Search PubMed⌕ Search

Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 307 records · Page 17Linked to original sources
PubMed1999

Cryo-electron microscopy of GDP-tubulin rings.

Rings of guanosine diphosphate (GDP)-tubulin formed in the presence of divalent cations have been studied using conventional negative stain and cryo-electron microscopy. The structure of such rings resembles that of depolymerizing microtubule ends and corresponds to an "unconstrained" conformation of tubulin in its GDP state. The use of cryo-techniques has allowed us to image the ring polymers free from dehydration and flattening artifacts. Preparations of frozen-hydrated GDP-tubulin rings are generally heterogeneous and contain a mixture of double, triple, and incomplete rings, as well as spirals and some rare single rings. Images of different polymer types can be identified and classified into groups that are then amenable for averaging and single particle reconstruction methods. Identifying the differences in tubulin structure, between straight and curve protofilaments, will be important to understand the molecular bases of dynamic instability in microtubules.

Animals↗
PubMed1999

The NAC proton treatment planning system.

A three-dimensional proton treatment planning system called PROXELPLAN has been used at the National Accelerator Centre (NAC) since October 1994. This system is entirely based on the VOXELPLAN planning system, developed at the Deutches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. The VOXELPLAN system provides the treatment planning infrastructure while the proton dose distributions are calculated using a software module that was initially developed at the Royal Marsden Hospital, UK. The proton module has been extensively modified and refined. It uses a rayline-tracing algorithm which is suitable for planning current treatments but is not sufficiently dynamic to accommodate the use of compensators. A sophisticated pencil beam algorithm is currently under development.

Algorithms↗
PubMed1999

Frequency of spinocerebellar ataxia types 1,2,3,6,7 and dentatorubral pallidoluysian atrophy mutations in Korean patients with spinocerebellar ataxia.

Autosomal dominant cerebellar ataxias (ADCAs) are a heterogeneous group of disorders characterized by degenerative symptoms in the cerebellum, spinal cord, and brain stem. Six different genes have been reported to be associated with ADCA, and the length of trinucleotide repeats of these genes is correlated with the age at onset and severity of symptoms. Although there are strong hereditary effects in these disorders, most of the studies carried out in heterogeneous populations and in small groups obscure the true incidence of these diseases. We examined the frequency of six types of ADCAs in 87 unrelated Korean patients with progressive ataxia and compared the results to the frequencies in other ethnic groups. Spinocerebellar ataxia (SCA) type 2 was the most frequent hereditary ataxia (12.6%) and types 3 and 6 accounted for 4.6% and 6.9% of ataxia patients, respectively. Dentatorubral pallidoluysian atrophy was also found in three patients (3.4%). No instances of SCA types 1 or 7 were detected. These findings show the striking contrast to the white population and a difference from Japanese findings. Our results demonstrate that dentatorubral pallidoluysian atrophy should be included in the differential diagnosis of Korean patients with spinocerebellar ataxia, and that there are strong hereditary effects in patients with ADCAs.

Case-Control Studies↗
PubMed1999

The principle of a three-staged operation in the surgery of acne scars.

BACKGROUND: Acne scars cannot be effectively corrected by a single treatment modality because of their widely varied depth and width. OBJECTIVE: We assessed the effectiveness of staged combinations of several surgical modalities in the treatment of acne scars. METHODS: Focal chemical peeling, carbon dioxide (CO2) laser, scar excision, punch grafting, and dermabrasion were used. Initially, focal chemical peeling was performed on all patients and then CO2 laser, scar excision, and punch grafts were used for deep scars. Finally, dermabrasion was done for the remaining scars. RESULTS: Seventy-five percent of patients showed excellent or good results. The degree of improvement increased as the follow-up periods and number of focal chemical peeling procedures increased and as the 3-staged operation progressed. CONCLUSION: A 3-staged operation is effective in the treatment of patients with various types of acne scars.

Acne Vulgaris↗
PubMed1999

An innovative approach to temporary hemodialysis vascular access.

