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Biomedical subjects

D Bowman

Publications and source records attributed to D Bowman.

At least 37 records · Page 2Linked to original sources
PubMed1995

A full likelihood procedure for analysing exchangeable binary data.

A full-likelihood procedure is proposed for analyzing correlated binary data under the assumption of exchangeability. The binomial and beta-binomial models are shown to occur as special cases correspondingly, respectively, to the choice of degenerate and beta-mixing distributions. For a finite exchangeable binary sequence of random variables, expressions for the joint distribution, moments, and correlations of all orders are derived. Maximum likelihood estimates of the moments of all orders are computed and used to estimate correlations and the distribution of the number of responses in a cluster. In an application to developmental toxicology data analysis, the procedure introduced is compared with a beta-binomial and a generalized estimating equation procedure in which mean response and intralitter correlation are linked to dose.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1995

Estimating variance functions in developmental toxicity studies.

The presence of intralitter correlation is a well known issue for analysis of the developmental toxicology data. The intralitter correlation coefficients observed in developmental toxicology data are generally different across dose groups. In this paper we use a generalized estimating equation procedure to model jointly the mean parameters and the intralitter correlation coefficients as functions of dose levels. Our procedure is similar to that used by Prentice and Zhao (1991, Biometrics 47, 825-839) for estimating the mean and variance parameters.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1994

Omega-conotoxin MVIIC reversibly inhibits a human N-type calcium channel and calcium influx into chick synaptosomes.

We have investigated the effects of omega-CmTX MVIIC on the recombinant alpha 1B-mediated calcium channel expressed in HEK 293 cells and on the predominantly N-type calcium channel in chick synaptosomes. omega-CmTX MVIIC potently and reversibly inhibited the calcium current through alpha 1B-mediated calcium channels and inhibited KCl-evoked increases in [Ca2+]i in chick synaptosomes in a concentration-dependent manner.

Action Potentials↗
PubMed1994

Growth of tumor derived activated T-cells for the treatment of cancer.

This report describes the production of Tumor Derived Activated Cell cultures (TDAC, also called tumor infiltrating lymphocytes) from patient tumor biopsies and our preliminary experience growing these cells to therapeutic levels using artificial capillary bioreactor cultures. TDAC were successfully grown in medium containing Interleukin 2 from 80% of the 113 tumor biopsies tested. There was no significant difference in success (growth to 1 x 10(9) cells) comparing primary and metastatic tumors. Many of the tumors were shipped to the laboratory from distant sites. Success rate did decrease with the length of time for tumor transport. Interleukin 4 was beneficial in the development of 1 of 4 TDAC cultures which did not grow with IL-2 only. Seventy-seven bioreactor cultures were initiated for 31 patients. On the average, 1.9 x 10(9) TDAC were inoculated per bioreactor; 3.3 x 10(10) were harvested in 22 days. Twelve liters of medium were required per 1 x 10(10) TDAC produced. TDAC cultures contained T cells with variable ratios of CD4 to CD8 cells. Secreted granulocyte monocyte colony stimulating factor, interferon gamma and tumor necrosis factor were measured in the bioreactor cartridge conditioned medium. Twenty three patients were evaluated. Partial responses were observed in 4 patients including a dramatic remission of scalp nodules in a patient with renal cancer. Results showed that therapeutic amounts of TDAC cells may be produced in a reasonable and cost effective manner using artificial capillary bioreactor cultures.

Biopsy↗
PubMed1993

A three-dimensional view of precursor messenger RNA metabolism within the mammalian nucleus.

A quantitative three-dimensional analysis of nuclear components involved in precursor messenger RNA metabolism was performed with a combination of fluorescence hybridization, immunofluorescence, and digital imaging microscopy. Polyadenylate [poly(A)] RNA-rich transcript domains were discrete, internal nuclear regions that formed a ventrally positioned horizontal array in monolayer cells. A dimmer, sometimes strand-like, poly(A) RNA signal was dispersed throughout the nucleoplasm. Spliceosome assembly factor SC-35 localized within the center of individual domains. These data support a nuclear model in which there is a specific topological arrangement of noncontiguous centers involved in precursor messenger RNA metabolism, from which RNA transport toward the nuclear envelope radiates.

Cell Nucleus↗
PubMed1993

1 alpha,25-Dihydroxyvitamin D3 rapidly increases nuclear calcium levels in rat osteosarcoma cells.

