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Biomedical subjects

J H Miller

Publications and source records attributed to J H Miller.

At least 127 records · Page 7Linked to original sources
PubMed1996

The scintigraphic appearance of childhood moyamoya disease on cerebral perfusion imaging.

OBJECTIVE: This study was performed to evaluate the role of single photon emission computed tomography (SPECT) perfusion imaging in the evaluation of patients with moyamoya disease. MATERIALS AND METHODS: Five patients (four female, one male) were studied utilizing iodine-123 iodoamphetamine or technetium-99m hexamethylpropyleneamine oxime SPECT. The data were reconstructed into axial, coronal and sagittal sections for review, and compared with CT, MR and/or angiographic images. RESULTS: All five patients had significant perfusion defects. These areas of vascular compromise were seen to cross normal vascular territories, and were greater in number and extent than seen on anatomic sectional imaging. CONCLUSION: Patients with moyamoya disease have a recognizable pattern of scintigraphic perfusion deficits which should be identified by pediatric imaging physicians. SPECT perfusion studies should be performed in conjunction with other imaging modalities (CT, MR or angiography).

Adolescent↗
PubMed1996

Development of a liquid chromatographic method for the control of related substances in chlorprothixene hydrochloride.

The development of a reversed-phase liquid chromatographic method, using a mobile phase containing a mixture of anion and cation ion-pairing agents and a base-deactivated octyldecylsilyl column as stationary phase, is described for the control of all known impurities in (Z)-chlorprothixene hydrochloride (bulk drug). Validation of the method showed it to be reproducible, selective for both (Z) chlorprothixene hydrochloride and its E-isomer, accurate and linear over the concentration range of analysis with a limit of detection of 0.3 microgram ml-1.

Antipsychotic Agents↗
PubMed1996

Interlaboratory study of the analysis of ampicillin by liquid chromatography.

A liquid chromatographic method for the analysis of ampicillin was examined in a collaborative study involving seven laboratories. The method included an isocratic part, which is used in the assay. The isocratic part is similar to the assay method for ampicillin of the US Pharmacopeia XXIII Revision. When the isocratic part is combined with gradient elution, the method is suitable for purity control. Six samples of ampicillin (anhydrous, trihydrate and sodium salt) with varying purity were analysed. The main component and related substances were determined. An analysis of variance proved the absence of consistent laboratory bias. The laboratory-sample interaction was significant. Estimates of the repeatability and reproducibility of the method, expressed as standard deviations of the result of the determination of ampicillin, were calculated to be about 0.9 and 1.1 respectively.

Ampicillin↗
PubMed1996

Octreotide diminishes luminal nutrient transport activity, which is reversed by epidermal growth factor.

BACKGROUND: Octreotide (SMS) is a somatostatin analogue utilized in patients with short bowel syndrome (SBS) to decrease output. It may inhibit small bowel adaptation by blocking the secretion of trophic hormones such as epidermal growth factor (EGF). This study delineates the effects of SMS and EGF on nutrient transport in SBS. METHODS: One week after 70% jejunoileal resection, 20 New Zealand White rabbits (2 kg) received subcutaneous infusions of saline or EGF (1.5 micrograms/kg/hr) and injections of saline or SMS s.q.b.i.d. The study groups were EGF/saline, saline/saline, saline/SMS, and EGF/SMS. After 7 days of infusion, intestinal brush border membrane vesicles were prepared and nutrient transport measured. RESULTS: SMS reduced active nutrient transport. Kinetics confirmed this was secondary to a reduction in functional carriers in the brush border membrane, without a change in carrier affinity. The coinfusion of EGF ameliorated this effect. On an individual basis, EGF alone did not significantly increase nutrient transport, but when taken as a group, nutrients transport was upregulated 26%. CONCLUSIONS: SMS is detrimental to small bowel adaptation. EGF reverses this effect and may benefit patients with SBS who require SMS to control high intestinal output.

Amino Acids↗
PubMed1996

Sequential alterations in gut mucosal amino acid and glucose transport after 70% small bowel resection.