The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) has set down explicit and extensive guidelines for temporary and permanent hemodialysis vascular access. It is now incumbent on the nephrologist to ensure compliance to these standards. Two of our interventional nephrologists performed 402 central venous access procedures over a 12-month period (November 1996 to October 1997) to test the hypothesis that increased control over insertion technique would improve outcome. All but eight of the procedures were successfully completed, resulting in a failure rate of 2%. The expected serious procedural complication rate outlined in the NKF-DOQI standards is 2%. Our complication rate was 0.7% if all procedures were accounted for and 0.89% for just internal jugular and subclavian catheters. We conclude that the use of interventionally trained nephrologists and strict control of technique can improve outcome in temporary vascular access procedures.

Arteriovenous Shunt, Surgical↗
PubMed1999

Metabolic and morphological stability of motoneurons in response to chronically elevated neuromuscular activity.

The purpose of this study was to determine the plasticity of spinal motoneuron size and succinate dehydrogenase activity in response to increased levels of neuromuscular activation and/or increased target size. The plantaris muscles of adult rats were functionally overloaded for one or 10 weeks via the removal of the soleus and gastrocnemius muscles bilaterally. In addition, one group of functionally overloaded rats at each time period was trained daily (1 h/day) on a treadmill. The plantaris muscle on one side in each rat was injected with the fluorescent tracer Nuclear Yellow two days prior to the end of the study to retrogradely label the associated motor pool. At one week, the plantaris weight was increased compared to control, whereas there was no change in motoneuron size. Succinate dehydrogenase activity was unaffected in either the muscle or motoneurons. At 10 weeks, the plantaris muscle weight was larger and the succinate dehydrogenase activity lower in the functionally overloaded rats compared to age-matched controls. Training further increased the hypertrophic response, whereas the succinate dehydrogenase activity returned to control levels. In contrast, mean motoneuron size and succinate dehydrogenase activity were similar among the three groups. These data indicate that overload of a specific motor pool, involving both an increase in activation and an increase in target size, had a minimal effect on the size or the oxidative potential of the associated motoneurons. Thus, it appears that the spinal motoneurons, unlike the muscle fibers, are highly stable over a wide range of levels of chronic neuromuscular activity.

Animals↗
PubMed1999

High-performance liquid chromatography study of the pharmacokinetics of various spin traps for application to in vivo spin trapping.

In vivo spin trapping is potentially a very useful tool to investigate the role of free radicals in physiologic processes and disease development. Unfortunately, knowledge on the stability and distribution of spin traps in living systems is limited. Therefore, in our study, we selected 11 acyclic and cyclic nitrone spin traps with diverse properties to determine their pharmacokinetics in mice. At varying times after intraperitoneal administration, we measured the concentration of the spin traps in the liver, heart, and blood. Our results showed that most spin traps were rapidly absorbed and were approximately evenly distributed throughout the mouse body. It was also found that most of the traps were relatively stable in vivo with more than half of the injected amount still available for spin trapping free radicals after an hour. Two of the 11 tested spin traps, however, decomposed after injection. These results indicate that for a successful in vivo spin trapping experiment, the stability of the spin trap is not of major concern, but the time course of distribution may be important.

Animals↗
PubMed1999

2-Benzyl-2-methylsuccinic acid as inhibitor for carboxypeptidase A. synthesis and evaluation.

Recently, Asante-Appiah et al. (Asante-Appiah, E.; Seetharaman, J.; Sicheri, F.; Yang, D. S.-C.; Chan, W. W.-C. Biochemistry 1997, 36, 8710 8715) reported that 2-ethyl-2-methylsuccinic acid is a highly potent inhibitor for carboxypeptidase A (CPA), a prototypic zinc protease. The X-ray crystal structure of the complex of the enzyme formed with 2-ethyl-2-methylsuccinic acid revealed that at the active site of CPA there is present a small cavity which accommodates the methyl group of the inhibitor. These investigators postulated that incorporation of a methyl group at the alpha-position to the carboxylate of existing inhibitors of CPA would improve the inhibitory potency. We have synthesized racemic and optically active 2-benzyl-2-methylsuccinic acids and evaluated their inhibitory activities for CPA to find the K(i) values to be 0.28, 0.15, and 17microM for racemic form, (R)-, and (S)-enantiomer, respectively. Contrary to the expectation, the effect on the binding affinity by the incorporation of the methyl group is minimal. The validity of the proposition that the small cavity may be utilized for the improvement of the inhibitory potency appears questionable.