1 alpha,25-Dihydroxyvitamin D3 increases intracellular calcium in rat osteoblast-like cells that possess the classic receptor (ROS 17/2.8) as well as those that lack the classic receptor (ROS 24/1), indicating that a separate signalling system mediates this rapid nongenomic action. To determine the intracellular sites of this calcium increase, cytosolic and nuclear fluorescence (340 nm/380 nm ratio) were measured in Fura 2AM loaded ROS 17/2.8 cells using digital microscopy. Within 5 min, cytosolic fluorescence increased by 29% (P < 0.05) and nuclear fluorescence by 30% (P < 0.01) after exposure to 1 alpha,25-dihydroxyvitamin D3 (20 nM). This effect was blocked by the inactive epimer 1 beta,25-dihydroxyvitamin D3. In an individual cell, cytosolic and nuclear fluorescence increased gradually after 1, 3, and 5 min exposure to vitamin D. Nuclei were then isolated from ROS 17/2.8 cells to directly measure the hormone's effect on nuclear calcium. The calcium content of Fura 2AM loaded nuclei was not affected by increasing the calcium concentration in the incubation buffer from 50 nM to 200 nM. After 5 min, 1 alpha,25-dihydroxyvitamin D3, 20 nM, increased the calcium of isolated nuclei in medium containing 50 nM calcium and 200 nM calcium. 1 beta,25-dihydroxyvitamin D3, 20 nM, had no effect on nuclear calcium but blocked the 1 alpha,25-dihydroxyvitamin D3 induced rise in the isolated nuclei. The results indicate that the nuclear membrane of the ROS 17/2.8 cells contain calcium permeability barriers and transport systems that are sensitive to and specific for 1 alpha,25-dihydroxyvitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pharmacological characterisation of the calcium channels coupled to the plateau phase of KCl-induced intracellular free Ca2+ elevation in chicken and rat synaptosomes.

The effect of various blockers of voltage operated calcium channels (VOCCs) was studied on the non-inactivating, plateau phase of KCl-induced intracellular free Ca2+ ([Ca2+]i) elevation in rat cortical and chicken forebrain synaptosomes. In chicken synaptosomes, omega-CgTx GVIA (0.1 nM to 1 microM) and omega-CgTx MVIIA (0.1 nM to 1 microM), both selective blockers of N-type Ca2+ channels, produced a concentration-dependent inhibition of the plateau phase of [Ca2+]i elevation. omega-CgTx GVIA (IC50 value 28 nM) was more potent than omega-CgTx MVIIA (IC50 value 78 nM), but at submaximal concentrations, took longer to reach its maximum effect (20 min for omega-CgTx GVIA; 10 min for omega-CgTx MVIIA). At 1 microM, the highest concentration tested, each toxin blocked > 85% of [Ca2+]i elevation. The effect of omega-CgTx GVIA on the extent and time-course of inhibition of [Ca2+]i elevation was maintained in a Na(+)-free, choline substituted, medium. omega-Aga IVA (300 nM), a selective blocker of P-type calcium channels, inhibited 28 +/- 5% of [Ca2+]i elevation. The effect of a combination of submaximal inhibitory concentrations of omega-CgTx GVIA (100 nM) and omega-Aga IVA (300 nM) was less than additive. In rat synaptosomes, omega-CgTx GVIA (1 microM) and omega-CgTx MVIIA (1 microM), blocked only 18 +/- 5% and 17 +/- 4% of the plateau phase of free Ca2+ elevation, respectively. omega-Aga IVA produced a concentration-dependent inhibition of [Ca2+]i elevation in this preparation. Threshold inhibition was observed at 1 nM, and maximum inhibition (64 +/- 8%) at 1 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Spontaneous burst firing in cat primary auditory cortex: age and depth dependence and its effect on neural interaction measures.

