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Biomedical subjects

B Bowen

Publications and source records attributed to B Bowen.

At least 37 records · Page 2Linked to original sources

Three-dimensional microscopy of the Rad51 recombination protein during meiotic prophase.

An open question in meiosis is whether the Rad51 recombination protein functions solely in meiotic recombination or whether it is also involved in the chromosome homology search. To address this question, we have performed three-dimensional high-resolution immunofluorescence microscopy to visualize native Rad51 structures in maize male meiocytes. Maize has two closely related RAD51 genes that are expressed at low levels in differentiated tissues and at higher levels in mitotic and meiotic tissues. Cells and nuclei were specially fixed and embedded in polyacrylamide to maintain both native chromosome structure and the three dimensionality of the specimens. Analysis of Rad51 in maize meiocytes revealed that when chromosomes condense during leptotene, Rad51 is diffuse within the nucleus. Rad51 foci form on the chromosomes at the beginning of zygotene and rise to approximately 500 per nucleus by mid-zygotene when chromosomes are pairing and synapsing. During chromosome pairing, we consistently found two contiguous Rad51 foci on paired chromosomes. These paired foci may identify the sites where DNA sequence homology is being compared. During pachytene, the number of Rad51 foci drops to seven to 22 per nucleus. This higher number corresponds approximately to the number of chiasmata in maize meiosis. These observations are consistent with a role for Rad51 in the homology search phase of chromosome pairing in addition to its known role in meiotic recombination.

Amino Acid Sequence↗

Asymmetric predominantly ipsilateral blepharospasm and contralateral parkinsonism in an elderly patient with a right mesencephalic cyst.

A 66-year-old woman presented with a 3-year history of predominantly right-sided blepharospasm and a 1-year history of progressive predominantly left-sided hemiparkinsonism manifested by a left upper extremity resting tremor and left-sided bradykinesia. Magnetic resonance imaging of the brain revealed a large right mesencephalic cyst with mass effect. Positron emission tomography revealed bilateral striatal hypometabolism consistent with nigrostriatal dopaminergic dysfunction. The association of predominantly ipsilateral blepharospasm and predominantly contralateral hemiparkinsonism is very rare, and its association with a posterior fossa space-occupying lesion has been reported only once. This is the second report of such an association and the first description of adult-onset symptomatology.

Aged↗

Engineering secondary metabolism in maize cells by ectopic expression of transcription factors.

Manipulation of plant natural product biosynthesis through genetic engineering is an attractive but technically challenging goal. Here, we demonstrate that different secondary metabolites can be produced in cultured maize cells by ectopic expression of the appropriate regulatory genes. Cell lines engineered to express the maize transcriptional activators C1 and R accumulate two cyanidin derivatives, which are similar to the predominant anthocyanin found in differentiated plant tissues. In contrast, cell lines that express P accumulate various 3-deoxy flavonoids. Unexpectedly, P-expressing cells in culture also accumulate phenylpropanoids and green fluorescent compounds that are targeted to different subcellular compartments. Two endogenous biosynthetic genes (c2 and a1, encoding chalcone synthase and flavanone/dihydroflavonol reductase, respectively) are independently activated by ectopic expression of either P or C1/R, and there is a dose-response relationship between the transcript level of P and the degree to which c2 or a1 is expressed. Our results support a simple model showing how the gene encoding P may act as a quantitative trait locus controlling insecticidal C-glycosyl flavone level in maize silks, and they suggest how p1 might confer a selective advantage against insect predation in maize.

Journal Article↗

Fluid resuscitation following a burn injury: implications of a mathematical model of microvascular exchange.

A validated mathematical model of microvascular exchange in thermally injured humans has been used to predict the consequences of different forms of resuscitation and potential modes of action of pharmaceuticals on the distribution and transport of fluid and macromolecules in the body. Specially, for 10 and/or 50 per cent burn surface area injuries, predictions are presented for no resuscitation, resuscitation with the Parkland formula (a high fluid and low protein formulation) and resuscitation with the Evans formula (a low fluid and high protein formulation). As expected, Parkland formula resuscitation leads to interstitial accumulation of excess fluid, while use of the Evans formula leads to interstitial accumulation of excessive amounts of proteins. The hypothetical effects of pharmaceuticals on the transport barrier properties of the microvascular barrier and on the highly negative tissue pressure generated postburn in the injured tissue were also investigated. Simulations predict a relatively greater amelioration of the acute postburn edema through modulation of the postburn tissue pressure effects.

Burns↗

Psychiatric symptoms, atypical dementia, and left visual field inattention in corticobasal ganglionic degeneration.

