Dopamine [beta]-hydroxylation in diabetes and diabetic autonomic neuropathy

Dopamine [beta]-hydroxylase (DBH) has been studied in healthy subjects and diabetic patients, some of whom had autonomic neuropathy. DBH was assayed by a recently described in vivo tritium release method (10,11). Dopamine specifically labeled in the [beta] position, [[beta]-3H]DA, was given intravenously, and the time course of tritiated water (THO) release into the total body water was measure as an index of DBH activity in sympathetic neurons. We simultaneously assayed [3H]norepinephrine metabolite excretion.The DBH activity of patients with autonomic neuropathy as a group did not differ significantly from that of diabetics without neuropathy or healthy controls. Our data do not support the suggestion (7) that a deficit in DBH activity is responsible for sympathetic neuronal dysfunction in diabetic autonomic neuropathy. This syndrome thus differs from idiopathic orthostatic hypotension in which condition there is an impairment in the ability of sympathetic neurons to hydroxylate dopamine (9).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24287/1/0000553.pd

Improved regional selectivity of hepatic arterial mitomycin by starch microspheres

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109929/1/cptclpt1983163.pd

Constant intraperitoneal 5‐fluorouracil infusion through a totally implanted system

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109794/1/cptclpt198412.pd

High-performance liquid chromatographic method for the determination of bromodeoxyuridine and its major metabolite, bromouracil, in biological fluids

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25867/1/0000430.pd

The Wolf-Rayet Content of M33

Wolf-Rayet stars (WRs) are evolved massive stars, and the relative number of WC-type and WN-type WRs should vary with metallicity, providing a sensitive test of stellar evolutionary theory. The observed WC/WN ratio is much higher than that predicted by theory in some galaxies but this could be due to observational incompleteness for WN-types, which have weaker lines. Previous studies of M33's WR content show a galactocentric gradient in the relative numbers of WCs and WNs, but only small regions have been surveyed with sufficient sensitivity to detect all of the WNs. Here we present a sensitive survey for WRs covering all of M33, finding 55 new WRs, mostly of WN type. Our spectroscopy also improves the spectral types of many previously known WRs, establishing in one case that the star is actually a background quasar. The total number of spectroscopically confirmed WRs in M33 is 206, a number we argue is complete to approximately 5%, with most WRs residing in OB associations, although approximately 2% are truly isolated. The WC/WN ratio in the central regions (<2 kpc) of M33 is much higher than that predicted by the current Geneva evolutionary models, while the WC/WN ratios in the outer regions are in good accord, as are the values in the SMC and LMC. The WC/WN ratio and the WC subtype distribution both argue that the oxygen abundance gradient in M33 is significantly larger than found by some recent studies, but are consistent with the two-component model proposed by Magrini et al.Comment: ApJ, in pres

Analysis of bromodeoxyuridine incorporation into DNA: Comparison of gas chromatographic/mass spectrometric, CsCl gradient sedimentation, and specific radioactivity methods

A sensitive new method for the quantitation of 5-bromodeoxyuridine (BrdUrd) incorporated into DNA by GC/MS analysis of enzymatically released Thy and bromouracil (BrUra) is presented. The hydrolysis procedure was characterized and found to give uniform results when sample size was 1-10 [mu]g DNA and incubation time for DNA digestion was between 40 min and 16 h. Samples of DNA containing 3H-labeled BrdUrd were analyzed in parallel by the GC/MS technique and by specific radioactivity and buoyant density measurements, in order to compare the three methods. The GC/MS procedure gave values for percentage replacement of Thy by BrUra which were higher than those obtained by specific activity and lower than those obtained by buoyant density. This GC/MS method can detect 1% replacement in a 1-[mu]g DNA sample, equivalent to approximately 105 cells or 0.1 mg tissue, and will permit sensitive and quantitative analysis of the presence of this chemotherapeutic agent/radiosensitizer in cellular DNA from biopsy samples of normal or tumor tissue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26801/1/0000357.pd

Steady‐state pharmacokinetics of delavirdine in HIV‐positive patients: Effect on erythromycin breath test