1. Neural activity was recorded with two independent electrodes separated by 0.5-2 mm, aligned in parallel, and advanced perpendicular to the surface of the cat auditory cortex. Because the experiments were part of a study into laminar interaction the difference in recording depths for the two independently movable electrodes was never > 100 microns. Multi-unit activity on each electrode was separated on-line into single-unit spike-trains with a maximum variance spike sorting algorithm. Off-line controls on the quality of the spike-train separation were routinely performed. The first aim of this study was to describe the age dependence of spontaneous burst firing and to explore if and how it could be explained by age dependent changes in firing rate. The second aim was to investigate a potential layer dependence on burst firing. The third aim was to describe the effect of burst-removal procedures on the shape, strength, and width of the cross-correlogram and to investigate whether an age dependence in burst firing might account for the previously reported age dependence in correlation strengths. 2. Recordings were made from 237 single units from primary auditory cortex in nine adult cats and from 67 units in seven kittens age 10-52 days. The incidence of burst firing as a function of firing rate, age and depth of recording and unit characteristic frequency was investigated. In addition the effect of burst firing on the strength and width of the central peak in 471 neural pair correlograms was analyzed. 3. Burst firing could be distinguished at many different time scales; bursts lasting of the order of 10 s contained bursts with durations of the order of 1 s, which in turn contained bursts of 30-50-ms duration. The analysis in this paper was restricted to the short-duration bursts. 4. Burst firing on the short-time scale of 50 ms was characterized by relatively well defined intervals between the first two spikes (3-15 ms) followed by higher-order intervals with large spread (range 4-50 ms) but with increasing modal interval value. The typical adult five-spike burst template featured spikes at 0, 3.3, 14.6, 27.2, and 34.8 ms. Burst with fewer spikes showed larger intervals between the first three spikes. 5. The probability of occurrence of isolated spikes, pairs, triplets, etc. showed a power-law dependence on firing rate with a coefficient that was significantly lower than expected under Poisson firing conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Variations in bracket placement in the preadjusted orthodontic appliance.

This study was conducted to determine the accuracy of bracket placement with the direct bonded technique. Ten orthodontic faculty members bonded a preadjusted orthodontic appliance on models of five cases of malocclusion in a simulated clinical situation (mannequin). A total of 50 sets of models served as the population of the study. Photographs of the models were measured to determine vertical and angular discrepancies in position between adjacent bracket pairs from a constructed reference line. Variations are evaluated with respect to the classification of malocclusion, specific tooth type, and intra/inter operator differences. A mean of 0.34 mm for the vertical discrepancies and a mean of 5.54 degrees for the angular discrepancies are found in placement of the orthodontic brackets.

Analysis of Variance↗
PubMed1992

The influence of extraction and nonextraction orthodontic treatment on brachyfacial and dolichofacial growth patterns.

The effects of extraction and nonextraction orthodontic treatment mechanics on patients with dolichofacial and brachyfacial growth patterns between one and two standard deviations were studied. Groups underwent treatment of either nonextraction or extraction of four premolars with the appropriate mechanics for the facial type. Changes in the facial axis and correlation between maxillary molar movement and facial axis change were measured. A positive correlation was found between the amount of anteroposterior movement of the upper molar and change in the facial axis in brachyfacial and dolichofacial patients undergoing nonextraction treatment. A weak correlation was found in the extraction treatment groups. No statistically significant difference was found in the facial axis change among any of the groups studied, regardless of facial type or plan of treatment. There were indications of a more severe opening of the facial axis (Ba-Na plane to constructed gnathion) with greater degrees of maxillary molar distal movement in both facial patterns studied.

Adolescent↗
PubMed1991

Establishment and characterization of SV40 T-antigen immortalized human esophageal epithelial cells.

Normal human esophageal autopsy tissue was explanted in serum-free medium. The epithelial outgrowths were subcultured and then transfected by strontium phosphate coprecipitation with plasmid pRSV-T consisting of the RSV-LTR promoter and the sequence encoding the simian virus 40 large T-antigen. The transfected cells, but not the sham-transfected controls, formed multilayered colonies within 3-4 weeks, after which the colonies were transferred and cell strains (HE-451 and HE-457) developed. Both cell strains grew exponentially for 8-10 weeks and then senesced. After a "crisis" of 6-8 months, growth resumed in isolated colonies. One line, HET-1A from HE-457, was developed and has now undergone more than 250 population doublings. This line has retained epithelial morphology, stains positively for cytokeratins and the simian virus 40 T-antigen gene by immunofluorescence, and has remained nontumorigenic in athymic, nude mice for more than 12 months. Karyotypic analysis by Giemsa banding has shown that HET-1A is hypodiploid (34-40 chromosomes). Growth factor studies have shown that HET-1A is stimulated by Ca2+, and inhibited by fetal bovine serum, transforming growth factor-beta 1, and transforming growth factor-beta 2. This serum-free immortalized esophageal cell system will be useful for investigating the action of putative esophageal carcinogens.

