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Biomedical subjects

S Flynn

Publications and source records attributed to S Flynn.

At least 37 records · Page 2Linked to original sources

Including the ultimate: a spiritual focus treatment program in an inpatient psychiatric area of a hospital in partnership with a pastoral counseling center.

Describes how an American Association of Pastoral Counselor (AAPC) accredited pastoral counseling center and a community medical center developed in inpatient psychiatric treatment program which integrated the spiritual/religious resources of patients. Outlines the process of collaboration, some basic principles of the integration of faith resources, the ways that staff resistance surfaced and substantially was overcome, and the positive responses of patients. Notes the decision to base treatment on the religious/spiritual position of patients (rather than of therapists), the role of the therapist in this model, and some relevant isomorphic replications.

Community Mental Health Services↗

Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: a case-control study.

PURPOSE: The purpose of this study is to determine the prognostic significance of overexpression of the HER-2 neu oncoprotein with respect to local relapse following conservative surgery and radiation therapy (CS + RT). METHODS AND MATERIALS: Twenty consecutive patients who sustained a local recurrence as the first and only site of failure following CS + RT comprised the case population base for this study. Only patients who received no adjuvant systemic chemotherapy or tamoxifen were selected for analysis. Following the identification of 20 consecutive local-relapse patients, the patient database was searched for 20 matching control patients who did not sustain a local relapse. Each control patient was matched to the index case with respect to age, menopausal status, follow-up, primary histology, axillary nodal status, and primary tumor size. Both index cases and the matched control group received full course radiation therapy, to a total dose of 64 Gy to the tumor bed. The paraffin-embedded blocks of the original primary tumor of the local-relapse cases and the primary tumor of 20 matched controls were processed for immunohistochemical staining of the HER-2 neu oncoprotein. Each slide was rated on the 3-point scale, 0 representing no stain, 1+ indicating light staining, and 2+ denoted heavy staining (overexpression). RESULTS: Of the 20 index cases, with each of the matched controls, 16 were evaluable for analysis. The 4 cases that were eliminated had inadequate paraffin-embedded material in either the case or the match control for adequate staining. By design of the study, the index case group and control group had similar ages (52 years index vs. 51.4 control), follow-up (10.8 years index vs. 10.5 years control), and histologies. For the immunostaining, a value of 2+ was considered to denote high activity and overexpression, and 0 and 1+ were considered negative values. Using these criteria, a total of 9 of the 16 index cases (56%) exhibited overexpression of HER-2 neu oncoprotein, and only 3 of the 16 control cases (18%) demonstrated high immunoreactivity. The difference in immunostaining between the index and control cases was statistically significant by a Pierson chi-square analysis at the p = 0.03 level. CONCLUSIONS: In this matched case-control study, overexpression of the HER-2 neu oncoprotein appears to have prognostic significance with respect to local relapse in the conservatively treated breast. The correlation of overexpression of HER-2 neu by multivariable analysis with other prognostic factors for local recurrence warrants further investigation. The clinical implications of the study are discussed.

Adult↗

Efficacy of transcutaneous computed tomography--guided fine needle aspiration biopsy in patients with laryngeal squamous cell carcinoma, probable failed radiation therapy, and negative transmucosal biopsies.

For patients with suspected recurrent/persistent laryngeal squamous cell carcinoma (SCC) after external beam radiotherapy (EBRT), routine transmucosal biopsies obtained during direct laryngoscopy may fail to reveal active carcinoma. We evaluated transcutaneous computed tomography-guided fine needle aspiration (CTGFNA) in three consecutive patients who had a persistently fixed true vocal fold after EBRT that had been administered for laryngeal SCC and who had multiple negative transmucosal laryngeal biopsies. All three CTGFNA biopsies were positive, but final pathology confirmed invasive SCC in only one of the three patients. Despite its theoretical advantages, CTGFNA in its present form requires further assessment and/or modification.

Aged↗

Loss of low-density lipoprotein utilization by regressing porcine luteal cells: effects of protein kinase C activation.