We longitudinally examined the neuropsychological and psychiatric characteristics of an adult male with pathologically confirmed corticobasal ganglionic degeneration (CBGD). The patient was seen on an inpatient and outpatient basis by members of the Departments of Neurology and Radiology of the University of Miami School of Medicine. Longitudinal neuropsychological testing revealed a lateralized cortical-subcortical dementia and left visual field inattention consistent with neurological and postmortem neuropathological findings of greater right hemisphere dysfunction. Symptoms of depression and obsessive-compulsive symptomatology were also documented. Our findings are consistent with prior reports indicating that CBGD is characterized by lateralized cerebral dysfunction and suggest that a detailed neuropsychological examination is a useful procedure to assist in the differential diagnosis of this movement disorder.

Aged↗

Chest position and pulmonary deposition of surfactant in surfactant depleted rabbits.

AIMS: To investigate the correlation between chest position and the distribution of surfactant in the lungs of surfactant depleted rabbits, to corroborate current guidelines on the intratracheal instillation of exogenous surfactant in newborns. METHODS: Twelve tracheotomised rabbits, depleted of pulmonary surfactant by saline bronchoalveolar lavage, were given intratracheal 99m Technetium labelled Exosurf in three positions (prone, right side down, and left side down) (n = 4 in each group). They were monitored for 10 minutes using dynamic gamma scintigraphy monitoring. Instillation completed, the lateral lying animals were turned to the opposite side to determine whether redistribution of the surfactant had taken place. The amount of radiolabelled surfactant deposited at the peripheral, central, dorsal and ventral parts of the lungs was then estimated by gamma counting of the lung sections at necropsy. RESULTS: Both gamma scintigraphy and gamma counting showed similar rates and total amount of surfactant accumulation in both lungs of the prone animals. In the lateral lying animals surfactant accumulated at a significantly faster rate in the dependent lungs: the amount of surfactant deposition was three to 14-fold that in the raised lungs (p = 0.017; nested ANOVA). Changing the chest position immediately after instillation did not redistribute the surfactant. In all three groups of animals there was no significant difference in deposition between the peripheral, central, ventral and dorsal parts of the lungs. CONCLUSIONS: Pulmonary distribution of intratracheally instilled surfactant is largely determined by gravity, and changing the chest position after instillation does not result in any redistribution of the surfactant. During the instillation of exogenous surfactant to newborn infants, keeping the chest in the horizontal position may therefore result in the most even distribution of the surfactant in the two lungs. Further deposition studies are required to evaluate the validity of the current recommendations on surfactant administration.

Animals↗

The practice of risk adjustment.

This article focuses on risk adjustment under health care reform. It examines reasons for risk adjustment, how those reasons affect the method of adjustment, and practical issues that arise in the process of adjusting for risk. The paper concludes that adjusting payments to health plans makes the most sense. It advocates a risk adjustment agency that is regionally based and supportive of the public good. For risk adjustment to work, there must be a well-defined market and barriers to entry and exit.

Actuarial Analysis↗

The myb-homologous P gene controls phlobaphene pigmentation in maize floral organs by directly activating a flavonoid biosynthetic gene subset.

The maize P gene, which specifies red pigmentation of the kernel pericarp, cob, and other floral organs, has been an important model since the early days of modern genetics. Here we show that P encodes a Myb homolog that recognizes the sequence CCT/AACC, in sharp contrast with the C/TAACGG bound by vertebrate Myb proteins. P binds to and activates transcription of the A1 gene required for 3-deoxy flavonoid and phlobaphene biosynthesis, but not the Bz1 gene required for anthocyanin biosynthesis. The maize C1 gene, which also encodes a Myb homolog, activates both the A1 and Bz1 genes, but only in the presence of a basic-helix-loop-helix coactivator encoded by the maize genes R or B. These results indicate that Myb homologs can differentially regulate gene expression by binding different DNA sequences, through combinatorial interactions with other factors, or both.

Animals↗

Pharmacokinetics of a novel retinoid AGN 190168 and its metabolite AGN 190299 after intravenous administration of AGN 190168 to rats.

