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Biomedical subjects

F Lee

Publications and source records attributed to F Lee.

At least 73 records · Page 4Linked to original sources
PubMed2000

Patient-reported complications after cryoablation therapy for prostate cancer.

To define the patient-reported complications after cryoablation therapy for prostate cancer and to compare these results to previously published patient-reported complications for radical prostatectomy and external beam irradiation. A questionnaire similar to previously published patient-reported complication studies was sent to the first 290 patients treated by cryoablation therapy at our Institution. The questionnaire was returned by 267 patients. Forty-four patients were excluded from analysis because of prior irradiation, transurethral prostatectomy, or cryoablation, resulting in a study group of 223 patients. Of the 208 patients with good urinary control preoperatively, 9 (4.3%) patients used incontinence pads after cryoablation. Seven of the 8 patients who used one pad daily reported leakage of only a few drops. Impotency, defined as an inability to obtain erections adequate for vaginal penetration, occurred in 85% of men who were potent preoperatively. Urethrorectal fistula occurred in 1 patient (0.4%). Bladder outlet obstruction caused by stricture of sloughed necrotic prostatic tissue required dilation or transurethral resection in 10% of patients. Scrotal swelling, penile tingling, and pelvic pain occurred in 18, 15, and 12% of patients, respectively; typically, these resolved spontaneously within 3 months. Patient-reported complications for cryoblation compared favorably to those reported for radical prostatectomy and external beam irradiation. Patient satisfaction was high; 96% of patients reported that they would choose cryosurgery as a treatment option again.

Aged↗
PubMed1999

Discovery and structure-activity relationships of imidazole-containing tetrahydrobenzodiazepine inhibitors of farnesyltransferase.

2,3,4,5-Tetrahydro-1-(imidazol-4-ylalkyl)-1,4-benzodiazepines were found to be potent inhibitors of farnesyltransferase (FT). A hydrophobic substituent at the 4-position of the benzodiazepine, linked via a hydrogen bond acceptor, was important to enzyme inhibitory activity. An aryl ring at position 7 or a hydrophobic group linked to the 8-position through an amide, carbamate, or urea linkage was also important for potent inhibition. 2,3,4, 5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2-(t rifluo romethoxy)benzoyl]-1H-1,4-benzodiazepine (36), with an FT IC(50) value of 24 nM, produced 85% phenotypic reversion of Ras transformed NIH 3T3 cells at 1.25 microM and had an EC(50) of 160 nM for inhibition of anchorage-independent growth in soft agar of H-Ras transformed Rat-1 cells. Selected analogues demonstrated ip antitumor activity against an ip Rat-1 tumor in mice.

3T3 Cells↗
PubMed1999

M-Ras, a widely expressed 29-kD homologue of p21 Ras: expression of a constitutively active mutant results in factor-independent growth of an interleukin-3-dependent cell line.

M-Ras, a recently identified homologue of p21 Ras, is widely expressed, with levels of the 29-kD protein in spleen, thymus, and NIH 3T3 fibroblasts equaling or exceeding those of p21 Ras. A G22V mutant of M-Ras was constitutively active and its expression in an interleukin-3 (IL-3)-dependent mast cell/megakaryocyte cell line resulted in increased survival in the absence of IL-3, increased growth in IL-4, and, at high expression levels, in factor-independent growth. Expression of M-Ras G22V, however, had a negative effect on growth in the presence of IL-3, suggesting that M-Ras has both positive and negative effects on growth. Expression of M-Ras G22V in NIH-3T3 fibroblasts resulted in morphological transformation and growth to higher cell densities. M-Ras G22V induced activation of the c-fos promoter, and bound weakly to the Ras-binding domains of Raf-1 and RalGDS. Expression of a mutant of M-Ras G22V that was no longer membrane-bound partially inhibited (40%) activation of the c-fos promoter by N-Ras Q61K, suggesting that M-Ras shared some, but not all, of the effectors of N-Ras. An S27N mutant of M-Ras, like the analogous H-Ras S17N mutant, was a dominant inhibitor of activation of the c-fos promoter by constitutively active Src Y527F, suggesting that M-Ras and p21 Ras shared guanine nucleotide exchange factors and are likely to be activated in parallel. Moreover, M-Ras was recognized by the monoclonal anti-Ras antibody Y13-259, commonly used to study the function and activity of p21 Ras. Mammalian M-Ras and a Caenorhabditis elegans orthologue exhibit conserved structural features, and these are likely to mediate activation of distinctive signaling paths that function in parallel to those downstream of p21 Ras.