We recently reported a decline in low-density lipoprotein (LDL) uptake by regressing porcine luteal cells that correlated with diminished LDL stimulation of progesterone (P) production. The objectives of the present study were to determine 1) whether loss of LDL utilization is a specific lesion in the steroidogenic pathway in regressing luteal cells and 2) whether in vitro activation of protein kinase C (PKC) in mid-cycle luteal cells acutely suppresses LDL utilization. Dispersed cells (4 x 10(4)/0.2 ml) from mid-(Days 6-10, estrus = Day 0; n = 5) or late-(Days 15-18; n = 7) cycle porcine CL were cultured in Dulbecco's Modified Eagle/F-12 medium supplemented with insulin, transferrin, sodium selenite, and aprotinin for 24 h with human (h) LDL (0-100 micrograms/ml), 22(R)-hydroxycholesterol (22[OH]-C;-0-25 micrograms/ml), or pregnenolone (0-1000 nM). P production by mid-cycle luteal cells was dose-dependently increased (p < 0.05) by LDL (up to 2.8-fold), 22(OH)-C (up to 3.2-fold), and pregnenolone (> 3-fold). In contrast, LDL (10-100 micrograms/ml) failed to stimulate P production by late-cycle luteal cells. But 22(OH)-C (up to 4-fold) and pregnenolone (> 10-fold) were as effective in promoting (p < 0.05) steroidogenesis relative to basal levels in late luteal cells as in mid-cycle cultures. The PKC activator, TPA (12-O-tetradecanoyl-phorbol-13-acetate; 10 ng/ml), inhibited (approximately 20%; p < 0.01) basal and LDL-supported steroidogenesis, but did not suppress 22(OH)-C-stimulated P secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibition of cervical carcinoma cell line proliferation by the introduction of a bovine papillomavirus regulatory gene.

Human papillomavirus (HPV) E6 and E7 oncogenes are expressed in the great majority of human cervical carcinomas, whereas the viral E2 regulatory gene is usually disrupted in these cancers. To investigate the roles of the papillomavirus E2 genes in the development and maintenance of cervical carcinoma, the bovine papillomavirus (BPV) E2 gene was acutely introduced into cervical carcinoma cell lines by infection with high-titer stocks of simian virus 40-based recombinant viruses. Expression of the BPV E2 protein in HeLa, C-4I, and MS751 cells results in specific inhibition of the expression of the resident HPV type 18 (HPV18) E6 and E7 genes and in inhibition of cell growth. HeLa cells, in which HPV gene expression is nearly completely abolished, undergo a dramatic and rapid inhibition of proliferation, which appears to be largely a consequence of a block in progression from the G1 to the S phase of the cell cycle. Loss of HPV18 gene expression in HeLa cells is also accompanied by a marked increase in the level of the cellular p53 tumor suppressor protein, apparently as a consequence of abrogation of HPV18 E6-mediated destabilization of p53. The proliferation of HT-3 cells, a human cervical carcinoma cell line devoid of detectable HPV DNA, is also inhibited by E2 expression, whereas two other epithelial cell lines that do not contain HPV DNA are not inhibited. Thus, a number of cervical carcinoma cell lines are remarkably sensitive to growth inhibition by the E2 protein. Although BPV E2-mediated inhibition of HPV18 E6 and E7 expression may contribute to growth inhibition in some of the cervical carcinoma cell lines, the BPV E2 protein also appears to exert a growth-inhibitory effect that is independent of its effects on HPV gene expression.

Bovine papillomavirus 1↗

Prognostic value of DNA flow cytometry in the locally recurrent, conservatively treated breast cancer patient.

PURPOSE: This study attempted to determine the prognostic value of DNA flow cytometry in the treatment of patients with locally recurrent, conservatively treated breast cancer. METHODS AND MATERIALS: Of 433 patients with clinical stage I and II breast cancer treated with conservative surgery and radiotherapy at Yale-New Haven Hospital before January 1985, 50 patients experienced an ipsilateral breast relapse as a first site of treatment failure. Using standard flow-cytometric techniques, DNA ploidy, DNA index, and S-phase fraction (SPF) were measured for 38 of the 50 (76%) paraffin-embedded specimens available for analysis. RESULTS: At a median postrecurrence follow-up of 5.8 years, the 5-year and disease-free survival rates following ipsilateral breast treatment failure were 48% and 54%, respectively. Sixty-three percent of the recurrent tumors were DNA diploid and 37% were aneuploid. Both DNA ploidy and SPF were statistically significant prognostic indicators for 5-year survival and disease-free survival after local recurrence. The 5-year survival rate of the DNA diploid population was 64%, compared with 15% in the aneuploid population (P < .02). Patients with low SPF (< 12%) experienced an 83% 5-year survival rate, compared with a 24% 5-year survival rate in patients with high SPF (> or = 12%) (P < .03). Ploidy and SPF were combined to define the categories of favorable (diploid, low SPF) and unfavorable (diploid, high SPF or any aneuploid subgroups). Patients in the favorable category experienced an 89% 5-year postrecurrence survival rate and a 100% disease-free survival rate, whereas patients in the unfavorable category had a 24% 5-year survival rate and a 32% disease-free survival rate (P < .01). The flow cytometry as a factor correlated with other clinical parameters previously shown to be of prognostic significance in this patient population. In a multivariate analysis, flow cytometry was a statistically significant and independent prognostic factor for disease-free survival following local recurrence. CONCLUSIONS: DNA ploidy and SPF as measured by currently available flow-cytometric techniques show promise as a tool in determining prognosis for the patient with locally recurrent breast cancer. Implications of these findings with respect to issues of adjuvant systemic therapy at the time of local recurrence are discussed.

