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Biomedical subjects

R B Jones

Publications and source records attributed to R B Jones.

At least 19 recordsLinked to original sources
PubMed2000

Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4.

Heparan sulfate-regulated transmembrane tyrosine kinase receptor FGFR4 is the major FGFR isotype in mature hepatocytes. Fibroblast growth factor has been implicated in the definition of liver from foregut endoderm where FGFR4 is expressed and stimulation of hepatocyte DNA synthesis in vitro. Here we show that livers of mice lacking FGFR4 exhibited normal morphology and regenerated normally in response to partial hepatectomy. However, the FGFR4 (-/-) mice exhibited depleted gallbladders, an elevated bile acid pool and elevated excretion of bile acids. Cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase, the limiting enzyme for bile acid synthesis, was elevated, unresponsive to dietary cholesterol, but repressed normally by dietary cholate. Expression pattern and cholate-dependent, cholesterol-induced hepatomegaly in the FGFR4 (-/-) mice suggested that activation of receptor interacting protein 140, a co-repressor of feed-forward activator liver X receptor alpha, may mediate the negative regulation of cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase transcription by FGFR4 and cholate. The results demonstrate that transmembrane sensors interface with metabolite-controlled transcription networks and suggest that pericellular matrix-controlled liver FGFR4 in particular may ensure adequate cholesterol for cell structures and signal transduction.

Animals↗
PubMed2000

Cardiac toxicity following high-dose cyclophosphamide, cisplatin, and BCNU (STAMP-I) for breast cancer.

We retrospectively evaluated 443 breast cancer patients treated with high-dose cyclophosphamide, cisplatin, and BCNU (STAMP-I) with autologous stem cell support to characterize the cardiac toxicity of this regimen. Patients had stage II-III (n = 243) or stage IV (n = 200) breast cancer. We observed an overall 5.1% incidence of cardiac complications, both clinical and subclinical, in the whole group: 4.9% in stage II-III and 5.5% in stage IV patients. Clinical cardiomyopathy (CMP) was observed in 1.6% of stage II-III patients (1 case of fatal grade 5 toxicity and 3 cases of grade 3 CMP) and in 3.5% of patients with stage IV disease (1 case of grade 4 and 6 cases of grade 3). The incidence of cardiac toxicity did not differ significantly between the groups. Prior radiation therapy to the mediastinum or left chest wall (P = .001) and advanced age (P = .01) were independent predictors of an increased risk of the appearance of this complication. No pharmacodynamic correlation was observed between any of the 3 drugs and cardiac toxicity.

Adult↗
PubMed2000

Comparative health systems: international collaborative education using the internet.

Between January and June 1998, postgraduate and undergraduate students from seven centres participated in a discussion of suicide from a public health perspective, using a listserver on the Internet. Most contributions were in English but a few were in Spanish with subsequent translation. Eighteen out of 32 students responding to evaluation, found the module worthwhile and their learning objectives were met. After making a few modifications to procedures resulting from the evaluation, further rounds of discussion were started in October 1998. International discussion groups using listservers on the Internet provide a new and apparently effective method of education.

Education, Medical, Continuing↗
PubMed2000

Congenital anomalies in patients with Duane retraction syndrome and their relatives.

