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Biomedical subjects

C Kim

Publications and source records attributed to C Kim.

At least 19 recordsLinked to original sources

Isolation of ALP, a novel divergent murine CC chemokine with a unique carboxy terminal extension.

Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue and play important roles in many disease processes. Chemokines are divided into two major groups, CC or CXC, based on their sequence around the amino terminal cysteines. We report here, the isolation of a novel murine CC chemokine termed ALP for its amino terminal peptide sequence. This novel chemokine is distantly related to other CC chemokines (37% identity with murine Exodus-1/LARC/Mip-3alpha), but has a unique carboxy terminal extension. It is expressed preferentially in testis, heart, and liver, which is atypical for CC chemokines.

Amino Acid Sequence

Apoptotic human lymphocytes have diminished CD4 and CD8 receptor expression.

We used quantitative multiparameter flow cytometric assays to simultaneously detect viable, apoptotic, and necrotic human peripheral blood mononuclear cells (PBMC) and immunophenotyped lymphocyte subsets within the PBMC. Apoptosis was induced by a spectrum of treatments, including camptothecin, cisplatin, dexamethasone, hyperthermia, staurosporine, and etoposide in anti-CD3 mAb-stimulated cells and by cyclohexamide in both quiescent and stimulated cells; apoptosis in the latter was augmented by anti-fas mAb. We found that CD4(+) and CD8(+) cells were significantly underrepresented in the apoptotic PBMC and that the percentage of CD4(+) and CD8(+) PBMC each markedly decreased as apoptosis increased. This suggested that surface expression of these receptors was lessened on apoptotic CD4(+) and CD8(+) cells. This was directly confirmed by observation of sorted CD4(+) PBMC. This analysis of a wide variety of apoptotic stimuli demonstrates that diminished CD4 and CD8 surface receptor expression is a common feature of human T lymphocyte apoptosis.

Apoptosis

Meta-analysis of exercise testing to detect coronary artery disease in women.

To determine the accuracy of the exercise electrocardiogram (ECG), exercise thallium, and exercise echocardiogram (echo) for the diagnosis of coronary artery disease in women, English language studies published between 1966 and 1995 were identified through a MEDLINE search. Studies that contained data on at least 50 women who underwent both an exercise test and coronary angiography were examined. Studies were reviewed for sensitivity, specificity, and methodologic characteristics by 2 independent reviewers. Nineteen studies met the inclusion criteria for exercise electrocardiography, 5 studies for exercise thallium, and 3 studies for exercise echo. The exercise ECG had a weighted mean sensitivity, specificity, and a likelihood ratio (LR) of 0.61 (95% confidence intervals 0.54 to 0.68), 0.70 (0.64 to 0.75), (+) LR 2.25 (1.84 to 2.66), (-) LR 0.55 (0.47 to 0.62), respectively. The exercise thallium had a weighted mean sensitivity, specificity, and LRs of 0.78 (0.72 to 0.83), 0.64 (0.51 to 0.77), (+) LR 2.87 (1.0 to 4.96), (-) LR 0.36 (0.27 to 0.45). The exercise echo had a weighted mean sensitivity, specificity, and LRs of 0.86 (0.75 to 0.96), 0.79 (0.72 to 0.86), (+) LR 4.29 (2.93 to 5.65), (-) LR 0.18 (0.05 to 0.31). Thallium subset analysis revealed that studies using planar imaging were more specific than those using tomographic imaging. Thus, currently available exercise tests are only moderately sensitive and specific for the diagnosis of coronary artery disease in women.

Coronary Angiography

Cloning of BRAK, a novel divergent CXC chemokine preferentially expressed in normal versus malignant cells.

Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue and play important roles in many disease processes. Chemokines are divided into two major groups, CC or CXC, based on their sequence around the amino terminal cysteines. We report the PCR cloning of a novel human chemokine termed BRAK for its initial isolation from breast and kidney cells. This novel chemokine is distantly related to other CXC chemokines (30% identity with MIP-2alpha and beta) and shares several biological activities. BRAK is expressed ubiquitously and highly in normal tissue. However, it was expressed in only 2 of 18 cancer cell lines. BRAK is located on human chromosome 5q31.

Amino Acid Sequence

Drug release from drug-polyanion complex tablets: poly(acrylamido-2-methyl-1-propanesulfonate sodium -co- methyl methacrylate).