Adult↗

Pseudorevertants of a lac promoter mutation reveal overlapping nascent promoters.

Four pseudorevertants of a -10 region lacP mutation were isolated. Three of these mutations were found to activate nascent promoters. These mutations were: a -2 G/C----A/T change (-2A) promoting transcription at position +11, a +1 A/T----T/A change (+1T) promoting transcription initiation at position +13, and a +10 C/G----A/T change (+10A) promoting transcription initiation at a complex series of positions. The fourth mutation [a -12 T/A----A/T change (-12A)] promotes transcription initiation at -1. The promoters activated by mutations -12A, -2A and +1T resembled the canonical sigma 70 promoter sequences. The +10A promoter activity is also dependent upon the sigma 70 holoenzyme but can not be readily assigned to a specific promoter sequence.

Escherichia coli↗

Alleles at the PRH1 locus coding for the human salivary-acidic proline-rich proteins Pa, Db, and PIF.

We cloned and sequenced the entire exon and intron structures of Db and Pa genetic determinants at the PRH1 locus. Their derived amino acid sequences and that previously determined for the PIF protein completely explain the electrophoretic phenotypes of the acidic proline-rich proteins (PRPs) Pa, Db, and PIF. Thus, the Cys substitution near Arg 106 in the Pa protein sterically interferes with proteolytic cutting at Arg 106 and accounts for the single-banded phenotype. In contrast, the Db and PIF proteins are proteolytically cut at Arg 106 and show a double-banded phenotype. The Db protein has an extra 21-amino acid repeat that accounts for its larger size compared with the equal sized Pa monomer and PIF proteins. Several amino acid substitutions account for the charge and mobility differences of the Pa, Db, and PIF proteins in isoelectric-focusing gels. These DNA/protein correlations, as well as the extremely similar genomic-DNA sequences that differ by less than 1%, establish that Pa, Db, and PIF are alleles at the PRH1 locus. On the basis of the DNA sequences, we conclude that Db and Pa alleles diverged more recently from a common precursor than did the PIF allele from its precursor.

Alleles↗

Primary osteogenic sarcoma of the bladder. Case report and review of the literature.

Primary osteogenic sarcoma of the bladder is an extremely rare disease. Fewer than 30 cases of tumors of the bladder containing bone or cartilage have been reported. Only 14 cases of well-documented primary osteogenic sarcoma of the bladder appear in the world's literature. The authors describe the first detailed description of such a patient treated with radiotherapy and chemotherapy as well as provide a review of this rare and interesting entity.

Humans↗

Diagnosis of B cell lymphoma by analysis of immunoglobulin gene rearrangements in biopsy specimens obtained by fine needle aspiration.

Histologic diagnosis of lymphoma is far more difficult in the disaggregated cells obtained by percutaneous aspiration of lymph nodes than in tissue sections prepared from excisional biopsy specimens. However, the simplicity, economy, and safety of aspiration biopsy makes this an attractive diagnostic option in certain situations. In the present study, we demonstrate that lymph node aspirates provide material that is both suitable and sufficient for accurately detecting clonal proliferations of B cells by analysis of immunoglobulin gene rearrangements. The rearrangements detected in aspirated tissue serve as clonal markers that can be directly compared with the rearrangements found in histologically confirmed lymphoma removed by open biopsy. The application of gene rearrangements to aspirated material therefore offers a useful method of diagnosing lymphoma, particularly for the purposes of more thorough staging at initial presentation or the evaluation of tissues for possible relapse.

B-Lymphocytes↗

Cerebrospinal fluid anion transport: studies of pertechnetate in unanesthetized sheep.

Perfusion of the ventriculocisternal system in unanesthetized sheep was used to quantify the pathways by which the pertechnetate anion (TcO4-) may leave the cerebrospinal fluid space. The largest fraction (about 89%) was removed from the fluid before it reached the cisterna magna; this extraction was significantly inhibited by iodide ion in the perfusion fluid. One-fifth of the extracted pertechnetate remained in the head of the animal for over 3 hours. Only about 3% of the infused pertechnetate was resorbed with the bulk flow of cerebrospinal fluid through the arachnoid villi. These results are consistent with the concept of a specific brain channel for removal of anions. As pertechnetate and iodide ion are thought to be transported by the same mechanisms, the physiological role of this channel may be maintenance of a very low iodide concentration in the extracellular fluid of the brain.