PURPOSE: Although the high incidence of skeletal, neural, and other ocular problems has been identified in previous reports of large cohorts of patients with Duane syndrome, there has not been any documentation of anomalies in close relatives. Patients with Duane syndrome have a greater than 50% incidence of associated abnormalities that include deafness, other ocular anomalies, cranial nerve palsies, and skeletal abnormalities. This study was undertaken to review the experience of our strabismus service with patients who have Duane retraction syndrome (DRS) and to delineate the associated anomalies in them and their first-degree relatives. METHODS: A prospective study of all patients with Duane syndrome who were seen at the strabismus service at Moorfields Eye Hospital has been ongoing for the last 4 years. All patients were assessed for the presence of ophthalmologic features of DRS and then referred to the pediatric service for a physical and neurologic examination. First-degree relatives were also examined, and a family pedigree was generated. RESULTS: We have evaluated 68 patients with DRS, of which 60.2% were female patients. The left eye was involved at a ratio of 4:1 in unilateral cases. The number of bilateral cases was 57.3%. Among the patients with DRS, 46% had first-degree relatives with associated abnormalities. CONCLUSIONS: The high incidence of associated anomalies in patients and first-degree relatives may suggest that a common genetic defect is responsible. This has to be confirmed with molecular genetic studies, which were not performed on these families because of a lack of available resources. However, our findings may indicate that the inheritance of Duane syndrome is much higher than the 10% previously reported, if any congenital abnormality is accepted as DRS associated. Children with Duane syndrome may benefit from a full medical assessment, in view of the frequency of other abnormalities, and so may their siblings.

Abnormalities, Multiple↗
PubMed2000

Chlamydia pneumoniae serology: interlaboratory variation in microimmunofluorescence assay results.

The lack of standardization in chlamydia serology has made interpretation of published data difficult. This study was initiated to determine the extent of interlaboratory variation of microimmunofluorescence (MIF) test results for the serodiagnosis of Chlamydia pneumoniae infections. Identical panels of 22 sera were sent to 14 laboratories in eight countries for the determination of IgG and IgM antibodies by MIF. Although there was extensive variation in the numeric titer values, the overall percentage agreement with the reference standard titers from the University of Washington was 80%. For results by serodiagnostic category, the best agreement was for four-fold rise in IgG titers, while the lowest agreement was for negative or low IgG titers. Agreement for IgM titers was 50%-95%. Four laboratories failed to discern false-positive IgM titers possibly because of the presence of rheumatoid factor. Further studies are underway to determine the source of interlaboratory variation for the MIF test.

Antibodies, Bacterial↗
PubMed2000

Struggling behavior in shackled male and female broiler chickens.

Anecdotal evidence suggests that the struggling behavior of shackled broiler chickens may be positively related to compression of the shank and the probable associated discomfort: birds with large shanks tend to struggle more violently than do those with smaller shanks. Males are generally heavier and have thicker shanks than females. Therefore, we tested the hypothesis that, because the leg gaps of shackles are fixed in size, male broilers would struggle more than females. At 42 d of age, 264 floor-reared broilers were cooped in groups of 12 (six males and six females) and were transported from the university farm to the abattoir. Eighty of these served as test birds (n = 40/sex) and were shackled on a moving processing line with a bird of randomly selected sex on either side. Upon shackling, the latencies to struggle, numbers of struggling bouts, and total time spent struggling were recorded during a 1-min test period. Subsequently, the BW and circumference of the right shank (CRS) of each test bird were measured. Male birds were heavier and had thicker shanks than females (both P < 0.0001); they also struggled sooner (P < 0.01) and longer (P < 0.008). When data from males and females were pooled, CRS was negatively correlated with latency to struggle (r = -0.30; P < 0.006) and positively associated with SB (r = 0.23; P < 0.04) and total time spent struggling (r = 0.23; P < 0.04). However, there were no detectable correlations within sex. Body weight was not significantly correlated with any of the struggling behavior measures. Although other gender-related factors may be influential, an interpretation of our findings based on sex differences in CRS seems the most parsimonious. We conclude that use of shackles of fixed leg-gap size may contribute to increased struggling behavior in male broilers.

Abattoirs↗
PubMed2000

Multicenter evaluation of the AMPLICOR and automated COBAS AMPLICOR CT/NG tests for detection of Chlamydia trachomatis.

