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J Bishop

Publications and source records attributed to J Bishop.

At least 37 records · Page 2Linked to original sources
PubMed2000

Refining the DFNB7-DFNB11 deafness locus using intragenic polymorphisms in a novel gene, TMEM2.

The combined DFNB7-DFNB11 deafness locus maps to chromosome 9q13-q21 between markers D9S1806 and D9S769. We have determined the cDNA sequence and genomic structure of a novel gene, TMEM2, that maps to this interval and is expressed in the cochlea. The mouse orthologue of this gene (Tmem2) maps to the murine dn (deafness) locus on mouse chromosome 19. Screens for transmembrane helices reveal the presence of at least one putative transmembrane domain in the TMEM2 protein. To determine whether mutations in TMEM2 cause hearing loss at the DFNB7-DFNB11 locus, we screened the coding region of this gene in DFNB7-DFNB11 affected families by direct sequencing. All DNA variants that segregated with the deafness and changed the predicted amino acid sequence of TMEM2 were common polymorphisms, as demonstrated by allele-specific amplification of pooled control DNA. Northern blot analysis showed no difference in transcript size or expression level of Tmem2 in dn/dn and control mice. The intragenic polymorphisms in TMEM2 represent a novel centromeric boundary for the DFNB7-DFNB11 interval.

Amino Acid Sequence↗
PubMed2000

Flow cytometric analysis of immunoprecipitates: high-throughput analysis of protein phosphorylation and protein-protein interactions.

BACKGROUND: Activation-induced protein phosphorylation can be studied by Western blotting, but this method is time consuming and depends on the use of radioactive probes for quantitation. We present a novel assay for the assessment of protein phosphorylation based on latex particles and flow cytometry. METHODS: This method employs monoclonal antibodies coupled to latex particles to immobilize protein kinase substrates. Their phosphorylation status is assessed by reactivity with phosphoepitope-specific antibodies. The amount of immobilized protein on the particles was analyzed by direct or indirect immunofluorescence with antibodies to nonphosphorylated epitopes. RESULTS: The assay allowed measurement of phosphorylation of multiple protein kinase substrates in stimulated T cells, including the zeta chain of the T-cell receptor, ZAP-70, CD3, CD5, SHP-1, and ERK-2, using 1-3 microg of total cell protein per sample. The assay provided high resolution of kinetics of phosphorylation and dephosphorylation. Interactions of protein kinase substrates with associated signaling molecules were demonstrated. CONCLUSIONS: The novel assay allows high-throughput quantitative measurement of protein modifications during signal transduction.

Animals↗
PubMed2000

Non-specific antiviral activity of antisense molecules targeted to the E1 region of human papillomavirus.

Antisense phosphorothioate oligonucleotides (ODN1 0x5 OMe) directed against the E1 start region of human papillomavirus 11 (HPV11) can inhibit papillomavirus induced growth of implanted human foreskin in a mouse xenograft model. Administration of a mismatch control oligonucleotide (ODN9 0x5 OMe), in which guanine was replaced with adenine in the same model, had no effect on papilloma induced growth. However, the apparent antiviral activity of ODN1 0x5 OMe was also shown in a lethal mouse cytomegalovirus (CMV) model, in which the oligonucleotides are not expected to have antisense activity. To understand the mechanisms of action of these oligonucleotides, a mismatch oligonucleotide (ODN61 0x5 OMe) was prepared which retained the CpG motifs of ODN1 0x5 OMe. This was tested in the mouse xenograft model and shown to have moderate inhibitory activity. As a definitive experiment, a comparison was made between the efficacy of the active oligonucleotide ODN1 0x5 OMe against two papilloma viruses HPV11 and HPV40. Both these viruses cause benign genital warts, but differ by four bases in their E1 sequence that was the target for ODN1 0x5 OMe. Papillomavirus induced growth in the mouse xenograft model was inhibited by ODN1 0x5 OMe in both cases, suggesting that oligonucleotide molecules have a non-specific antiviral activity that is not directly related to their antisense sequence.

Animals↗
PubMed2000

A phase I trial of docetaxel and gemcitabine in patients with advanced cancer.