Animals↗

Comparison of cinoxacin and trimethoprim-sulfamethoxazole in the treatment of urinary tract infections.

Forty women with uncomplicated urinary tract infections owing to susceptible organisms were assigned randomly to 500 mg. cinoxacin or 160--800 mg. trimethoprim-sulfamethoxazole twice daily for 10 days. Of 20 patients receiving cinoxacin none had bacteriuria during or 7 days after therapy, and 2 of 15 (13 per cent) were reinfected within 30 days. Of 20 patients receiving trimethoprim-sulfamethoxazole 1 (5 per cent) had bacteriuria during therapy, 19 were uninfected during and 7 days after therapy, and 3 of 15 (20 per cent) were reinfected within 30 days. Adverse reactions occurred in 2 patients (10 per cent) in each group. Anal and vaginal Enterobacteriaceae maintained their sensitivity to cinoxacin. Three patients (20 per cent) on trimethoprim-sulfamethoxazole presented with and 3 acquired anal Enterobacteriaceae resistant to the drug and 2 (13 per cent) acquired vaginal Enterobacteriaceae that were resistant. Cinoxacin was as effective as trimethoprim-sulfamethoxazole without the emergence of resistant bacteria associated with trimethoprim-sulfamethoxazole.

Adult↗

Myocardial characteristics of thyroxine stimulated hypertrophy. A structural and functional study.

The effects of thyroxine-stimulated hypertrophy (TSH) were studied in the porcine left ventricular myocardium. Hypertrophy was produced in six adult pigs by administration of triiodothyronine (1 mg/kg; i.v.) for eight days. Six pigs served as controls. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 47%. With hypertrophy there was a significant increase in heart rate, blood pressure and myocardial blood flows. Minimal coronary resistance measured during adenosine infusion was lower in the TSH group compared with the control group. Anatomic studies revealed a balanced proliferative response of mitochondria, myofibrils and the t-tubular system during TSH. Analysis of the microvasculature indicated that the capillary and arteriolar beds both experienced growth which paralleled myocyte growth during TSH. These results suggest that thyroxine administration promotes angiogenesis in the microvascular bed which provides a partial anatomic rationale for the lowered minimal coronary resistance.

Animals↗

Innovation in general practice: a service for teenagers.

Offering healthcare services in primary care settings, wherever appropriate, has been the major focus of NHS development this decade (NHSE 1996). In this article, the authors discuss the setting up and running of a collaborative community youth health service, an innovation that targeted a neglected patient group in the community using facilitated workships.

Adolescent↗

Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials.

The enteric flora comprise approximately 95% of the total number of cells in the human body and are capable of eliciting immune responses while also protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract (GIT) may also be implicated in the pathogenesis of several chronic conditions such as inflammatory bowel disease (IBD). The University College Cork-based Probiotic Research Group has successfully isolated and identified lactic acid bacteria (LAB) which exhibit beneficial probiotic traits. These characteristics include the demonstration of bile tolerance; acid resistance; adherence to host epithelial tissue; and in vitro antagonism of potentially-pathogenic micro-organisms or those which have been implicated in promoting inflammation. The primary objective of this report is to describe the strategy adopted for the selection of potentially effective probiotic bacteria. The study further describes the evaluation of two members of the resulting panel of micro-organisms (Lactobacillus salivarius subsp. salivarius UCC118 and Bifidobacterium longum infantis 35624) under in vitro conditions and throughout in vivo murine and human feeding trials. Specifically, an initial feeding study completed in Balb/c mice focused upon (i) effective delivery of the probiotic micro-organisms to the GIT and evaluation of the ability of the introduced strains to survive transit through, and possibly colonise, the murine GIT; (ii) accepting the complexity of the hostile GIT and faecal environments, development of a method of enumerating the introduced bacterial strains using conventional microbiological techniques; and (iii) assessment of the effects of administered bacterial strains on the numbers of specific recoverable indigenous bacteria in the murine GIT and faeces. Additional research, exploiting the availability of murine models of inflammatory bowel disease, demonstrated the beneficial effects of administering probiotic combinations of Lactobacillus salivarius UCC118 and Bifidobacterium longum infantis 35624 in prevention of illness-related weight loss. A further ethically-approved feeding trial, successfully conducted in 80 healthy volunteers, demonstrated that yoghurt can be used as a vehicle for delivery of Lactobacillus salivarius strain UCC118 to the human GIT with considerable efficacy in influencing gut flora and colonisation.

Animals↗