Benzene Derivatives↗
PubMed1999

Uterine artery embolization for the treatment of uterine leiomyomata midterm results.

INTRODUCTION: The authors review their midterm experience with uterine artery embolization for the treatment of uterine fibroids. MATERIALS AND METHODS: Sixty patients were referred for permanent polyvinyl alcohol (PVA) foam particle uterine artery embolization during an 18-month period. Detailed clinical follow-up and ultrasound follow-up were obtained. RESULTS: Bleeding was a presenting symptom in 56 patients and pain was a presenting symptom in 47 patients. All patients underwent a technically successful embolization. One of the patients underwent unilateral embolization. Fifty-nine patients underwent bilateral embolization. Of all patients undergoing bilateral embolization, at last follow-up (mean, 16.3 months), 81% had their uterus and had moderate or better improvement in their symptoms. Ninety-two percent of these patients also had reductions in uterine and dominant fibroid volumes. Overall, the mean uterine and dominant fibroid volume reduction were 42.8% and 48.8%, respectively (mean follow-up, 10.2 months). One infectious complication that necessitated hysterectomy occurred. CONCLUSION: Uterine artery embolization for the treatment of uterine fibroids is a minimally invasive technique with low complication rates and very good clinical efficacy.

Adult↗
PubMed1999

Changes in motor evoked potentials to short-interval paired transcranial magnetic stimuli in multiple sclerosis.

OBJECTIVE: Paired transcranial magnetic stimuli (TMS) were applied in 8 multiple sclerosis (MS) patients with asymmetrical clinical signs and in 8 healthy controls to test the hypothesis that the circuits responsible for the generation and transmission of I-waves are abnormal in the former group METHODS: A figure-of-8 coil discharging through a Magstim 200/Bistim configuration delivered identical stimuli at an intensity 10% above the motor threshold of the relaxed first dorsal interosseous muscle. The interstimulus intervals (ISIs) used were varied in a pseudo-randomized fashion in steps of 0.2 ms between 1.0 and 5 ms. RESULTS: In 9 of 12 unilateral studies in the control group, a pattern of 3 peaks of increased motor evoked potential size was found at ISIs of 1.2-1.6 ms, 2.4-3.2 ms and 4.4-5.0 ms. A similar pattern was present in only 5 of 12 studies in the patients (Fisher's exact test, P = 0.1), while it was absent in all the 4 studies of the side with greater clinical involvement in patients (P = 0.01) CONCLUSION: Our results suggest that I-wave generation is more likely to be defective in MS than in normal subjects, that this defect resides in the cortex, and that it correlates with severity of physical signs.

Adult↗
PubMed1999

Fluorescent excitation transfer immunoassay for the determination of spinosyn A in water.

A fluorescent excitation transfer immunoassay for spinosyn A, a fermentation derived insect control agent, has been developed and applied to the analysis of tap water and wastewater effluent from manufacturing plants. Fluorescein (F) and tetramethylrhodamine (TMR) were chosen as donor and quencher, respectively, for the excitation transfer. Fluorescence quenching was observed from the binding of F-labeled antigen to TMR-labeled antibody. By employing nonlabeled antigen in a competitive immunoassay format, we reversed fluorescence quenching. The assay provides a limit of detection of 0. 01 ppb and a working range of 0.05-1 ppb and allows for the rapid determination of spinosyn A in water with recovery values ranging from 96% to 120%. With the exploitation of the small size of optical fibers, fluorescence from an assay volume of 24 microL could be measured without special vessels.