3T3 Cells↗
PubMed1999

Characterization of the cytoplasmic domain of interleukin-13 receptor-alpha.

Interleukin (IL)-13 and IL-4 are pleiotropic immunoregulatory cytokines that share many overlapping biological properties reflecting the fact that both can utilize a receptor complex composed of the IL-4 receptor-alpha (IL-4Ralpha) chain and the IL-13Ralpha chain. The cytoplasmic domain of the IL-13Ralpha is 60 amino acids long and is essential for IL-13-dependent growth. It contains a Pro-rich domain in the membrane-proximal region and two Tyr residues. Here we show that a truncated IL-13Ralpha, lacking the 38 carboxyl-terminal residues but retaining the Pro-rich region, can support IL-13-dependent proliferation, although with reduced efficiency. A Y402F mutant of the cytoplasmic domain of IL-13Ralpha supported normal IL-13-induced growth. However, tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3), which we show is induced by IL-13 and IL-4 in cells that express the IL-13Ralpha, was significantly reduced. The cytoplasmic domain of IL-13Ralpha was constitutively associated with STAT3, Tyk2, and Janus kinase 1 (JAK1). IL-13-induced tyrosine phosphorylation of IL-13Ralpha in vivo could not be detected using anti-Tyr(P) antibodies. A glutathione S-transferase fusion protein of the cytoplasmic domain of IL-13Ralpha was phosphorylated on tyrosine in vitro by JAK1, JAK3, and Tyk2, although the tyrosine phosphorylation events mediated by Tyk2 and JAK3 were not detectable using anti-phosphotyrosine antibodies. These data, together with the demonstration that IL-13Ralpha associates constitutively with Tyk2 and that Tyr-402 is involved in IL-13-induced phosphorylation of STAT3, suggest that the latter is mediated by Tyk2. Tyrosine phosphorylation of STAT3, which was not necessary for IL-13-induced proliferation, may account for some of the effects of IL-4 and IL-13 on the function of their targets.

Base Sequence↗
PubMed1999

Measuring treatment outcomes and client satisfaction in a partial hospitalization program.

Mental health practitioners are increasingly being called on to evaluate the effectiveness of the treatment they provide. The partial hospitalization component of the mental health industry also has felt this call for outcome research. This article presents the results of one program's attempts to answer that call through an assessment of treatment outcome and client satisfaction at a partial hospitalization program. Participants (N = 287) were evaluated at admission, discharge, and 3-month follow-up. The article outlines the procedures used for assessment and uses the results as an example of the type of data that can be obtained through outcomes measurement. The article is intended to provide an example of program evaluation that is easy and inexpensive to administer.

Adolescent↗
PubMed1999

Cryosurgery for prostate cancer: improved glandular ablation by use of 6 to 8 cryoprobes.

OBJECTIVES: To describe and assess the efficacy for increased glandular destruction by using 6 to 8 cryoprobes in place of the traditional 5 probes. METHODS: In April 1996, a revised method for cryosurgery was begun that uses 6 to 8 cryoprobes, and by July 1997, 81 men had been treated. This group was compared retrospectively to our last 82 cases done before April 1996 using 5 cryoprobes. All cases were consecutive. To ensure that the groups were similar, comparison was performed of entrance prostate-specific antigen (PSA), clinical stage, and Gleason score. Six months after cryosurgery, PSA and residual epithelial acini were compared between the two groups. RESULTS: The two groups were comparable for all the above parameters (P >0.05). The degree of overall glandular kill was greater for the 6 to 8-probe method (P = 0.023). Complete glandular ablation for the 5-probe and 6 to 8-probe methods was 39% and 53%, respectively, and the difference was not significant (P = 0.072). However, when one combined the complete glandular ablation group with the none to few residual acini group, 67.5% for the 5-probe method and 88.9% for the 6 to 8-probe method, a significant difference was found (P = 0.001). The odds of having many remaining acini versus having none to few were 3.5 times greater in the 5-probe group than in the 6 to 8-probe group. The mean and median PSA for the 5- and 6 to 8-probe groups were 0.19 and 0.1 versus 0.11 and 0.07 ng/mL, respectively, a significant difference (P = 0.02). No difference was found in rates of tumor persistence or complications. CONCLUSIONS: A revised method for cryosurgery using 6 to 8 cryoprobes has proved to be more effective for near-glandular ablation than the traditional 5-probe method. It was easily applied, had a wide margin of safety, and even shortened learning time. These innovations have permitted a closer approach to the goal of complete glandular destruction.