The pharmacokinetics of AGN 190168, a novel synthetic retinoid, and its major metabolite, AGN 190299, in rat blood after intravenous administration was investigated. Approximately 4.4 mg kg-1 (high dose) or 0.49 mg kg-1 (low dose) of AGN 190168 was administered to rats via the femoral vein. Blood was collected from the femoral artery at various time points during an 8 h period. Blood concentrations of AGN 190168 and AGN 190299 were determined by a specific and sensitive high-pressure liquid chromatographic (HPLC) method. AGN 190168 was rapidly metabolized in rats. The only detectable drug-related species in the blood was AGN 190299. Therefore, only pharmacokinetics of AGN 190299 were calculated. Elimination of AGN 190299 appeared to be non-linear after administration of the high dose, and linear after administration of the low dose. The maximum elimination rate (Vmax) and the concentration at half of the Vmax (km), as estimated by a Michaelis-Menten one-compartment model, were 7.58 +/- 2.42 micrograms min-1 (mean +/- SD) and 6.10 +/- 1.58 micrograms mL-1, respectively. The value of the area under the blood concentration time curve (AUC) was 9.54 +/- 1.68 micrograms h mL-1 after administration of the high dose and 0.594 +/- 0.095 micrograms h mL-1 after administration of the low dose. The clearance value was 7.79 +/- 1.20 mL min-1 kg-1 after the high dose, statistically significantly different from that after the low dose (p < 0.05), 14.0 +/- 2.2 mL min-1 kg-1. The terminal half-life (t1/2) was 1.25 +/- 0.74 h for the high-dose group and 0.95 +/- 0.16 h for the low-dose group. Study results demonstrate rapid systemic metabolism of AGN 190168 to AGN 190299, non-linear pharmacokinetics of AGN 190299 after the 4.4 mg kg-1 dose, and the lack of difference in disposition profiles between sexes after intravenous administration of AGN 190168 to rats.

Animals↗

Imaging in acute basilar artery thrombosis.

The aim of this study was to review the imaging features in acute (< 24 h) basilar artery thrombosis. CT and MR studies in 11 patients with clinical diagnosis of acute basilar artery thrombosis were retrospectively reviewed. MR angiography was obtained in 4 patients. Correlation with clinical symptoms was performed. Multiple cranial nerve palsies and hemiparesis were the most common clinical symptoms at presentation. CT revealed hyperdense basilar arteries (n = 7) and hypodensities in the posterior circulation territory (n = 8). In one instance, the infarction was hemorrhagic. MR imaging showed absence of flow void within the basilar in 6 patients and MRA (using both PC and TOF techniques) confirmed absence of blood flow in 4 basilar arteries. One week after presentation, 5 patients died. Autopsy was obtained in 1 case and confirmed the diagnosis of basilar artery thrombosis. Basilar artery thrombosis has fairly typical imaging features by both CT and MR. MRA may be used to confirm the diagnosis. Prompt recognition may lead to early thrombolytic treatment and may improve survival.

Acute Disease↗

A comparison of six different plating media used in the isolation of Salmonella.

Seventeen Canadian Federal, Provincial and Public Health Laboratories took part in different phases of a comparative/collaborative study that evaluated rapid methods to the standard Health Protection Branch (HPB) method for the detection of Salmonella. A variety of commercial media were tested, including Brilliant Green Sulpha Agar, Bismuth Sulphite Agar, Hektoen Enteric Agar, Xylose Lysine Deoxycholate Agar, EF-18 Agar and Rambach Agar. Each laboratory compared up to six of these different plating media. Plating of 123 salmonellae cultures and 28 artificially-inoculated foods showed the recovery of Salmonella spp. on the six plating media to be within one log. Therefore, quantitative testing of the media showed them to be comparable in the recovery of salmonellae. Qualitative testing of the six media during the comparative/collaborative study of various methods showed that EF-18 Agar recovered the greatest number of isolates. Hektoen Enteric Agar ranked second, with the other agars being comparable in their recovery of Salmonella spp. Problems with the various media are summarized. Based on our results and those of other researchers, it is recommended that Bismuth Sulphite Agar be compulsory and that at least one other agar be used for newly developed cultural procedures.

Bacteriological Techniques↗

A comparison study of the EF-18 agar/Hydrophobic Grid Membrane Filter (HGMF) method and the enzyme linked antibody (ELA)/HGMF method to the HPB standard method in the isolation of Salmonella.

As part of a comparative and collaborative study of rapid methods for the detection of Salmonella and the standard Health Protection Branch (HPB) method, six Federal and Provincial Laboratories compared the EF-18 agar/Hydrophobic Grid Membrane Filters (HGMF) method to the standard HPB method. Two Federal Laboratories also compared the enzyme linked antibody (ELA)/HGMF method (which is a further development of the EF-18 agar/HGMF method) to the standard method. During this study the false-negative rates ranged from 0% to 15% for the standard HPB method, from 5.88% to 43.5% for the EF-18 agar/HGMF method, and from 0% to 10.5% for the ELA/HGMF method. The EF-18 agar/HGMF method did not compare well with the standard HPB method due to the number of false-negatives. Problems with this method resulted from the inability to isolate colonies of Salmonella on the HGMF due to the small colony size, abnormal colony coloration, and overgrowth by competitors. The ELA/HGMF method, however, was shown to be comparable to the standard HPB method. The main advantages of this method are that the antibody-staining step is independent of colony coloration and carbohydrate utilization on the plating media; the ability to detect some unusual strains of Salmonella irrespective of their atypical reactions on the media; and the ELA staining can indicate the presence of Salmonella even when the HGMF is overgrown by competitors. Also, cultural confirmation can proceed simultaneously yet independently of the ELA staining procedure. The data presented here indicate that this method is worth further study.