Anti-Bacterial Agents↗
PubMed1999

Plant low-molecular-weight phospholipase A2S (PLA2s) are structurally related to the animal secretory PLA2s and are present as a family of isoforms in rice (Oryza sativa).

Recently, we purified to homogeneity and characterized a low-molecular-weight calcium-dependent phospholipase A2 (PLA2) from developing elm seed endosperm. This represented the first purified and characterized PLA2 from a plant tissue. The full sequences of two distinct but homologous rice (Oryza sativa) cDNAs are given here. These encode mature proteins of 1 19 amino acids (PLA2-I, preceded by a 19 amino acid signal peptide) and 128 amino acids (PLA2-II. preceded by a 25 amino acid signal peptide), and were derived from four expressed sequence tag (EST) clones. Both proteins were homologous to the N-terminal amino acid sequence of the elm PLA2. They contained twelve conserved cysteine residues and sequences that are likely to represent the Ca(2+)-binding loop and active-site motif, which are characteristic of animal secretory PLA2s. A soluble PLA2s activity was purified 145 000-fold from green rice shoots. This had the same biochemical characteristics as the elm and animal secretory PLA2s. The purified rice PLA2 consisted of two proteins, with a molecular weight of 12 440 and 12 920, that had identical N-terminal amino acid sequences. This sequence was different from but homologous to the PLA2-I and PLA2-II sequences. Taken together, the results suggest that at least three different low-molecular-weight PLA2s are expressed in green rice shoots. Southern blot analysis suggested that multiple copies of such genes are likely to occur in the rice and in other plant genomes.

Amino Acid Sequence↗
PubMed1999

Determination of an optimal dosing regimen for aspirin chemoprevention of 1,2-dimethylhydrazine-induced colon tumours in rats.

In order to establish an optimal timing and duration of aspirin treatment in the chemoprevention of 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats, colon tumours were induced using an established protocol and aspirin was given in the diet at 500 p.p.m. during various stages of colon carcinogenesis. Results indicate that only aspirin treatment throughout the entire carcinogenic period significantly reduced tumour incidence and volume whereas intermittent aspirin dosing increased tumour number and/or volume, suggesting that aspirin must be used for an extended period in order to gain any chemopreventive benefit.

1,2-Dimethylhydrazine↗
PubMed1999

Binding of AR-1-144, a tri-imidazole DNA minor groove binder, to CCGG sequence analyzed by NMR spectroscopy.

The interactions of N-[2-(dimethylamino)ethyl]-1-methyl-4-[1-methyl-4-[4-formamido-1-meth ylimidazole-2-carboxamido]imidazole-2-carboxamido]imidazole-2-c arboxa mide (AR-1-144), a tri-imidazole polyamide minor groove binder, with DNA have been investigated by NMR and CD spectroscopy. A series of DNA oligonucleotides with a C/G-containing four-bp core, i.e. CCGG, CGCG, GGCC, and GCGC, have been titrated with AR-1-144 at different ratios. AR-1-144 favors the CCGG sequence. The flanking sequence of the CCGG core also influences the binding preference, with a C or T being favored on the 3'-side of the CCGG core. The three-dimensional structure of the symmetric 2:1 side-by-side complex of AR-1-144 and GAACCGGTTC, determined by NOE-constrained NMR refinement, reveals that each AR-1-144 binds to four base pairs, i.e. at C5-G6-G7-T8, with every amide-imidazole unit forming two potential hydrogen bonds with DNA. The same DNA binding preference of AR-1-144 was also confirmed by circular dichroism spectroscopy, indicating that the DNA binding preference of AR-1-144 is independent of concentration. The cooperative binding of an AR-1-144 homodimer to the (purine)CCGG(pyrimidine) core sequence appears to be weaker than that of the distamycin A homodimer to A/T sequences, most likely due to the diminished hydrophobic interactions between AR-1-144 and DNA. Our results are consistent with previous footprinting data and explain the binding pattern found in the crystal structure of a di-imidazole drug bound to CATGGCCATG.

