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Patricia A Johnson

Publications and source records attributed to Patricia A Johnson.

13 recordsLinked to original sources
PubMed2006

Characterization of ovarian surface epithelial cells from the hen: a unique model for ovarian cancer.

To further develop the hen as a model of ovarian adenocarcinoma, we have studied normal and neoplastic ovaries as well as cultured cells from the ovarian surface epithelium (OSE). We characterized the OSE layer of the hen for specific histologic markers and evaluated these markers on tumor tissue. We also isolated and characterized the epithelial cells that are the likely source of the ovarian tumors of the hen. The surface epithelium of normal ovaries demonstrated positive staining for cytokeratin, proliferating cell nuclear antigen (PCNA), progesterone receptor (PR), and negative staining for vimentin. Ovarian tumors demonstrated positive cytokeratin, PCNA, PR, and weak vimentin staining in the gland-like areas. Epithelial cell cultures were obtained by an explant method utilizing small and large yellow follicles. These cells were positive for cytokeratin and negative for vimentin on Days 1 and 3. By Day 10, cytokeratin protein expression was less for some cells, and vimentin expression was weakly present in some cells. Expression of PCNA was observed at Days 1 and 3, but was rarely seen in cells cultured for 10 days. Expression of PR was observed on Day 10 after 24-hr estrogen treatment. Epithelial cells grew slowly in culture, and were susceptible to trypsin or other dissociation treatments.

Adenocarcinoma↗
PubMed2006

Functionality and acceptability of a new electronic insulin injection pen with a memory feature.

OBJECTIVE: The HumaPen Memoir (HPM) is a new reusable insulin injection pen. It possesses an electronic component so that 16 insulin doses are stored in the memory. This study's aim was to evaluate the functionality of the device (i.e., ability to deliver a set dose of insulin), its impact on patient safety, and patient/healthcare professional (HCP) acceptance. RESEARCH DESIGN AND METHODS: In this 6-10-week (3 visit) multinational, multi-centre, open-label, single-arm outpatient study, participants with type 1 or type 2 diabetes were assigned to inject either their prandial or basal insulin dose using the HPM and instructed to record all complaints with the study pen or user manual. Investigators submitted a complaint form to the sponsor for each participant complaint, and for adverse events (AEs) potentially related to the study pen. Where a complaint was possibly related to a pen malfunction, the pen was returned to the sponsor for assessment. Participant/HCP acceptance of the HPM was evaluated using questionnaires. RESULTS: Of the 300 participants (mean age 52 [SD 15] years), 58% were male and 62% had type 2 diabetes. The mean duration of pre-study pen use was 7 years. The average exposure to the HPM was 8.2 (SD 1.6) weeks. Overall, 314 study pens were used (14 were replacements). Functional complaints were reported for 24 devices (7.6%), of which 8 (2.5%) were permanent electronic failures, and 15 (4.8%) were user-related (1 pen not returned for assessment). None of these functional issues resulted in a serious AE. Non-functional complaints were reported for 33 devices (10.5%). There were no pen-related hypoglycemic episodes and 2 pen-related hyperglycemic episodes were reported. The majority of participants (81.4%) preferred the HPM over their pre-study pen. The new insulin pen was generally rated higher than the pre-study pen for pen features and tasks associated with everyday pen use. CONCLUSIONS: No major functional issue of the HPM resulting in a serious AE was reported in this study. Based on the study results this new insulin pen demonstrated a favorable benefit-risk profile.

Adolescent↗
PubMed2005

High progesterone during avian meiosis biases sex ratios toward females.

Evidence of altered primary sex ratios in birds shows that mothers can manipulate the sex of their offspring before oviposition. In birds, females are the heterogametic sex (ZW) and males are homogametic (ZZ). Sex is determined in the first meiotic division, when one sex chromosome is retained in the oocyte and the other segregates to the polar body. Altered primary sex ratios suggest that birds may be capable of biasing the segregation of sex chromosomes during meiosis I. During the time of meiosis I, follicular steroid production is limited primarily to progesterone (P4). We experimentally manipulated the levels of P4 in female domestic chickens during the approximate time of meiosis I. We advanced the ovulation of the first egg of a sequence (or clutch) with a subcutaneous injection of P4. We found a significant effect of P4 dose on the sex of the resulting egg. The high progesterone group produced 25% males whereas the low progesterone group produced 61% males and the control group produced 63% males in the first ovulation of the sequence. We propose that variation in maternal progesterone during the critical time for genetic sex determination is the mechanism for primary sex ratio manipulation in birds.