Bacteriological Techniques↗

Survival and recovery of Aeromonas hydrophila in water: development of methodology for testing bottled water in Canada.

Proposed changes to the Regulations for bottled water in the Food and Drugs Act of Canada include criteria for Aeromonas hydrophila (0 colony-forming units/100 mL water). The development of the methodology used to support these proposed Regulations and the survival of A. hydrophila in inoculated water are described. The methodology used in the isolation of A. hydrophila includes the use of hydrophobic grid membrane filters (HGMF), a resuscitation step on tryptic soy agar, and selective plating on membrane-Aeromonas-trehalose agar and Aeromonas medium. Aeromonas hydrophila proliferated and survived in inoculated water for up to 60 days or longer depending on the other contaminating bacteria. The presence of Pseudomonas aeruginosa enhanced the survival of A. hydrophila and enabled this bacteria to survive for more than 60 days.

Aeromonas hydrophila↗

The survival and recovery of Pseudomonas aeruginosa and its effect upon salmonellae in water: methodology to test bottled water in Canada.

Methodology used to support changes to the Regulations for bottled water in the Food and Drugs Act of Canada, which include criteria for Pseudomonas aeruginosa (0 colony-forming units/100 mL of water), was used to assess the survival of P. aeruginosa in inoculated bottled water. The effects of P. aeruginosa on the survival of Salmonella spp. in bottled water were also investigated. The methodology used in the isolation included the use of hydrophobic grid membrane filters, a resuscitation step on tryptic soy agar, and selective plating on P. aeruginosa selective agar for P. aeruginosa and on xylose lysine desoxycholate agar for salmonellae. Pseudomonas aeruginosa and salmonellae proliferated and survived in inoculated water for up to 100 days or longer. Pseudomonas aeruginosa had a synergistic effect on the survival of salmonellae, enabling them to survive for more than 140 days in double distilled water.

Canada↗

[Genetic studies of relationship between Mediterranean and Atlantic populations of loggerhead turtle Caretta caretta with mitochondrial marker].

The loggerhead turtle Caretta caretta is an endangered species in the Mediterranean. Therefore, the definition of the Mediterranean population, and their relationships to the Atlantic population is of fundamental importance. For this purpose, we have sequenced a portion of the mitochondrial cytochrome b gene to generate genetic markers. Results indicate that the Mediterranean nesting female population is genetically isolated from the Atlantic nesting female population, but loggerhead turtles of Atlantic origin were found in the West Mediterranean basin. This entry of Atlantic loggerheads in the Mediterranean confirms earlier speculations and presents special conservation problems. The Spanish swordfish longline fishery which incidentally captures large numbers of loggerheads in the West Mediterranean basin has therefore an impact on the Atlantic population. These data demonstrate the international nature of marine turtle conservation.

Animals↗

A pilot clinical and pharmacokinetic study of intracarotid cisplatin and bleomycin.

Fifteen patients with progressive primary malignant or metastatic brain tumors were treated on a clinical and pharmacokinetic study with intracarotid cisplatin and bleomycin. Toxicity was tolerable and consisted mainly of nausea and vomiting. Neurologic toxicity included focal seizures (1), leukoencephalopathy (1), and motor weakness (1). Five patients had improvement in CT scans and four patients had stabilization of disease. Recommended dosage for future clinical trials are cisplatin 60 mg/m2 and bleomycin 100 units. Pharmacokinetics of intracarotid cisplatin revealed the jugular vein concentration was twice the peripheral vein level at the end of infusion. Cisplatin is a drug which has demonstrated in vitro activity against malignant gliomas (1). Clinical trials with intravenous administration of cisplatin has shown definite, although limited antitumor activity against primary brain tumors (2,3,4) and metastatic brain tumors (5,6). To enhance its antitumor effect, cisplatin has been administered by the intracarotid route (7,8,9). The results appear encouraging, but neurological and ophthalmological toxicity may occur (8). In our initial study with intracarotid cisplatin, 35 patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation +/- chemotherapy were treated. Of 20 evaluable patients with primary tumors, 6 responded to therapy and 5 had stable disease. Five of 10 evaluable patients with brain metastases responded and 2 had stable disease. For responding primary brain tumor patients the median time to progression was 33 weeks. The recommended dose for intracarotid cisplatin was 60-75 mg/m2 administered every 3-4 weeks (7,8). Higher cisplatin doses produced more central neurological toxicity. There is limited data on the central nervous system pharmacology of cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