The fully automated COBAS AMPLICOR CT/NG and semiautomated AMPLICOR CT/NG tests were evaluated in a multicenter trial for the ability to detect Chlamydia trachomatis infections. Test performance compared to that of culture was evaluated for 2,236 matched endocervical swab and urine specimens obtained from women and for 1,940 matched urethral swab and urine specimens obtained from men. Culture-negative, PCR-positive specimens that tested positive in a direct fluorescent-antibody test or in a confirmatory PCR test for an alternative target sequence were resolved as true positives. The overall prevalences of chlamydia were 2.4% in women and 7.2% in men. The COBAS AMPLICOR and AMPLICOR formats yielded concordant results for 98.1% of the specimens. With the infected patient as the reference standard, the resolved sensitivities of COBAS AMPLICOR were 89.7% for endocervical swab specimens, 89.2% for female urine specimens, 88.6% for male urethral swab specimens, and 90.3% for male urine specimens. When results were analyzed as if only a single test had been performed on a single specimen type, the resolved sensitivity was always higher. The resolved specificities of PCR were 99.4% for endocervical swab specimens, 99.0% for female urine specimens, 98.7% for male urethral swab specimens, and 98.4% for male urine specimens. The internal control revealed that 2.4% of the specimens were inhibitory when initially tested. Nevertheless, valid results were obtained for 98.6% of the specimens because 59.1% of the inhibitory specimens were not inhibitory when a second aliquot was tested. The COBAS AMPLICOR and AMPLICOR CT/NG tests for C. trachomatis exhibited equally high sensitivity and specificity with both urogenital swab and urine specimens and thus are well suited for screening for C. trachomatis infection.

Automation↗
PubMed2000

Evaluation of the predictive value of Her-2/neu overexpression and p53 mutations in high-risk primary breast cancer patients treated with high-dose chemotherapy and autologous stem-cell transplantation.

PURPOSE: To ascertain the predictive value of Her-2/neu overexpression and p53 mutations, assessed by immunohistochemistry, in high-risk primary breast cancer (HRPBC) treated with high-dose chemotherapy (HDCT). PATIENTS AND METHODS: We obtained paraffin-embedded tumor blocks from 146 HRPBC patients previously enrolled at our program onto clinical trials of HDCT for four to nine involved axillary lymph nodes, > or = 10 involved axillary nodes, or inflammatory carcinoma. All patients received the same HDCT regimen, with cyclophosphamide, cisplatin, and carmustine (STAMP-I), followed by autologous stem-cell transplantation. Median follow-up was 42 months (range, 5 to 90 months). The same pathologist, blinded to clinical outcome, reviewed all immunostained slides. RESULTS: Positive results for Her-2/neu and p53 were found in 44.5% and 34% of the patients, respectively. Positivity for Her-2/neu was significantly associated with increased risk of relapse and death. No correlation was found between p53 mutations and relapse-free survival (RFS) or overall survival (OS). Multivariate analyses included Her-2/neu overexpression and the following variables previously identified as independent predictors of outcome in this population: tumor size, nodal ratio (number of involved nodes/number of dissected nodes), and hormone receptor status. All four variables had independent value. CONCLUSION: Her-2/neu overexpression is an independent negative predictor of RFS and OS in HRPBC treated with HDCT. Its inclusion in our previously described predictive model increases the predictive capacity of this model for the low-risk subgroup. In contrast, p53 mutations lack predictive value in this setting.

Adult↗
PubMed2000

Incidence of and risk factors for cataract among diabetes clinic attenders.