BACKGROUND: Docetaxel and gemcitabine are active in a broad range of malignancies. The objective of this phase I trial was to determine the maximally tolerated doses of the combination of docetaxel and gemcitabine. PATIENTS AND METHODS: Patients with advanced cancer, WHO performance status 0-2, who had received up to one prior chemotherapy regimen were treated with gemcitabine on days 1 and 8 and docetaxel on day 8 repeated every 21 days. Prophylactic ciprofloxacin was commenced on day 11 of each cycle and continued until the neutrophil count reached 1.0 x 10(9)/l. G-CSF was not administered. Dose levels studied were docetaxel/gemcitabine: 60/800, 60/1000, 75/1000, 75/1200, 85/1200 and 100/1200 mg/m2. RESULTS: Thirty-nine patients were entered and all were assessable for toxicity. The highest administered dose level was 100 mg/m2 docetaxel and 1200 mg/m2 gemcitabine with dose limiting toxicities of febrile neutropenia, grade 4 neutropenia > or = 7 days, grade 4 thrombocytopenia, grade 3 stomatitis and/or grade 3 fatigue in three out of six patients. Treatment was well tolerated (40 cycles) in the 10 patients treated at the recommended dose level (85/1200) with only a single episode of febrile neutropenia and grade 3 or 4 non-hematologic toxicity was infrequent. There was no significant pulmonary toxicity. Responses were seen in a range of malignancies including non-small-cell lung cancer. CONCLUSIONS: The recommended dose level of 85 mg/m2 docetaxel and 1200 mg/m2 gemcitabine has a favourable toxicity profile and is suitable for further investigation in phase II trials. This non-platinum containing regimen warrants further investigation as a potential alternative to platinum containing regimens in non-small-cell lung cancer and other malignancies.

Adult↗
PubMed2000

Gender roles and geographic location as predictors of emotional distress in Australian women.

This paper examines the emotional distress of women in urban, rural and remote areas of Queensland. A randomised telephone survey of 394 women found that geographical location was not significantly related to perceptions of life quality or distress. Contrary to expectation, urbanisation and isolation were not significant predictors of mental health and factors other than geographical location appear more influential in determining people's emotional wellbeing. One such factor, the gender role that women perceive themselves as fulfilling, was examined in this study and found to be significantly related to emotional distress. Women who saw their role as being submissive, dependent, gentle and timid reported significantly higher rates of distress and women perceiving themselves as bossy, rude and superior reported higher stress, irrespective of where they lived. Scores for the positive gender role of being sensitive, emotional and responsible grew significantly higher as the respondents became more rural/remote. Conversely, scores in the bossy, rude and superior domain were significantly higher in urban areas. This paper discusses the limitations of health research using global urban/rural classification schemes based on size of town or distance from major centres. There is mounting evidence that geographically based classification schemes are essentially minimalist and that more complex grouping variables such as gender role need to be identified.

Adult↗
PubMed2000

Visualization and quantification of breast cancer biomechanical properties with magnetic resonance elastography.

A quasistatic magnetic resonance elastography (MRE) method for the evaluation of breast cancer is proposed. Using a phase contrast, stimulated echo MRI approach, strain imaging in phantoms and volunteers is presented. First-order assessment of tissue biomechanical properties based on inverse strain mapping is outlined and demonstrated. The accuracy of inverse strain imaging is studied through simulations in a two-dimensional model and in an anthropomorphic, three-dimensional finite-element model of the breast. To improve the accuracy of modulus assessment by elastography, inverse methods are discussed as an extension to strain imaging, and simulations quantify MRE in terms of displacement signal/noise required for robust inversion. A direct inversion strategy providing information on tissue modulus and pressure distribution is described along with a novel iterative method utilizing a priori knowledge of tissue geometry. It is shown that through the judicious choice of information from previous contrast-enhanced MRI breast images, MRE data acquisition requirements can be significantly reduced while maintaining robust modulus reconstruction in the presence of strain noise. An experimental apparatus for clinical breast MRE and preliminary images of a normal volunteer are presented.

Breast Neoplasms↗
PubMed2000

Two-dimensional MR elastography with linear inversion reconstruction: methodology and noise analysis.

A methodology for imposing approximate plane strain conditions in magnetic resonance elastography through physical constraint is described. Under plane strain conditions, data acquisition and analysis may be conducted in two dimensions, which reduces imaging and reconstruction time significantly compared with three-dimensional analysis. Simulations and experiments are performed to illustrate the constraint concept. A signal/noise analysis of a two-dimensional linear inversion technique for relative elastic modulus is undertaken, and modifications to the numerical method are described which can reduce the SNR requirements by a factor of two to four. Experimentally measured data are reconstructed to illustrate the performance of the method.

Breast Neoplasms↗
PubMed2000

Influence of chronic barbiturate administration on sleep apnea after hypersomnia presentation: case study.