BACKGROUND: Studies in animals with short bowel syndrome (SBS) suggest that up-regulation of nutrient transporter activity occurs as an adaptive response to the loss of absorptive area. It is unclear, however, whether nutrient transport is altered at the cell membrane in SBS. The purpose of this study is to clarify amino acid and glucose transport in small intestinal luminal mucosa after 70% small bowel resection in rabbits. METHODS: New Zealand white rabbits underwent 70% jejunoileal resection (n = 27) or a sham operation (n = 19). Brush border membrane vesicles were prepared from small intestinal mucosa at 1 week, 1 month, and 3 months by magnesium aggregation-differential centrifugation. Transport of L-glutamine, L-alanine, L-leucine, L-arginine, and D-glucose was assayed by a rapid mixing-filtration technique. RESULTS: We observed no difference in uptake of all amino acids and glucose at 1 week. The uptake of amino acids and glucose was decreased by 20% to 80% in animals with SBS at 1 month. By 3 months all uptake values except that of glucose returned to normal. Kinetic studies of the system B transporter for glutamine indicate that the decrease in uptake at 1 month was caused by a reduction in the Vmax (1575 +/- 146 versus 2366 +/- 235, p < 0.05) consistent with a decrease in the number of functional carriers on the brush border membrane. CONCLUSIONS: In addition to the anatomic loss of absorptive area after massive bowel resection, alterations in enterocyte transport function may be responsible for malabsorption in patients with SBS.

Amino Acids↗
PubMed1996

Femorofemoral crossover grafts for claudication: a safe and reliable procedure.

OBJECTIVE: To evaluate the role of femorofemoral crossover grafts in patients with disabling claudication. DESIGN: Retrospective study. SETTING: University hospital. MATERIALS: Two hundred and eleven patients with iliac artery disease undergoing femorofemoral crossover grafts for disabling claudication. CHIEF OUTCOME MEASURES: Perioperative mortality, follow-up cumulative graft patency, limb loss, survival, graft infection and false aneurysm formation were evaluated to determine the immediate and long-term outcome of the procedure. MAIN RESULTS: Primary and secondary graft patency at 5 years was 72% and 89% respectively. There were no perioperative deaths (zero 30 day mortality). Dacron was used in 66 patients (31%) and PTFE in 145 (69%). There were no differences in patency between the two graft materials but eight Dacron grafts (12.1%) were removed because of complications (false aneurysm or infection) compared to four PTFE grafts (2.7%) (p < 0.001 Chi-square). Five patients (2%) have undergone a major lower limb amputation. Forty-one patients (19%) have required subsequent inflow procedures which represents a cumulative need for inflow of 5% per year. CONCLUSIONS: Femorofemoral crossover grafts are a safe and reliable procedure in patients with disabling claudication caused by unilateral iliac artery disease.

Adult↗
PubMed1996

Modeling DNA hydration: comparison of calculated and experimental hydration properties of nuclic acid bases.

Hydration properties of individual nucleic acid bases were calculated and compared with the available experimental data. Three sets of classical potential functions (PF) used in simulations of nucleic acid hydration were juxtaposed: (i) the PF developed by Poltev and Malenkov (PM), (ii) the PF of Weiner and Kollman (WK), which together with Jorgensen's TIP3P water model are widely used in the AMBER program, and (iii) OPLS (optimized potentials for liquid simulations) developed by Jorgensen (J). The global minima of interaction energy of single water molecules with all the natural nucleic acid bases correspond to the formation of two water-base hydrogen bonds (water bridging of two hydrophilic atoms of the base). The energy values of these minima calculated via PM potentials are in somewhat better conformity with mass-spectrometric data than the values calculated via WK PF. OPLS gave much weaker water-base interactions for all compounds considered, thus these PF were not used in further computations. Monte Carlo simulations of the hydration of 9-methyladenine, 1-methyluracil and 1-methylthymine were performed in systems with 400 water molecules and periodic boundary conditions. Results of simulations with PM potentials give better agreement with experimental data on hydration energies than WK PF. Computations with PM PF of the hydration energy of keto and enol tautomers of 9-methylguanine can account for the shift in the tautomeric equilibrium of guanine in aqueous media to a dominance of the keto form in spite of nearly equal intrinsic stability of keto and enol tautomers. The results of guanine hydration computations are discussed in relation to mechanisms of base mispairing errors in nucleic acid biosynthesis. The data presented in this paper along with previous results on simulation of hydration shell structures in DNA duplex grooves provide ample evidence for the advantages of PM PF in studies of nucleic-acid hydration.