The incidence of and risk factors for cataract during a mean (standard deviation (SD)) follow-up period of 5.0 (3.0) (range 0.1-12.4) years were examined among 3606 patients (2001 male and 1605 female) with diabetes mellitus from three outpatient clinics at the University Hospital, Nottingham. Among the 3606 patients free of cataract at initial registration who attended the clinic at least twice in the period 1979-1992, the mean (SD) age was 49.2 (17.8) years with a mean (SD) duration of diabetes of 7.6 (9.8) years at initial registration. The incidence of cataract was 10.4 (95% confidence interval (CI), 9.0, 11.9) per 1000 person-years based on 18089 person-years of follow-up. The incidence for females (13.6 (95% CI, 11.0, 16.1)) was greater than in males (8 (95% CI, 6.3, 9. 7)) (P<0.001). The incidence of cataract in insulin-dependent diabetes mellitus (IDDM), non-insulin-treated and insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) were 7.1 (95% CI, 5. 4, 8.9), 11.7 (95% CI, 9.1, 14.3) and 17.8 (95% CI, 12.9, 22.7) per 1000 person-years, respectively. Age-adjustment substantially changed the ordering of risk associated with different types of diabetes. Using a Cox's Proportional Hazards Model for IDDM and NIDDM (insulin and non-insulin-treated) diabetes separately, age and any retinopathy were significant independent predictors of cataract for all groups. Poor metabolic control also was a significant independent predictor of cataract for the IDDM and insulin-treated NIDDM diabetes groups. Duration of diabetes was a significant independent predictor of cataract for the IDDM group. Age at diagnosis of diabetes, systolic and diastolic blood pressure, body mass index, proteinuria, cigarette smoking and creatinine had no significant independent association with cataract when other covariates were considered. These findings will help the identification of those diabetic patients at particular risk of cataract so that clinic time for screening of eyes can be appropriately focused and health care planning for people with diabetes considered.

Adult↗
PubMed1999

Timidity in Japanese quail: effects of vitamin C and divergent selection for adrenocortical response.

Male Japanese quail chicks of two genetic lines selected for low (LS) or high (HS) adrenocortical responses to mechanical restraint were housed in mixed-line groups of 24 in four compartments of a multitier brooder battery at 20 days of age. Quail in two of the four compartments were given vitamin C (ascorbyl-2-polyphosphate, APP, 1 g L-ascorbic acid/L) solution for 48 h, whereas the other birds received untreated tap water as usual before they were tested at 23 days of age. At test, each quail was placed individually in a dark, sheltered compartment of an emergence box and allowed 1 min to acclimatise before a door was raised allowing access to an illuminated and exposed area. Vocalisation and the latencies to head and full emergence were then recorded to measure its fear levels. More LS quail vocalised than did HS ones. They also emerged more rapidly from the sheltered compartment into the illuminated one than HS birds. These findings further support our hypothesis that decreased fearfulness has accompanied genetic selection for reduced adrenocortical responsiveness. Treatment with APP reduced the latency to emerge fully into the exposed compartment, and there were no line x treatment interactions. These results suggest that vitamin C supplementation alleviated fearfulness, regardless of existing line differences in this behavioural trait.

Adrenal Cortex↗
PubMed1999

Incidence of tumor-cell contamination in leukapheresis products of breast cancer patients mobilized with stem cell factor and granulocyte colony-stimulating factor (G-CSF) or with G-CSF alone.

We have assessed tumor contamination of peripheral blood progenitor cells (PBPC) in 203 high-risk breast cancer patients who were prospectively randomized to mobilization with stem cell factor (SCF) plus granulocyte colony-stimulating factor (G-CSF) versus G-CSF alone. The patients then received high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with PBPC support. One bone marrow aspirate obtained before treatment, one whole blood specimen obtained before cytokine infusion, and one to five leukapheresis products were tested for the presence of tumor cells by an alkaline phosphatase immunocytochemical technique with a targeted sensitivity of 1.7 tumor cells per 10(6) hematopoietic cells. Tumor cells were detected in the bone marrow, peripheral blood, and/or PBPC of 21 patients (10%). In 14 patients, bone marrow specimens were tumor-positive; in seven patients, premobilization whole blood specimens were tumor-positive, and in eight patients, leukapheresis products were tumor-positive. In five patients, repetitive or multiple specimens were tumor-positive, and in three cases, marrow, peripheral blood, and PBPC products were all tumor-positive. Nine of the patients in whom tumor cells were found in marrow or peripheral blood were clinical stage II to III and 12 were clinical stage IV. Nine of the tumor-positive patients were in the SCF + G-CSF arm and 12 were in the G-CSF arm. Tumor cells were detected in leukapheresis products of eight patients: three in the G-CSF + SCF arm and five in the G-CSF arm. We conclude that detectable tumor-cell contamination of bone marrow, peripheral blood, and/or PBPC occurred in approximately 10% of patients in this trial and was observed in stage II to III patients, as well as in stage IV patients. No significant difference could be found in the rate of PBPC tumor-cell contamination between patients who received SCF + G-CSF compared with those who received G-CSF alone. Neither mobilization regimen was found to increase the rate of tumor-cell contamination when control premobilization blood samples were compared with leukapheresis products.