Cryosurgery↗
PubMed1999

Patient-reported complications after cryoablation therapy for prostate cancer.

OBJECTIVES: To define the patient-reported complications after cryoablation therapy for prostate cancer and to compare these results to previously published patient-reported complications for radical prostatectomy and external beam irradiation. METHODS: A questionnaire similar to previously published patient-reported complication studies was sent to the first 290 patients treated by cryoablation therapy at our institution. The questionnaire was returned by 267 patients. Forty-four patients were excluded from analysis because of prior irradiation, transurethral prostatectomy, or cryoablation, resulting in a study group of 223 patients. RESULTS: Of the 208 patients with good urinary control preoperatively, 9 (4.3%) patients used incontinence pads after cryoablation. Seven of the 8 patients who used one pad daily reported leakage of only a few drops. Impotency, defined as an inability to obtain erections adequate for vaginal penetration, occurred in 85% of men who were potent preoperatively. Urethrorectal fistula occurred in 1 patient (0.4%). Bladder outlet obstruction caused by stricture or sloughed necrotic prostatic tissue required dilation or transurethral resection in 10% of patients. Scrotal swelling, penile tingling, and pelvic pain occurred in 18%, 15%, and 12% of patients, respectively; typically, these resolved spontaneously within 3 months. CONCLUSIONS: Patient-reported complications for cryoablation compared favorably to those reported for radical prostatectomy and external beam irradiation. Patient satisfaction was high; 96% of patients reported that they would choose cryosurgery as a treatment option again.

Aged↗
PubMed1999

Cytokine production by CD4+ T-cells responding to antigen presentation by melanoma cells.

Melanoma cells are unusual because, unlike most epithelial tumours, constitutive expression of HLA class II antigens is common. We have previously demonstrated that a peptide-specific CD4+ T-cell clone proliferates briskly in response to peptide and HLA class II expressing melanoma cell lines derived from metastases. Here we demonstrate that these CD4+ T-cells secrete large amounts of interferon-gamma (IFNgamma) and interleukin-10 (IL10), and insignificant quantities of IL2 or IL4, in response to peptide presentation by both melanoma and autologous B-cells. T-cells produced more IL10 when responding to peptide presentation by melanoma cells compared with B-cells, and less IFNgamma (P<0.01). Addition of IL12 did not alter the cytokines produced but increased the T-cell production of both, especially the production of IL10 in response to peptide presentation by melanoma cells. Our data suggest that differential cytokine production by CD4+ T-cells in response to peptide presentation by HLA class II expressing tumour cells may contribute to tolerance to tumour antigens.

Antigen-Presenting Cells↗
PubMed1999

Descriptive study of sledding injuries in Canadian children.

OBJECTIVES: (1) To describe the characteristics of sledding injuries presenting to a pediatric emergency department and (2) To describe the sledding environment that leads to childhood sledding injuries. SETTING: A pediatric hospital emergency department in Ottawa, Canada and identified sledding sites in the region. METHODS: All patients less than 18 years with sled related injuries were included. Questionnaires were completed gathering information on the sled operator, the sled, the sledding site, and the injury. Site visits were made to designated and non-designated sledding hills in the Ottawa region to record data regarding sled operators, sleds, and the sledding environment. RESULTS: Ninety-five patients were identified with sledding injuries and 81 (85%) completed the questionnaire. The mean age was 9.9 years (range 8 months to 17 years). The majority were male (63%). Most injuries occurred on non-designated sledding hills in the community (70%). Mild to moderate injuries were most common, however nine patients (11%) were admitted to hospital. Fifty-one per cent had adult supervision at the time of injury compared with 86% observed at the site visits. Common mechanisms of injuries were collisions with objects (33%), falls in icy conditions (28%), and going off jumps (16%). Most serious injuries occurred with contact with motor vehicles. There was no relationship between the type of sled used and the likelihood of injury. CONCLUSIONS: Sledding hills which have obstacles, icy conditions, jumps, or proximity to roads may result in more childhood injuries. Children with no adult supervision are likely at higher risk of injury.