Animals↗
PubMed2005

Innate IL-10 promotes the induction of Th2 responses with plasmid DNA expressing HIV gp120.

Like most DNA vaccines, intramuscular immunization with plasmid DNA coding for influenza virus haemagglutinin (HApDNA) induced Th1 responses and IgG2a antibodies in mice. However, plasmid DNA coding for HIV gp120 (gp120pDNA) induced Th2-biased responses and predominantly IgG1 antibodies. Responses to gp120pDNA switched to a Th1-type in IL-10-defective mice and to exclusively IgG2a antibodies in IL-4-defective mice. Conversely, antigen-specific IFN-gamma production induced by gp120pDNA or HApDNA was reduced in IL-12-defective mice, whereas addition of plasmid DNA coding for IL-12 enhanced Th1 responses. Plasmid DNA stimulated IL-10 and IL-12 production by macrophages and dendritic cells (DCs) in vitro and anti-IL-10 antibodies enhanced IL-12 production and DC maturation in response to gp120pDNA. Our findings suggest that T cell responses induced by DNA vaccines is influenced by the nature of the antigen, and that the induction of Th2-biased responses with gp120pDNA is mediated in part through the stimulation of innate IL-10, which inhibits activation of DCs that direct the induction of Th1 cells.

Animals↗
PubMed2005

Novel mechanism of immunosuppression by influenza virus haemagglutinin: selective suppression of interleukin 12 p35 transcription in murine bone marrow-derived dendritic cells.

Infection with influenza virus strongly predisposes an individual to bacterial superinfection, which is often the significant cause of morbidity and mortality during influenza epidemics. Little is known about the immunomodulating properties of the virus that lead to this phenomenon, but the effect of the viral components on the development of immune dendritic cells (DCs) may prove vital. In this study, activation of and cytokine secretion by bacterial lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) following treatment with the influenza virus major antigen haemagglutinin (HA) were examined. HA selectively inhibits the release of LPS-induced interleukin 12 (IL12) p70, which is independent of IL10 secretion. Suppression occurs at the transcriptional level, with selective inhibition of p35- and not p40-subunit mRNA expression. The downregulation of IL12 p70 by influenza HA is a novel and unexplored pathway that may be relevant in the predisposition to bacterial superinfection associated with influenza virus infections.

Animals↗
PubMed2004

Messenger RNA and protein expression analysis of betaglycan in the pituitary and ovary of the domestic hen.

Betaglycan was originally characterized as the type III receptor for TGFbeta, yet recent research has indicated that betaglycan can serve as an accessory receptor for inhibin. To understand better the action of inhibin in avian follicular development, we have investigated the expression of betaglycan in the pituitary gland and ovary of the hen. In experiments 1 and 2, betaglycan mRNA was detected at 6 kilobases (kb) by Northern blot analysis (n = 5) in chicken pituitary, granulosa, and theca layers and whole ovary. Expression of betaglycan was greatest in the pituitary gland in experiment 1 and greater in the granulosa layer of small yellow follicles (SYF) compared with the granulosa layer of larger follicles. In experiment 2, betaglycan mRNA was more abundantly expressed in the theca layer compared with the granulosa layer for all follicle sizes, although there was no significant difference in betaglycan expression in the theca layer among follicle sizes. In experiment 3, immunohistochemical analysis revealed betaglycan protein in the anterior pituitary as well as in the ovary (n = 4) and SYF (n = 4). Colocalization studies revealed a high abundance of cells within the anterior pituitary expressing both betaglycan and FSH (n = 4). Betaglycan protein was found in the granulosa layer; however, markedly enhanced staining was observed in the theca layer of ovarian follicles. Our results provide evidence for expression of betaglycan mRNA and protein colocalization with FSH in the anterior pituitary, consistent with known inhibin effects. Ovarian localization of betaglycan, particularly in the theca layer, suggests a paracrine role for inhibin in the hen.