Base Composition↗
PubMed1996

Detection of bone lesions in Langerhans cell histiocytosis: complementary roles of scintigraphy and conventional radiography.

PURPOSE: This research was undertaken to determine the relative sensitivity of scintigraphic and radiographic bone survey examinations in detecting bone lesions in various regions of the skeleton in patients with a histopathologic diagnosis of Langerhans cell histiocytosis (LCH). PATIENTS AND METHODS: Radionuclide skeletal scintigraphy (RNSS) and x-ray skeletal surveys (XRSS) of 42 children with a histopathologic diagnosis of LCH were evaluated retrospectively. RESULTS: Of the 191 lesions detected in 42 patients, 36 (19%) were missed on RNSS and 55 (29%) were missed on XRSS. Most of the missed lesions on RNSS were in the skull (26 of 36). XRSS also missed 13 skull lesions seen on RNSS. Most of the lesions missed on XRSS were in the ribs (20 of 30 rib lesions), whereas RNSS identified 29 of them. XRSS also missed 13 of 38 lesions in the spine and pelvis, while RNSS demonstrated all of them. Both modalities showed comparable sensitivity in the extremities. CONCLUSION: RNSS has a greater value in detecting sites of bone involvement with LCH than reported previously. RNSS is more sensitive than XRSS in detecting histiocytic lesions in the ribs, spine and pelvis and less sensitive in identifying lesions in the skull.

Bone Diseases↗
PubMed1996

Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage.

We have cloned the human mutY gene (hMYH) from both genomic and cDNA libraries. The human gene contains 15 introns and is 7.1 kb long. The 16 exons encode a protein of 535 amino acids that displays 41% identity to the Escherichia coli protein, which provides an important function in the repair of oxidative damage to DNA and helps to prevent mutations from oxidative lesions. The human mutY gene maps on the short arm of chromosome 1, between p32.1 and p34.3.

Amino Acid Sequence↗
PubMed1996

Spontaneous mutators in bacteria: insights into pathways of mutagenesis and repair.

Mutators are cells that have a higher mutation rate than the wild type. Such mutators have been extensively studied in bacteria, and this has led to the elucidation of a number of important DNA repair pathways, as well as revealing new pathways of mutagenesis. Repair defects in humans that lead to mutator phenotypes are responsible for a number of cancer susceptibilities. In some cases, these repair systems are the close counterparts of the equivalent bacterial repair system. Therefore, characterizing bacterial mutators and the repair systems that are deficient can aid in discovering the human homolog of these systems.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

The relevance of bacterial mutators to understanding human cancer.

The study of mutator strains of bacteria has elucidated new systems and pathways of mutagenesis and led to the defining of human counterparts to these systems. In addition to previous work that defined the mismatch repair system, newer studies have revealed a repair pathway for oxidative lesions, as well as demonstrating that mistranslation can increase mutation rates. Defects in the human repair pathways are involved in increased cancer susceptibility as well as a mutator character.

Bacteria↗
PubMed1995

Monoclonal antibodies differentially reactive with native and reductively modified Bowman-Birk protease inhibitor.