When sleepiness is excessive, undesirable, inappropriate or unexplained, it often indicates a clinical disorder that is generically termed hypersomnia. One of the leading causes of hypersomnia is sleep apnea. We present the case of a 44-year-old woman with a history of bipolar spectrum disorder and epilepsy who initially showed evidence of hypersomnia. The hypersomnia settled with changes to her medication, but the patient was subsequently found to have severe obstructive sleep apnea. The relation between the patient's medication and sleep apnea is discussed, and the possible respiratory-suppressant effects of chronic barbiturate treatment are considered. The role of other evoking factors within the context of this case and the mechanisms by which drug interactions and psychotropic treatment may worsen, obscure or perpetuate sleep apnea are also examined.

Adult↗
PubMed1999

A randomised phase III study of accelerated or standard fraction radiotherapy with or without concurrent carboplatin in inoperable non-small cell lung cancer: final report of an Australian multi-centre trial.

PURPOSE: To investigate the effects separately and together of (a) shortening overall treatment time and (b) giving concurrent carboplatin in patients having radical radiotherapy for inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between April 1989 and May 1995, 204 patients with medically inoperable or technically unresectable NSCLC localised to the primary site and regional lymph nodes were randomised to receive one of four treatments using a 2 x 2 factorial design: standard radiotherapy, 60 Gy in 30 fractions in 6 weeks (R6); accelerated radiotherapy, 60 Gy in 30 fractions in 3 weeks (R3); standard radiotherapy as in R6 with carboplatin 70 mg/m2/day for 5 days during weeks 1 and 5 of radiotherapy (R6C); accelerated radiotherapy as in R3 with carboplatin 70 mg/m2/day for 5 days during week 1 of radiotherapy (R3C). RESULTS: The estimated median survival of all randomised patients was 15.7 months and estimated 2-year survival was 31%. The longest survival was seen in patients randomised to R6C (median 20.3 months, 41% surviving at 2 years) but there were no statistically significant differences between treatment arms or treatment factors (carboplatin versus no carboplatin, accelerated versus conventional radiotherapy). Haematological toxicity was significantly greater in patients treated with carboplatin and oesophageal toxicity was significantly greater and more protracted in patients treated with accelerated radiotherapy. CONCLUSIONS: This study failed to show a significant survival advantage for any of the treatment arms or factors. Halving overall treatment time resulted in significantly greater oesophageal toxicity with no suggestion of a survival advantage.

Adult↗
PubMed1999

Production of 1alpha,25-dihydroxy-3-epi-vitamin D3 in two rat osteosarcoma cell lines (UMR 106 and ROS 17/2.8): existence of the C-3 epimerization pathway in ROS 17/2.8 cells in which the C-24 oxidation pathway is not expressed.

The secosteroid hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] is metabolized into calcitroic acid through the carbon 24 (C-24) oxidation pathway. It is now well established that the C-24 oxidation pathway plays an important role in the target tissue inactivation of 1alpha,25(OH)2D3. Recently, we reported that 1alpha,25(OH)2D3 is also metabolized into 1alpha,25-dihydroxy-3-epi-vitamin D3 [1alpha,25(OH)2-3-epi-D3] through the carbon 3 (C-3) epimerization pathway in human keratinocytes, human colon carcinoma cells (Caco-2), and bovine parathyroid cells. In a previous study, it was demonstrated that 1alpha,25(OH)2-3-epi-D3 when compared to 1alpha,25(OH)2D3 was less active in stimulating intestinal calcium absorption, calcium mobilization from bone, and induction of calbindin D28k. These findings suggest that the C-3 epimerization pathway, like the C-24 oxidation pathway, may play a role in the target tissue inactivation of 1alpha,25(OH)2D3. In this study, we determined the relationship between the C-24 oxidation and the C-3 epimerization pathways by investigating the metabolism of 1alpha,25(OH)2D3 in two rat osteosarcoma cell lines (UMR 106 and ROS 17/2.8). These two cell lines differ from each other in their ability to metabolize 1alpha,25(OH)2D3 through the C-24 oxidation pathway. It has been previously reported that the C-24 oxidation pathway is expressed only in UMR 106 cells but not in ROS 17/2.8 cells. The results of our present study provide new evidence that both cell lines possess the ability to metabolize 1alpha,25(OH)2D3 into 1alpha,25(OH)2-3-epi-D3 through the C-3 epimerization pathway. Our results also reconfirm the findings of previous studies indicating that UMR 106 cells are the only ones which express the C-24 oxidation pathway out of the two cell lines studied. Furthermore, this study reveals for the first time that the C-3 epimerization pathway may become an alternate metabolic pathway for the target tissue inactivation of 1alpha,25(OH)2D3 in some cells, such as ROS 17/2.8, in which the C-24 oxidation pathway is not expressed.