Animals↗
PubMed2004

Ovarian tumor expression of an oviductal protein in the hen: a model for human serous ovarian adenocarcinoma.

OBJECTIVE: We hypothesized that ovarian tumors without oviductal involvement would not express the oviductal protein ovalbumin, the major protein found in the magnum of the hen's oviduct. METHODS: On the basis of gross visual examination, tissues samples were removed from hens determined to have ovarian tumors and were processed, embedded in paraffin, sectioned, mounted on glass slides, and stained with hematoxylin and eosin. Ovarian tumors and other peritoneal lesions were evaluated histologically. Paraffin sections of ovarian and oviductal tissue were deparaffinized and evaluated for the protein expression of ovalbumin, proliferating cell nuclear antigen (PCNA), and progesterone receptor (PR). RESULTS: Hens with ovarian adenocarcinoma without (n = 10) or with (n = 6) oviductal involvement were positive for ovalbumin in the ovary. Ovary sections from normal hens (n = 9) were negative, and oviductal sections from normal hens (n = 3) were positive for ovalbumin. Expression of PCNA protein was abundant in all ovarian tumors (16 of 16). Oviductal epithelial cells strongly expressed PCNA protein. Expression of PR was observed in 9 of 14 ovarian tumors. CONCLUSION: The presence of ovalbumin in ovarian tumors in the absence of any oviductal involvement suggests that ovarian tumors dedifferentiate during the disease process and thereby resemble serous-type ovarian tumors in women.

Adenocarcinoma↗
PubMed2004

Gas-phase databases for quantitative infrared spectroscopy.

The National Institute of Standards and Technology (NIST) and the Pacific Northwest National Laboratory (PNNL) are each creating quantitative databases containing the vapor-phase infrared spectra of pure chemicals. The digital databases have been created with both laboratory and remote-sensing applications in mind. A spectral resolution of approximate, equals 0.1 cm(-1) was selected to avoid degrading sharp spectral features, while also realizing that atmospheric broadening typically limits line widths to 0.1 cm(-1). Calculated positional (wave- number, cm(-1)) uncertainty is </=0.005 cm(-1), while the 1sigma statistical uncertainty in absorbance values is <2% for most compounds. The latter was achieved by measuring multiple (typically >/=9) path length-concentration burdens and fitting a weighted Beer's law plot to each wavenumber channel. The two databases include different classes of compounds and were compared using 12 samples. Though these 12 samples span a range of polarities, absorption strengths, and vapor pressures, the data agree to within experimental uncertainties with only one exception.

Calibration↗
PubMed2003

Therapy after single oral agent failure: adding a second oral agent or an insulin mixture?

AIM: to compare the glycemic response to an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily plus metformin (Mix25+M) with glibenclamide plus metformin (G+M), in patients with type 2 diabetes inadequately controlled with a single oral agent. METHODS: 597 patients treated in a randomized, open-label, 16-week parallel study. Variables evaluated: hemoglobin A1C (A1C), patient symptoms, hypoglycemia rate (episodes/patient/30 days), and incidence (% patients experiencing > or =1 episode). For a subset of patients (N=120), fasting, 1-h, and 2-h postprandial plasma glucose (FPG, 1-h ppPG, 2-h ppPG) in response to a standardized test meal (STM) and self-monitored blood glucose (BG) profiles were measured. RESULTS: improved A1C at endpoint for both groups, and A1C changes from baseline to endpoint were not significantly different between treatments (Mix25+M, -1.87+/-1.35% vs. G+M, -1.98+/-1.28%; p=0.288). Among patients completing STM; endpoint 2-h ppPG was significantly lower with Mix25+M (9.05+/-3.32 mmol/l vs. 12.31+/-3.65 mmol/l; p<0.001), as was 2-h ppPG excursion (2-h ppPGex)(0.38+/-3.23 mmol/l vs. 2.88+/-1.98 mmol/l; p<0.001). Percentage of patients achieving postprandial BG targets (<10 mmol/l) at endpoint was significantly greater with Mix25+M (80% vs. 48%; p<0.001). Although, overall hypoglycemia rates were similar, percentage of patients experiencing and rate of nocturnal hypoglycemia was less with Mix25+M (1% vs. 5%; p<0.01, and 0.01 vs. 0.08 episodes/pt/30 d; p=0.007). Patients reported less polyuria with Mix25+M (p<0.001). CONCLUSION: in patients with type 2 diabetes failing on metformin or a sulfonylurea, Mix25+M provided similar overall glycemic control, lower ppPG, reduced nocturnal hypoglycemia, and fewer hyperglycemic symptoms compared to G+M.