A new erodible, anionic carrier for cationic drugs has been synthesized for oral drug delivery systems. The release properties of tablets prepared from this new material, poly(acrylamido-2-methyl-1-propanesulfonate sodium -co- methyl methacrylate) (PAMPSNa/MMA), are discussed. Pseudo-linear release profiles were obtained and the hydrophobicities of both the polymeric carrier and the bound drugs were found to be an important controlling factor in determining the slopes of these release profiles. The effect of the tablet geometry on the shape of the release profiles was also investigated and tablet thickness was demonstrated to be another key parameter controlling both the linearity of the release profiles, as well as the duration of drug release. The release kinetics are strongly dependent on the drug solubility rather than on the type of amine in the drug (i.e. secondary and tertiary amines). The release of drugs from tablets of drug-PAMPSNa/MMA complexes were well described by the dissociation/erosion mechanism.

Algorithms

unc-45 gene of Caenorhabditis elegans encodes a muscle-specific tetratricopeptide repeat-containing protein.

The unc-45 gene of the nematode, Caenorhabditis elegans, is essential for muscle organization and embryonic development. Genetic evidence suggests the unc-45 gene product controls muscle thick filament assembly. We report here on the determination of the gene's chromosomal location and the isolation and sequencing of its cDNA. The amino terminus of the predicted unc-45 protein contains three tandem repeats that belong in the tetratricopeptide repeat family. Tetratricopeptide motifs have been shown to be involved in protein interactions, and some of the closest homologues have chaperone-like activity. The carboxy terminus of the protein has homology with the related fungal proteins, CRO1 and She4p, which have been postulated to play a role in assembly of or interactions with a cytoplasmic myosin. We have also determined the sequence of the homologous gene from C. briggsae, which demonstrates a high level of conservation. We show that the unc-45 gene promoter can drive reporter gene expression, which is limited to muscle tissues (pharyngeal, body wall, vulval, and anal muscles), consistent with a role for the unc-45 gene in muscle development or function.

Amino Acid Sequence

Diagnosis of suspected coronary artery disease in women: a cost-effectiveness analysis.

BACKGROUND: The optimal strategy for the diagnosis of coronary artery disease (CAD) in women is not well defined. We compared the cost-effectiveness of several strategies for diagnosing CAD in women with chest pain. METHODS: We performed decision and cost-effectiveness analyses with simulations of 55-year-old ambulatory women with chest pain. With a Markov model, simulations of patients underwent exercise electrocardiography, exercise testing with thallium scintigraphy, exercise echocardiography, angiography, or no workup. RESULTS: Diagnosis with angiography cost less than $17, 000 per quality-adjusted life-year compared with exercise echocardiography if the patient had definite angina and less than $76,000 per life-year if she had probable angina. If she had nonspecific chest pain, diagnosis with exercise echocardiography increased life-years compared with no testing. CONCLUSIONS: Cost-effectiveness of first-line diagnostic strategy for diagnosis of CAD in women varies mostly according to pretest probability of CAD. Diagnosis of coronary artery disease with angiography is cost-effective in 55-year-old women with definite angina. In 55-year-old women with probable angina, diagnosis with angiography would increase quality-adjusted life-years but significantly increase costs. Use of exercise echocardiography as a first-line diagnosis for CAD is cost effective in 55-year-old women with probable angina and nonspecific chest pain.

Angina Pectoris

Long-term brimonidine therapy in glaucoma patients with apraclonidine allergy.

PURPOSE: To report the use of brimonidine in patients with a documented ocular allergy to apraclonidine. METHODS: We conducted a prospective, open-label study on the use of long-term brimonidine therapy in 57 patients with chronic glaucoma with documented allergy to apraclonidine. The study patients were placed on brimonidine tartrate 0.2%, 1 drop three times daily in one or both eyes, either as additive therapy to a medical regimen devoid of apraclonidine for further lowering of intraocular pressure (25 patients) or as a replacement for apraclonidine at the time of diagnosis of apraclonidine ocular allergy for maintenance of intraocular pressure control (32 patients). Clinical symptoms and signs of ocular allergy to brimonidine were monitored for up to 18 months. RESULTS: During the treatment period of up to 18 months, six (10.5%) of 57 patients developed slit-lamp biomicroscopic findings and subjective symptoms of an ocular allergic reaction that led to discontinuation of brimonidine treatment. All six patients developed ocular allergy to topical brimonidine 0.2% during the first 4 months of therapy. The addition of brimonidine 0.2% topical medication or the replacement of apraclonidine with brimonidine resulted in a significant decrease in mean intraocular pressure from 20.5+/-5.3 to 16.5+/-4.2 mm Hg (P < .0001) at the mean treatment period of 10.6+/-4.6 months (range, 0.5 to 18.0 months in all 57 patients: 5 to 18 months in the 51 patients without brimonidine allergy and 0.5 to 3.8 months in the six patients who developed brimonidine allergy. CONCLUSIONS: The incidence of ocular allergy after the use of brimonidine 0.2% topical medication for up to 18 months was 10.5% in patients with a documented history of apraclonidine allergy. Therefore, it is generally safe as well as efficacious to administer brimonidine to patients with an ocular allergy to apraclonidine.