Animals↗
PubMed1999

Phase I and subsequent phase II study of filgrastim (r-met-HuG-CSF) and dose intensified cyclophosphamide plus epirubicin in patients with non-Hodgkin's lymphoma and advanced solid tumors.

BACKGROUND: To define a maximum tolerated dose (MTD) for the combination of epirubicin and cyclophosphamide with filgrastim (r-met-HuG-CSF) in patients with advanced solid tumors and non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-five patients with advanced solid tumors were enrolled in stages I and II. Twenty-one patients were treated in stage I in sequential cohorts of at least three patients at increasing dosage levels of cyclophosphamide and epirubicin, for up to six cycles every 21 days. At the completion of stage I, a MTD for epirubicin was established. Fourteen patients were treated in stage II, in cohorts of three or more. The epirubicin dose remained constant at the MTD dosage from stage I. Cyclophosphamide was further dose-escalated to establish its MTD. Twenty-one patients with previously untreated non-Hodgkin's lymphoma were treated in stage III with the MTD established in the prior stages. RESULTS: The MTD in stage I was epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with cumulative neutropenia as the dose-limiting toxicity (DLT). Cumulative thrombocytopenia prevented further dose-escalation of cyclophosphamide in stage II. The stage III regimen consisted of six, 21-day cycles of epirubicin 150 mg/m2, cyclophosphamide 1500 mg/m2, vincristine 2 mg, and prednisolone 100 mg for five days with filgrastim support. Nineteen of twenty-one patients (90%) completed six cycles of treatment, eight (38%) without dose reduction. Common toxicity criteria (CTC) grade 4 neutropenia (neutrophil nadir < 0.5 x 10(9)/l) was documented in 85 of 118 cycles (72%). Neutropenic fever was documented in 17 of 21 patients (81%) on at least one occasion. Severe thrombocytopenia (< 25 x 10(9)/l) was seen in fourteen of 118 cycles (12%) and increased with cycle number. There was no significant non-hematological toxicity. CONCLUSION: Significant dose-escalation of epirubicin and cyclophosphamide was possible with filgrastim support. The MTD achieved was approximately double that of standard-dose therapy. This study forms the basis of an ongoing randomized study evaluating dose-intensification in intermediate grade NHL.

Adult↗
PubMed1999

Absence of selection against aneuploid mouse sperm at fertilization.

Is there selection against aneuploid sperm during spermatogenesis and fertilization? To address this question, we used male mice doubly heterozygous for the Robertsonian (Rb) translocations Rb(6. 16)24Lub and Rb(16.17)7Bnr, which produce high levels of sperm aneuploid for chromosome 16, the mouse counterpart of human chromosome 21. The frequencies of aneuploid male gametes before and after fertilization were compared by analyzing approximately 500 meiosis II spermatocytes and approximately 500 first-cleavage zygotes using fluorescence in situ hybridization with a DNA painting probe mixture containing three biotin-labeled probes specific for chromosomes 8, 16, and 17 plus a digoxigenin-labeled probe specific for chromosome Y. Hyperhaploidy for chromosome 16 occurred in 20.0% of spermatocytes and in 21.8% of zygotes. Hypohaploidy for chromosome 16 occurred in 17.0% and 16.7% of spermatocytes and zygotes, respectively. In addition, there was no preferential association between chromosome 16 aneuploidy and either of the sex chromosomes, nor was there an elevation in aneuploidy for chromosomes not involved in the Rb translocations. These findings provide direct evidence that there is no selection against aneuploid sperm during spermiogenesis, fertilization, and the first cell cycle of zygotic development.

Aneuploidy↗
PubMed1999

Effect of caffeine consumption on tissue oxygen levels during hyperbaric oxygen treatment.

Ten men were exposed to hyperbaric oxygen (HBO2), and their tissue oxygen levels were monitored after they drank either placebo or caffeine beverages. Transcutaneous tissue oxygen (PtcO2) monitor measurements in a normobaric air environment were initially obtained from transducers on the subject's chest and foot. The subjects then consumed either the caffeine (3 mg.kg-1) or the placebo beverage, and after 20 min the subjects were pressurized in a hyperbaric chamber to 2.36 atm abs (1 atm = 101.3250 kPa). The test subjects began breathing 100% oxygen at 2.36 atm abs, 30 min after administration of the experimental beverage, and continued for 30 min, after which the final chest and foot PtcO2 measurements were recorded (1 h after ingestion of the test drink). Each subject underwent a second hyperbaric exposure during which the alternate drink was administered (either the placebo or the caffeine), and PtcO2 measurements were again obtained. The increase in right foot PtcO2 values during HBO2 exposure was significantly smaller after caffeine consumption than after placebo (P = 0.0018).