Breast Neoplasms↗
PubMed1999

The effect of an insulin releasing agent, BTS 67582, on advanced glycation end product formation in vitro.

BTS 67582 (1,1-dimethyl-2-(2-morpholinophenyl) guanidine fumarate) is an insulin-releasing agent currently in phase II clinical trials. Its effect on advanced glycation end product (AGE) formation was measured in the BSA/D-glucose and L-lysine/glucose-6-phosphate assay systems and Amadori product formation was measured in the BSA/D-glucose assay system, following a 3 week incubation period. In the BSA/D-glucose assay system, 200 mM BTS 67582 caused an approximate 70% inhibition in AGE formation (p<0.001), whilst at 20 mM and 2 mM it caused a marginal inhibition (21%, (p<0.001) and 8% respectively). 200 mM and 20 mM aminoguanidine-HCl inhibited AGE formation by 95% and 69% (p<0.001), respectively, whereas 2 mM aminoguanidine-HCl had no significant effect. Tolbutamide (200 microM) and glibenclamide (100 microM) had significant, but only marginal, effects on AGE formation (16% and 17%, respectively, p<0.01). In the BSA/D-glucose assay system 200 mM BTS 67582 and 200 mM aminoguanidine-HCl retarded Amadori product formation by 88% (p<0.001) and 60% (p<0.01), respectively. BTS 67582 at 20 mM and 2 mM was shown to inhibit Amadori product formation by 67% and 57%, respectively, (p<0.01). In the lysine and glucose-6-phosphate assay system 200 mM BTS 67582 and 200 mM aminoguanidine-HCl were shown to inhibit AGE formation by about 70% and 96% (p<0.001), respectively. Tolbutamide (200 microM) and glibenclamide (100 microM) had no significant effect on AGE formation.

Ferrous Compounds↗
PubMed1999

Latency to traverse a T-maze at 2 days of age and later adrenocortical responses to an acute stressor in domestic chicks.

Latencies to escape from a T-maze, and thereby reinstate visual contact with conspecifics, were measured in broiler chicks at 2 days of age. Chicks were assigned to high- (HP) or low- (LP) performance categories if their escape latencies fell below 25 s or above 75 s, respectively. These chicks were then housed socially in 10 same-category groups (5 HP, 5 LP), each comprising eight birds. At 15 days of age, one chick was taken from each of two randomly selected cages (1 HP, 1 LP) and immediately bled (undisturbed controls). At the same time, another chick was taken from each of these boxes and immersed up to its neck in warm water (partial water immersion, PWI) for 15 min before blood was collected. All chicks were sexed after bleeding. There were no differences between the plasma corticosterone (CS) levels of undisturbed (control) HP and LP chicks. Exposure to PWI significantly increased circulating CS levels, and this elevation was more pronounced in LP than in HP chicks. Male chicks also showed higher stress-induced adrenocortical responses than did females. The present findings suggest that the T-maze responses of young chicks might predict their later adrenocortical responses to a known stressor. This relationship is discussed in terms of individual differences in fearfulness, ability to cope with challenge, and/or stress susceptibility.

Analysis of Variance↗
PubMed1999

Control strategies for aeroallergens in an animal facility.