Antigens, Polyomavirus Transforming↗
PubMed1991

Effect of phenethyl isothiocyanate on the metabolism of tobacco-specific nitrosamines by cultured rat oral tissue.

The effect of phenethyl isothiocyanate (PEITC) on the metabolism of N'-nitrosonornicotine (NNN) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by cultured rat oral tissue was investigated. Two protocols were used. In one, oral tissue from untreated rats was cultured in the presence of 10 or 50 microM PEITC and either NNN or NNK. The levels of NNN and NNK metabolites released into the culture media were determined by HPLC analysis. The presence of 10 microM PEITC inhibited the formation of all NNN metabolites from 45 to 70% when the concentration of NNN was 1 microM or 10 microM. When the concentration of PEITC was 50 microM the extent of inhibition was from 70 to 90%. alpha-Hydroxylation of NNK was inhibited 70 to 90% and N-oxidation of NNK was inhibited 80 to 90% by 10 microM PEITC. Carbonyl reduction of NNK to NNAL was unaffected by 10 microM PEITC and only slightly inhibited by 50 microM PEITC. In the second protocol, rats were fed NIH-07 diet containing 3 mumol PEITC/g for 1-14 days. The metabolism of NNN by cultured oral tissue from these rats was decreased from 40 to 90% relative to that by tissue from control rats. NNK metabolism was inhibited 40 to 60%. The extent of inhibition was the same when rats were fed PEITC containing diet for 1 or 14 days. NNN and NNK are the only tobacco constituents which induce oral cavity cancer in an animal model. The results of this study suggest the possibility that PEITC may be useful as a chemopreventive agent for oral cavity cancer.

Animals↗
PubMed1991

Iatrogenic transmission of Cytauxzoon felis from a Florida panther (Felix concolor coryi) to a domestic cat.

A laboratory cat died 12 days after intraperitoneal inoculation of a 1 ml suspension containing 1.5 x 10(6) blood mononuclear cells from a Florida panther (Felis concolor coryi). Gross, histologic and ultrastructural investigations revealed the cause of death to be infection by Cytauxzoon felis, a protozoal parasite known to cause a rapidly fatal disease (cytauxzoonosis) in domestic cats. The bobcat (Felis rufus) has been identified as a natural host for C. felis. This report implicates the Florida panther as another possible host for C. felis.

Animals↗
PubMed1990

Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted a randomized clinical trial to determine whether tamoxifen (TAM) plus chemotherapy is more effective than TAM alone in improving disease-free survival (DFS), distant disease-free survival (DDFS), and survival (S) of positive-node, TAM-responsive patients aged greater than or equal to 50 years. Women were randomized among three treatment groups: (1) TAM alone, (2) Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and TAM (ACT), or (3) melphalan (L-PAM), fluorouracil (5-FU), and TAM (PFT). The PFT arm was later modified so that new patients also received Adriamycin (PAFT). Findings from 1,124 eligible patients through 3 years of follow-up indicated a significantly better DFS for ACT-treated patients than for those receiving TAM alone (84% v 67%; P = .0004). An advantage in DDFS and S was also observed after ACT therapy (83% v 73% [P = .04 in the former] and 93% v 85% [P = .04 in the latter]). Both the DFS and DDFS of PAFT-treated patients were better than in those treated by TAM alone (83% v 66%, P = .0002 and 85% v 73%, P = .003). PFT patients also fared better in DFS and DDFS than TAM patients (81% v 72%, P = .07 and 85% v 74%, P = .02). Odds ratios consistently favored the three TAM-plus-chemotherapy groups. No significant S advantage is as yet evident in favor of the PAFT or PFT groups. Of importance is the failure of these studies to demonstrate an unfavorable interaction between the drug regimens used and the TAM, which was administered simultaneously. The findings related to the use of PAFT and PFT are of more biologic than clinical significance since L-PAM is rarely used in the treatment of breast cancer. The major conclusion from this study is the observance of a better outcome in positive-node breast cancer patients aged greater than or equal to 50 years from the use of postoperative prolonged TAM and short-course AC therapy (completed in 63 days) than from prolonged TAM therapy alone.