Bowman-Birk protease inhibitor (BBI) is a potent anticarcinogen that suppresses malignant transformation at nanomolar concentrations. Small amounts of BBI in its native form can be measured by immunoassay using specific monoclonal antibodies (MAbs); however, the MAbs currently available are not capable of detecting BBI metabolites in human body fluids. To develop new reagents for the study of BBI exposure and pharmacokinetics, we produced four MAbs, designated 3B6, 3E3, 4H8 and 5G2, from hybridomas derived from a mouse immunized with reductively modified BBI. The epitopes recognized by the four MAbs were characterized using BBI in its native form or modified by different methods. MAb 3B6 reacted with native BBI. Partial reduction of BBI with 720 Gy of gamma radiation in an oxygen-free solution of 100 mM formate increased the reactivity of BBI with 3B6; however, extensive reduction of BBI with 100 mM DL-dithiothreitol (DTT) completely abolished this antigenic reactivity. In contrast, the other three MAbs reacted with BBI molecules that had been reduced either with 720 Gy of radiation in formate solution or with DTT. Alkylation of the radiochemically reduced BBI with N-ethylmaleimide further increased the reactivity of BBI with 3E3, 4H8 and 5G2, possibly by preventing the formation of new disulfide bonds within the BBI molecules. The binding of 4H8 and 5G2 to BBI antigen was inhibited by the binding of 3E3, and vice versa. Thus, the epitopes recognized by 3E3, 4H8 and 5G2 are probably located close to one another on the reduced BBI molecules. These three MAbs were able to react with BBI metabolites in urine samples collected from volunteers after oral administration of BBI. The ability of these MAbs to detect BBI metabolites indicates that BBI may be reductively modified in vivo and these MAbs may be useful reagents for monitoring the uptake of BBI into human tissues in cancer chemoprevention studies with BBI.

Animals↗
PubMed1995

Theoretical analysis of DNA intrastrand cross linking by formation of 8,5'-cyclodeoxyadenosine.

Formation of intramolecular cross links by addition of C(5') deoxyribose radicals to the C(8)-N(7) double bond of an attached adenine base was analyzed by ab initio quantum-chemical methods. Conformational preferences that influence the stereospecificity of the reaction were investigated. A good correlation was found between the ratio of experimental yields of R and S stereoisomers of 8,5'-cyclodeoxyadenosine and the relative energy of conformations of the C(5') radical that are precursors to these isomers. Molecular mechanics based on the AMBER force field was used to model the effect of 8,5'-cyclodeoxyadenosine on the conformation of the DNA dodecamer d(CGCGAATTCGCG)2 with the lesion at the A6 position. The R and S stereoisomers of the intrastrand cross link cause comparable levels of DNA distortion with the major conformational changes occurring in backbone torsional angles at the site of the lesion.

Base Sequence↗
PubMed1995

Influence of a vein cuff on polytetrafluoroethylene grafts for primary femoropopliteal bypass.

A retrospective investigation was performed to study the benefit obtained from a vein cuff inserted at the distal anastomosis of a primary femoropopliteal bypass graft with polytetrafluoroethylene (PTFE). When PTFE was preferred to vein an attempt was made to assess whether there was subsequent use for the spared vein. A series of 559 primary PTFE bypasses was studied and found to have a cumulative patency rate of 62 per cent at 36 months. Subgroups were also studied for a similar period. In the above-knee position there was no difference in the primary patency rate of PTFE with or without a cuff at 36 months (69 versus 68 per cent, P = 0.89). Below the knee, grafts with a cuff had a better 36-month patency rate than those without (57 versus 29 per cent, P = 0.01). Cuffed PTFE for claudication had a better patency rate than that for threatened limbs at 36 months (68 versus 60 per cent, P = 0.03). Thrombectomy of occluded cuffed PTFE grafts improved the 36-month patency rate from 64 to 74 per cent. The limb salvage rate at 36 months was 97 per cent for claudication and 89 per cent for threatened limbs with cuffed PTFE. Occlusion of cuffed PTFE was associated with preservation of outflow in 91 (51 per cent) of 179 cases, permitting subsequent graft thrombectomy or insertion of a new bypass. Spared vein was rarely used to salvage an occluded PTFE graft, and was associated with poor patency and a high amputation rate. Although this study does not support the use of PTFE for the primary graft, PTFE with a vein cuff interposed at the distal anastomosis is a reasonable substitute when vein is not available.

Adult↗