Base Sequence↗
PubMed1999

Olanzapine transfer by human placenta.

1. The present study assessed the human transplacental transport of olanzapine, a new antipsychotic drug effective in the treatment of schizophrenia. 2. Using the normal-term placenta perfused single cotyledon system, we show that: (i) 5-14% of labelled olanzapine crosses from the maternal to foetal compartments in 4 h; (ii) transport depends significantly on binding characteristics, especially of albumin; (iii) no oxidative metabolites of olanzapine appear in the placental perfusate over 4 h; and (iv) approximately 17% of olanzapine, on average, is converted to the glucuronide, which is transferred by the placenta at a rate slightly slower than the parent drug.

Antipsychotic Agents↗
PubMed1999

Alpha4 but not alpha3 and alpha7 nicotinic acetylcholine receptor subunits are lost from the temporal cortex in Alzheimer's disease.

Neuronal nicotinic acetylcholine receptors labelled with tritiated agonists are reduced in the cerebral cortex in Alzheimer's disease (AD), but to date it has not been demonstrated which nicotinic receptor subunits contribute to this deficit. In the present study, autopsy tissue from the temporal cortex of 14 AD cases and 15 age-matched control subjects was compared using immunoblotting with antibodies against recombinant peptides specific for alpha3, alpha4, and alpha7 subunits, in conjunction with [3H]epibatidine binding. Antibodies to alpha3, alpha4, and alpha7 produced one major band on western blots at 59, 51, and 57 kDa, respectively. [3H]Epibatidine binding and alpha4-like immunoreactivity (using antibodies against the extracellular domain and cytoplasmic loop of the alpha4 subunit) were reduced in AD cases compared with control subjects (p < 0.02) and with a subgroup of control subjects (n = 9) who did not smoke prior to death (p < 0.05) for the former two parameters. [3H]Epibatidine binding and cytoplasmic alpha4-like immunoreactivity were significantly elevated in a subgroup of control subjects (n = 4) known to have smoked prior to death (p < 0.05). There were no significant changes in alpha3- or alpha7-like immunoreactivity associated with AD or tobacco use. The selective involvement of alpha4 has implications for understanding the role of nicotinic receptors in AD and potential therapeutic targets.

Aged↗
PubMed1999

The influence of gatekeeping and utilization review on patient satisfaction.

OBJECTIVE: To examine the influence of utilization review and denial of specialty referrals on patient satisfaction with overall medical care, willingness to recommend one's physician group to a friend, and desire to disenroll from the health plan. DESIGN: Two cross-sectional questionnaires: one of physician groups and one of patient satisfaction. SETTING: Eighty-eight capitated physician groups in California. PARTICIPANTS: Participants were 11,710 patients enrolled in a large California network-model HMO in 1993 who received care in one of the 88 physician groups. MEASUREMENTS AND MAIN RESULTS: Our main measures were how groups conducted utilization review for specialty referrals and tests, patient-reported denial of specialty referrals, and patient satisfaction with overall medical care. Patients in groups that required preauthorization for access to many types of specialists were significantly (p </=.001) less satisfied than patients in groups that had few preauthorization requirements, even after adjusting for patient and other group characteristics. Patients who had wanted to see a specialist in the previous year but did not see one were significantly less satisfied than those who had wanted to see a specialist and actually saw one (p <.001). In addition, patients who did not see a specialist when desired were more likely to want to disenroll from the health plan than patients who saw the specialist (40% vs 18%, p </=.001) and more likely not to recommend their group to a friend (38% vs 13%, p </=.001). CONCLUSIONS: Policies that limited direct access to specialists, and especially denial of patient-desired referrals, were associated with significantly lower patient satisfaction, increased desire to disenroll, and lower likelihood of recommending the group to a friend. Health plans and physician groups need to take these factors into account when designing strategies to reduce specialty care use.

Adolescent↗