Aged↗
PubMed1990

Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented protocol B-15 to compare 2 months of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide (AC) with 6 months of conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with breast cancer nonresponsive to tamoxifen (TAM, T). A second aim was to determine whether AC followed in 6 months by intravenous (IV) CMF was more effective than AC without reinduction therapy. Through 3 years of follow-up, findings from 2,194 patients indicate no significant difference in disease-free survival (DFS, P = .5), distant disease-free survival (DDFS, P = .5) or survival (S, P = .8) among the three groups. Since the outcome from AC and CMF was almost identical, the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients. AC seems preferable since, following total mastectomy, AC was completed on day 63 versus day 154 for conventional CMF; patients visited health professionals three times as often for conventional CMF as for AC; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC. The difference in the amount of alopecia between the two treatment groups was less than anticipated. While alopecia was almost universally observed following AC therapy, 71% of the CMF patients also had hair loss and, in 41%, the loss was greater than 50%. This study and NSABP B-16, which evaluates the worth of AC therapy in TAM-responsive patients, indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Systemic therapy in patients with node-negative breast cancer. A commentary based on two National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials.

OBJECTIVE: To determine whether in the previous National Surgical Adjuvant Breast and Bowel Project (NSABP) studies of node-negative breast cancer there were either cohorts of patients with a prognosis favorable enough to preclude using systemic therapy or subsets of patients who failed to benefit from the treatments. DESIGN: Randomized clinical trials with stratification after surgery. SETTING: NSABP trials at institutions in the United States and Canada. PATIENTS: Data were collected on 731 eligible patients (Protocol B-13) with estrogen-receptor-negative tumors who randomly received either no therapy after surgery or sequential methotrexate and fluorouracil (M----F) followed by leucovorin. Data were also collected on 2834 patients (Protocol B-14) with estrogen-receptor-positive tumors who randomly received either placebo or tamoxifen treatment. The percentage of patients surviving disease-free was determined through 4 years of follow-up using life-table estimates. INTERVENTIONS: Protocol B-13 patients received 12 courses of M----F given intravenously on days 1 and 8 every 4 weeks. Leucovorin therapy was begun 24 hours after M----F administration. Protocol B-14 patients received 5-year treatment with either tamoxifen (10 mg twice daily by mouth) or placebo. RESULTS: When the outcome of untreated patients in either trial was related to the stratification variables, women were found to have a disease-free survival of less than 80% through 4 years of follow-up. This percentage is apt to decrease because the probability of treatment failure increases with time. In both trials, all subsets of women benefited from M----F or tamoxifen therapy. CONCLUSIONS: The disease-free survival of all cohorts of node-negative patients with estrogen-receptor-negative or estrogen-receptor-positive tumors was poor enough to justify systemic treatment. The benefits of the therapies used are insufficient to eliminate the need for assessing putatively better regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors.

We evaluated the postoperative use of sequential methotrexate and fluorouracil followed by leucovorin in 679 patients with primary breast cancer, histologically negative axillary nodes, and estrogen-receptor-negative (less than 10 fmol) tumors. No survival advantage was observed with this therapy as compared with no postoperative therapy during four years of follow-up (87 percent vs. 86 percent; P = 0.8). However, there was a significant prolongation of disease-free survival among women who received this therapy as compared with those who did not (80 percent vs. 71 percent; P = 0.003). An advantage was observed in both the patients less than or equal to 49 years old and those greater than or equal to 50. At four years, treatment failure was reduced by 24 percent in the younger group and by 50 percent in the older group. The rates of both local and regional and distant metastases were decreased. These benefits, achieved without the use of an alkylating agent, were associated with tolerable side effects. Multivariate analysis testing for potential interactions failed to identify subgroups of patients who did not benefit from the therapy. These results, although promising, do not obviate the need for additional trials to evaluate potentially better regimens of therapy, but they do suggest that sequential methotrexate-fluorouracil should be used in the control arm in such studies. Their use is also justified for the treatment of patients who refuse to participate in clinical trials, provided the patients meet the eligibility criteria of the present study. Since women with tumors too small for conventional analysis of estrogen-receptor and progesterone-receptor concentrations were not included in this study, we do not recommend systemic treatment for them outside of a clinical trial.

Aged↗