Adolescent↗
PubMed1999

Establishment of primary vestibular schwannoma cultures from neurofibromatosis type-2 patients.

Primary cultures were established from vestibular schwannomas of NF2 patients. The cultured tumor cells were selectively amplified by growth factor supplemented medium and characterized by immunocytochemistry. NF2 cDNA was amplified by RT-PCR and mutations were detected by both the non-isotopic RNase cleavage assay and direct DNA sequencing, no detectable wild-type NF2 transcript was found in cDNA from the cultured cells. Distinguishable morphology and growth rate differences have been observed in different passages of the primary cells. The data suggest that a pure schwannoma primary culture can be established and could be very useful in vitro model for further understanding the NF2 gene function in Schwann cells.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1999

Cancer screening practices among primary care physicians serving Chinese Americans in San Francisco.

Previous research has reported a lack of regular cancer screening among Chinese Americans. The overall objectives of this study were to use a mail survey of primary care physicians who served Chinese Americans in San Francisco to investigate: a) the attitudes, beliefs, and practices regarding breast, cervical, and colon cancer screening and b) factors influencing the use of these cancer screening tests. The sampling frame for our mail survey consisted of: a) primary care physicians affiliated with the Chinese Community Health Plan and b) primary care physicians with a Chinese surname listed in the Yellow Pages of the 1995 San Francisco Telephone Directory. A 5-minute, self-administered questionnaire was developed and mailed to 80 physicians, and 51 primary care physicians completed the survey. A majority reported performing regular clinical breast examinations (84%) and teaching their patients to do self-breast examinations (84%). However, the rate of performing Pap smears was only 61% and the rate of ordering annual mammograms for patients aged 50 and older was 63%. The rates of ordering annual fecal occult blood testing and sigmoidoscopy at regular intervals of three to five years among patients aged 50 and older were 69% and 20%, respectively. Barriers (patient-specific, provider-specific, and practice logistics) to using cancer screening tests were identified. The data presented in this study provide a basis for developing interventions to increase performance of regular cancer screening among primary care physicians serving Chinese Americans. Cancer screening rates may be improved by targeting the barriers to screening identified among these physicians. Strategies to help physicians overcome these barriers are discussed.

Asian↗
PubMed1999

Sequence analysis of the Gluconobacter oxydans RecA protein and construction of a recA-deficient mutant.

The deduced amino acid sequence of Gluconobacter oxydans RecA protein shows 75.2, 69.4, and 66.2% homology with those from Aquaspirillum magnetotacticum, Escherichia coli, and Pseudomonas aeruginosa, respectively. The amino acid residues essential for function of the recombinase, protease, and ATPase in E. coli recA protein are conserved in G. oxydans. Of 24 amino acid residues believed to be the ATP binding domain of E. coli RecA, 17 are found to be identical in G. oxydans RecA. Interestingly, nucleotide sequence alignment between the SOS box of G. orphans recA gene and those from different microorganisms revealed that all the DNA sequences examined have dyad symmetry that can form a stem-loop structure. A G. oxydans recA-deficient mutant (LCC96) was created by allelic exchange using the cloned recA gene that had been insertionally inactivated by a kanamycin-resistance cassette. Such replacement of the wild-type recA with a kanamycin resistance gene in the chromosome was further verified by Southern hybridization. Phenotypically, the recA-deficient mutant is significantly more sensitive to UV irradiation than the wild-type strain, suggesting that the recA gene of G. oxydans ATCC9324 plays a role in repairing DNA damage caused by UV irradiation. Moreover, the mutant strain is much more plasmid transformable than its parent strain, illustrating that G. oxydans LCC96 could be used as a host to take up the recombinant plasmid for gene manipulation.