Adult↗
PubMed1999

Near-field speech intelligibility in chemical-biological warfare masks.

It is common knowledge among field personnel that poor speech intelligibility can occur when chemical-biological warfare (CBW) masks are worn: indeed, many users resort to hand signals for person-to-person communicative purposes. This study was conducted in an effort to generate basic information about the problem; its focus was on the assessment of, and comparisons among, the communicative efficiency of seven different CBW units. Near-field word intelligibility was assessed by use of rhyming minimal contrast tests; user and acoustic restrictions were studied by means of diadochokinetic tests and system frequency response. The near-field word intelligibility of six American-designed masks varied somewhat, but overall it was reasonably good; however, a Russian unit did not perform well. Second, three of the U.S. masks were found to produce less physiological restraint than the others, and the Soviet mask produced the greatest physiological restraint. Finally, a few of the CBW masks also exhibited very low levels of acoustic distortion. Accordingly, it was concluded that two of the several configurations studied exhibited superior features. Other factors being equal, they can be recommended for field use and as a basis for the development of future generations of CBW masks. However, it also should be noted that although these devices provided reasonably good speech intelligibility when the listener was close to the talker, they do not appear to do so even at minimal distances.

Adult↗
PubMed1998

Nonviral interferon alpha gene therapy inhibits growth of established tumors by eliciting a systemic immune response.

A plasmid expression system encoding murine IFN-alpha4 and complexed with a protective interactive noncondensing polymeric (PINC) delivery system was used for in vivo immunotherapy treatment of an immunogenic murine renal cell carcinoma, Renca, and a nonimmunogenic mammary adenocarcinoma, TS/A. Mice bearing established tumors were treated with IFN-alpha/polyvinylpyrrolidone (PVP) expression complexes via direct intratumoral injection. Up to 100% inhibition of tumor growth was observed in the treated mice. By using an optimal dose of 96 and 48 microg of formulated IFN-alpha plasmid for the treatment of Renca and TS/A, respectively, 30% (Renca) and 10% (TS/A) of the treated animals remained tumor free. Inhibition of tumor growth was dependent on activation of the immune system. The antitumor activity elicited by IFN-alpha gene therapy was abrogated when mice were selectively depleted of CD8+ T cells. By contrast, depletion of CD4+ T cells resulted in enhanced tumor rejection following IFN-alpha/PVP treatments. Finally, mice that remained tumor free following IFN-alpha gene therapy displayed immune resistance to a subsequent tumor challenge. These data provide evidence that IFN-alpha gene therapy can be used to induce an efficient antitumor response in vivo.

Adenocarcinoma↗
PubMed1998

Trace analysis of SN-38 in human plasma by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method with fluorescence detection was developed and validated for the quantitation of SN-38, the active metabolite of irinotecan (CPT-11), a new anticancer drug. This method uses solid-phase extraction with a C18 column for sample clean-up and concentration following acidification of human plasma with two volumes of 0.1 M HCl. Using blank plasma spiked with SN-38, we found the assay to be linear over the concentration range of 10-500 pM (3.9-195 pg/ml) with acceptable total and within-day imprecision. The recovery of SN-38 ranged from 48.3% (10 pM) to 91.5% (500 pM) whereas that of the internal standard, 20-(S)-camptothecin, was 96.9% (500 pM). This method represents a sizeable increase in sensitivity over other published methods and is shown to be suitable for the measurement of 'trough' concentrations of SN-38 during the treatment of patients with a weekly regimen of irinotecan.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Autism and maternally derived aberrations of chromosome 15q.

Of the chronic mental disabilities of childhood, autism is causally least well understood. The former view that autism was rooted in exposure to humorless and perfectionistic parenting has given way to the notion that genetic influences are dominant underlying factors. Still, identification of specific heritable factors has been slow with causes identified in only a few cases in unselected series. A broad search for genetic and environmental influences that cause or predispose to autism is the major thrust of the South Carolina Autism Project. Among the first 100 cases enrolled in the project, abnormalities of chromosome 15 have emerged as the single most common cause. The four abnormalities identified include deletions and duplications of proximal 15q. Other chromosome aberrations seen in single cases include a balanced 13;16 translocation, a pericentric inversion 12, a deletion of 20p, and a ring 7. Candidate genes involved in the 15q region affected by duplication and deletion include the ubiquitin-protein ligase (UBE3A) gene responsible for Angelman syndrome and genes for three GABA(A) receptor subunits. In all cases, the deletions or duplications occurred on the chromosome inherited from the mother.

Adolescent↗