE: To predict teen-age arrests from measures of childhood defiance in attention-deficit hyperactivity disorder (ADHD) boys. METHOD: Defiance ratings that were independent of hyperactivity were obtained on two groups of ADHD boys. Official arrest data obtained on all subjects 9 years later were used as the outcome measure. RESULTS: ADHD boys with high defiance ratings had significantly higher felony offender rates than did boys with low ratings. However, the ADHD boys with low ratings had significantly higher felony offender rates than did normal control boys. CONCLUSIONS: Clinicians and parents should be alerted to the fact that minor antisocial features in ADHD boys, such as defiance, signal an increased risk for later serious antisocial behavior. However, they should not be misled by the absence of defiance in ADHD boys to think that these boys are not at risk for serious antisocial behavior (arrests for serious criminal behavior) later in life.

Adolescent↗