Acetobacteraceae↗
PubMed1998

A genetic and viral load analysis of the simian immunodeficiency virus during the acute phase in macaques inoculated by the vaginal route.

A comparative genetic analysis of SIV-infected female macaques during the first 120 days postinfection was undertaken. The same dose of a macaque-passaged SIVmac239(nef open) was administered to three macaques intravenously (i.v.) and to three macaques intravaginally (i.VAG). Clinical outcomes observed ranged from rapid to nonprogression, while two of the i.v.-infected macaques developed an uncommon hindleg paresis. Analysis of viral load (bDNA assay) determined that both i.v.- and i.VAG-infected macaques had comparable high viral loads at the observed viral peak of 14 days postinfection. A study of viral quasispecies diversity by the heteroduplex mobility assay indicated that (1) the i.v.-infected macaques had a highly heterogeneous quasispecies population similar to the infecting viral stock; and (2) in two of three i.VAG-infected macaques multiple viral genotypes (minimum, three or four) were observed in blood and lymph tissues at early times postinfection, which indicated that limited numbers of viral variants crossed the vaginal mucosa and established infection. Therefore, the route of infection can clearly influence early viral selection and diversity. In addition, a third i.VAG-infected macaque, which was a rapid progressor, did not seroconvert and progressed to AIDS in 120 days. This macaque exhibited a high viral load and heterogeneous quasispecies. These data demonstrate differences in the quasispecies complexity associated with route of infection and rate of disease progression.

Amino Acid Sequence↗
PubMed1998

Epstein-Barr virus and Hodgkin's disease: further evidence for the three disease hypothesis.

The epidemiology of Hodgkin's disease suggests that it is a heterogeneous condition comprising more than one disease entity. The Epstein-Barr virus (EBV) is present in the Reed-Sternberg cells of a proportion of cases and is likely to play a role in the pathogenesis of these cases. In this study we show that EBV association rates vary with age at diagnosis. We suggest that Hodgkin's disease can be divided into three disease entities on the basis of EBV association and age, thereby providing biological support for the multiple aetiology hypothesis proposed by MacMahon (Cancer Res 1966; 26: 1189-1290).

Adolescent↗
PubMed1998

SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain.

The SH2 domain-containing SHP-1 tyrosine phosphatase has been shown to negatively regulate a broad spectrum of growth factor- and cytokine-driven mitogenic signaling pathways. Included among these is the cascade of intracellular events evoked by stem cell factor binding to c-Kit, a tyrosine kinase receptor which associates with and is dephosphorylated by SHP-1. Using a series of glutathione S-transferase (GST) fusion proteins containing either tyrosine-phosphorylated segments of the c-Kit cytosolic region or the SH2 domains of SHP-1, we have shown that SHP-1 interacts with c-Kit by binding selectively to the phosphorylated c-Kit juxtamembrane region and that the association of c-Kit with the larger of the two SHP-1 isoforms may be mediated through either the N-terminal or C-terminal SHP-1 SH2 domain. The results of binding assays with mutagenized GST-Kit juxtamembrane fusion proteins and competitive inhibition assays with phosphopeptides encompassing each c-Kit juxtamembrane region identified the tyrosine residue at position 569 as the major site for binding of SHP-1 to c-Kit and suggested that tyrosine 567 contributes to, but is not required for, this interaction. By analysis of Ba/F3 cells retrovirally transduced to express c-Kit receptors, phenylalanine substitution of c-Kit tyrosine residue 569 was shown to be associated with disruption of c-Kit-SHP-1 binding and induction of hyperproliferative responses to stem cell factor. Although phenylalanine substitution of c-Kit tyrosine residue 567 in the Ba/F3-c-Kit cells did not alter SHP-1 binding to c-Kit, the capacity of a second c-Kit-binding tyrosine phosphatase, SHP-2, to associate with c-Kit was markedly reduced, and the cells again showed hyperproliferative responses to stem cell factor. These data therefore identify SHP-1 binding to tyrosine 569 on c-Kit as an interaction pivotal to SHP-1 inhibitory effects on c-Kit signaling, but they indicate as well that cytosolic protein tyrosine phosphatases other than SHP-1 may also negatively regulate the coupling of c-Kit engagement to proliferation.

Cell Membrane↗