BACKGROUND: Prevalence of the occupational disease laboratory animal allergy could be reduced if aeroallergen reduction strategies are identified. OBJECTIVE: To reduce worker exposure to Mus m 1, an allergen from laboratory mice, the effect of filter cage tops, increased room ventilation, negatively pressurized ventilated cages, and ventilated cage-changing tables were evaluated. METHODS: Aeroallergen was collected in the ambient air and in the breathing zone and quantified by using a competitive immunoassay. RESULTS: When mice were housed in unventilated cages, ambient allergen was reduced from 5.1 ng/m3 with no cage top to 1.3 ng/m3 with a simple filter-sheet top and 0.8 ng/m3 with a fitted filter-bonnet top (P <. 05). Room ventilation was increased from 6 to 10, 15, and 20 air changes per hour and had little effect on aeroallergen levels and no impact on airborne particulate matter. When mice were housed in ventilated cages, ambient allergen was significantly reduced from 1. 1 ng/m3 at positive cage pressure to 0.3 ng/m3 at negative cage pressure (P <.05). Negative cage pressure combined with handling animals under a ventilated table reduced breathing zone allergen from 28 ng/m3 with neither control strategy in place to 9 ng/m3 (P <. 05). Use of a ventilated table controlled bacterial contamination, measured as colony forming units, found in negatively pressurized cages. CONCLUSION: Three aeroallergen control strategies are use of filter cage tops, operation of negatively pressurized cages, and use of ventilated changing tables.

Air Pollution↗
PubMed1999

Post-mortem incidental finding of cytomegalovirus oophoritis after an allogeneic stem cell transplant.

Cytomegalovirus (CMV) disease is a common and serious complication of allogeneic stem cell transplantation (SCT). Its two most frequent manifestations are interstitial pneumonitis and gastroenteritis. We describe here the first reported case of CMV ovarian infection in an allo-SCT recipient. This patient was included in a clinical trial of high-dose chemotherapy (HDCT) with HLA-matched peripheral SCT for metastatic breast cancer. She expired 53 days after transplantation from organ failure unrelated to her CMV oophoritis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Modification of the pharmacokinetics of high-dose cyclophosphamide and cisplatin by antiemetics.

Interpatient variability in exposure to certain chemotherapy agents can influence patient outcome, particularly with high-dose chemotherapy. We evaluated the possibility of a pharmacokinetic (PK) drug-drug interaction between the antiemetic agents and high-dose cyclophosphamide, cisplatin and BCNU (CPA/cDDP/BCNU). Twenty-three self-selected patients treated with high-dose CPA/cDDP/BCNU followed by autologous hematopoietic progenitor cell support (AHPCS) received ondansetron, lorazepam and diphenhydramine as antiemetics. PK parameters for each chemotherapeutic drug in the regimen were compared with those of 129 patients who received exactly the same chemotherapy but an antiemetic regimen substituting prochlorperazine for ondansetron. In addition, we performed a review of the English literature for reported drug-drug interactions between antiemetics and chemotherapy agents that led to modifications in any PK parameters of the chemotherapy agent. Our retrospective study showed that the mean area under the curve (AUC) for both cyclophosphamide (76,600 vs 90,600 microg/ml/min, P=0.001) and cisplatin (525 vs 648 microg/ml/min, P = 0.01) were significantly lower in the ondansetron group when compared with the prochlorperazine group. The AUC for BCNU was not significantly different in both groups (544 vs 677, P = 0.43). We found only one report of modifications of the PK parameters of high-dose chemotherapy agents due to drug-drug interactions with the most commonly used antiemetics in a review of the English literature between 1966 and 1995. We concluded that the AUC of high-dose cyclophosphamide and cisplatin are significantly lower when ondansetron, as opposed to prochlorperazine, is used as the antiemetic. The small sample size and heterogeneity of this group of patients precludes any outcome analysis of pharmacodynamic endpoints such as toxicity or antitumor effect. Nevertheless, the potential for interactions between antiemetics and chemotherapy agents should be taken into account when using different high-dose chemotherapy regimens.

Adult↗