Adult↗
PubMed2003

Comparison of nicotine patch alone versus nicotine nasal spray alone versus a combination for treating smokers: a minimal intervention, randomized multicenter trial in a nonspecialized setting.

This multicenter, randomized, open-label clinical trial was conducted to determine whether the combined use of nicotine patch therapy and a nicotine nasal spray would improve smoking abstinence rates compared to either treatment alone, without behavioral counseling. Data were collected at 15 regional cancer control oncology centers within the North Central Cancer Treatment Group. Of the 1384 smokers randomized to the study, 20% were abstinent from smoking at 6 weeks and 8% were abstinent at 6 months. At 6 weeks, the 7-day point prevalence smoking abstinence rate for the patch alone (21.1%) was superior to the spray (13.6%) but was significantly lower than the rate for combination therapy (27.1%). At 6 months, the 7-day point prevalence abstinence rates were not significantly different among the three groups. Combination nicotine nasal spray and nicotine patches were delivered safely in a nonspecialized outpatient clinical setting and enhanced short-term smoking abstinence rates, but these rates were not sustained at 6 months.

Administration, Cutaneous↗
PubMed2002

Guiding practice improvements in pediatric surgery using multidisciplinary clinical pathways.

Clinical pathways guide the evaluation and care of patient populations and can advance the strategic initiatives of the organization as well. To meet external and internal demands, this organization developed pathways to reduce variability in practice, integrate available evidence into care delivery, improve care coordination and documentation, increase efficiencies, and provide outcomes data to consumers and payers. The authors highlight processes and outcomes of some of the organization's surgical pathways, including guidelines for children with second degree burns grafted with TransCyte, those children hospitalized for tonsillectomy or adenoidectomy, appendectomies, atrial and ventricular septal defects, and percutaneous endoscopic gastrostomy or surgical gastrostomy procedures.

Appendectomy↗
PubMed2002

CPT-11 for bile-duct and gallbladder carcinoma: a phase II North Central Cancer Treatment Group (NCCTG) study.

BACKGROUND: Bile-duct and gallbladder carcinomas are rare cancers. Once they have spread beyond the point of surgical resectability, no therapies have shown meaningful long-term benefit. These cancers are typically refractory to standard chemotherapy agents. Based on preclinical work showing activity of CPT-11, we performed a phase II trial to assess its activity in patients with bile-duct or gallbladder carcinomas. METHODS: Patients with histologic or cytologic evidence of locally advanced or metastatic bile-duct or gallbladder carcinoma were potentially eligible for this study. Patients meeting study eligibility and who signed an informed consent were given CPT-11 125 mg/m2 weekly for 4 wk followed by a 2-wk break from therapy. The starting dose of CPT-11 was later reduced to 100 mg/m2 grade IV toxicity. Patients continued on treatment if they showed evidence of benefit and tolerated therapy. RESULTS: A total of 39 patients were enrolled, and 36 were evaluable. The overall confirmed response rate was 8%. One CR and two PRs were seen. A high frequency of toxicity was seen. However, no unusual or unexpected toxicities occurred. CONCLUSION: CPT-11 is ineffective therapy for patients with locally advanced or metastatic bile-duct or gallbladder carcinoma.

Adult↗