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109837/1/cptclpt199754.pd

Divergent patterns of incorporation of bromodeoxyuridine and iododeoxyuridine in human colorectal tumor cell lines

Using a panel of four human colorectal tumor (HCT) cell lines, we have quantitatively characterized the incorporation of bromodeoxyuridine (BrdUrd) and iododeoxyuridine (IdUrd) into DNA, both as individual agents and in combination with fluoropyrimidines. The intrinsic ability of these cell lines to incorporate BrdUrd, as reflected by the concentration required to achieve half- maximal incorporation, varied almost 4-fold across this panel, from 1.6 [mu]M for HuTu80 cells to 6.1 [mu]M for HT29 cells. Three of the four cell lines (HT29, SW480, SW620) responded to fluoropyrimidines as expected, displaying 100-150% increases in BrdUrd incorporation when combined with growth inhibitory concentrations of fluorouracil (FUra). In contrast, neither FUra nor fluorodeoxyuridine (FdUrd) was able to increase BrdUrd incorporation in HuTu80 cells by more than 25%, even in the presence of 100 [mu]M leucovorin. IdUrd incorporation was modulated to a substantially higher degree in both HT29 and HuTu80 cell lines. Finally we demonstrate the feasibility of a technique for evaluating the net effect of fluoropyrimidine treatments on de novo thymidine nucleotide production in a single specimen, using a combination of normotopic and stable-isotope labeled BrdUrd. We propose that this approach may be useful in evaluating the response of an individual tumor to fluoropyrimidines in vivo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29276/1/0000335.pd

Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization

PURPOSE. The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). METHODS. Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 x 3-and 6 x 6-mm(2) scans were obtained on both instruments. The 3 x 3-mm(2) SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 x 6-mm(2) SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 x 3-mm(2) scans and twice in the 6 x 6-mm(2) scans. Choroidal neovascularization was excluded if not fully contained within the 3 x 3-mm(2) scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. RESULTS. Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 x 3-mm(2) scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm(2), respectively (P = 0.047). For the 6 x 6-mm(2) scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm(2) (P = 0.003). CONCLUSIONS. The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 x 6-mm(2) scans.Carl Zeiss Meditec, Inc.National Eye InstituteResearch to Prevent Blindness, Inc. (New York, NY)National Eye Institute Center Core GrantCAPES Foundation, Ministry of Education of Brazil (Brasilia, Brazil)German Research FoundationUniv Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilUniv Washington, Dept Bioengn, Seattle, WA 98195 USACarl Zeiss Meditec Inc, Adv Dev, Dublin, CA USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilNational Eye Institute: R01EY024158National Eye Institute Center Core Grant: P30EY014801German Research Foundation: SCHA 1869/1-1Web of Scienc

Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms

PURPOSE. To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. METHODS. Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 x 3-mm and 6 x 6-mm scans. The complex optical microangiography (OMAG(C)) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 mu m below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. RESULTS. Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 x 3-mm (P = 0.61, paired t-test) and 6 x 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 x 3-mm (P = 0.41, paired t-test) and 6 x 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 3 3-mm scans (P = 0.011, paired sample t-test) and the 6 x 6-mm scans (P = 0.021, paired t-test). CONCLUSIONS. The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.Carl Zeiss Meditec, Inc. (Dublin, CA)National Eye InstituteResearch to Prevent Blindness, Inc., New York, New YorkNational Eye Institute Center Core GrantCAPES Foundation, Ministry of Education of Brazil, Brasilia-BrazilGerman Research Foundation (DFG)Research to Prevent BlindnessUniv Washington, Dept Bioengn, 3720 NE 15th Ave, Seattle, WA 98195 USAUniv Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilCarl Zeiss Meditec Inc, Adv Dev, Dublin, CA USAUniv Washington, Dept Ophthalmol, 3720 NE 15th Ave, Seattle, WA 98195 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilNational Eye Institute: R01EY024158National Eye Institute Center Core Grant: P30EY014801German Research Foundation (DFG): SCHA 1869/1-1Web of Scienc