Adrenergic alpha-Agonists

The additive effect of latanoprost to maximum-tolerated medications with low-dose, high-dose, or no pilocarpine therapy.

OBJECTIVE: To assess the efficacy of latanoprost additive therapy in patients with intraocular pressure (IOP) out of control while taking maximum-tolerated medications and to determine whether pilocarpine therapy has a dose-dependent adverse effect on the efficacy of latanoprost therapy. DESIGN: Noncomparative case series. PARTICIPANTS: Sixty-one eyes of 61 patients with chronic glaucoma with IOP out of control while receiving maximum-tolerated medications were treated with latanoprost additive therapy on a compassionate basis. MAIN OUTCOME MEASURES: Follow-up was up to 22 months with a mean of 13.9 +/- 5.7 months. Kaplan-Meier survival analysis with Mantel-Cox log-rank test was performed to determine the overall success of latanoprost additive therapy and to compare the success rates of high-dose pilocarpine, low-dose pilocarpine, and no pilocarpine therapies. The criterion for success was avoiding glaucoma surgery with IOP decrease of 20% or greater and final IOP less than 22 mmHg. The IOP change and its significance for patients satisfying and failing the criterion for success also were determined to assess the latanoprost additive therapy. In addition, a number of pretreatment variables, including pilocarpine therapy, were analyzed for a significant effect on the efficacy of latanoprost additive therapy using Cox proportional hazards regression analysis. RESULTS: Latanoprost additive therapy significantly lowered mean IOP by 3.9 +/- 5.5 mmHg at 3 months and by 3.5 +/- 5.8 mmHg at 12 months. The cumulative success rate of the latanoprost additive therapy was 70% at 1 month, 42% at 3 months, 40% at 6 months, and 30% at 12 months. Of the variables studied, only increased number of previous incisional glaucoma surgeries and IOP greater than 24 mmHg before latanoprost additive therapy were significant prognostic factors for failure of latanoprost additive therapy. Pilocarpine therapy in any dose had no significant effect. CONCLUSION: This study supports a trial of latanoprost additive therapy before glaucoma surgery in patients with IOP out of control while receiving maximum-tolerated medications irrespective of pilocarpine therapy and the pilocarpine dosage, especially when the number of previous incisional glaucoma surgery is less than three and the IOP is less than 25 mmHg.

Adult

Efficacy of apraclonidine 1% versus pilocarpine 4% for prophylaxis of intraocular pressure spike after argon laser trabeculoplasty.

OBJECTIVE: The authors compared the efficacy of apraclonidine 1% versus pilocarpine 4% prophylaxis of post-argon laser trabeculoplasty (ALT) intraocular pressure (IOP) spike. DESIGN: Prospective randomized clinical trial. PARTICIPANTS: Two hundred twenty-eight eyes of 228 patients with primary open-angle glaucoma undergoing ALT were studied. INTERVENTION: Patients were given 1 drop of either apraclonidine 1% (n = 114) or pilocarpine 4% (n = 114) 15 minutes before ALT. MAIN OUTCOME MEASURES: Peri-ALT IOPs and incidences of post-ALT IOP spikes at 5 minutes, 1 hour, and 24 hours were compared between the two groups. RESULTS: The two groups were similar in age, race, and medical dependency. Post-ALT mean IOPs at 5 minutes, 1 hour, and 24 hours were significantly lower than pre-ALT mean IOPs in both apraclonidine (P < 0.001) and pilocarpine (P < 0.001) groups. Incidences of IOP spikes greater than 1, 3, and 5 mmHg at 1 hour post-ALT were 21.1%, 14.9%, and 8.8% for the apraclonidine group and 12.3%, 5.3%, and 4.4% for the pilocarpine group (P = 0.076, 0.015, and 0.18 chi-square test). In the apraclonidine prophylaxis group, patients on long-term apraclonidine showed significantly higher incidence of post-ALT IOP spike than the patients without such long-term apraclonidine use (35.7%, 15 of 42 eyes, vs. 12.5%, 9 of 72 eyes; P = 0.003). In addition, peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy but without statistical significance (17.4%, 8 of 46 eyes, vs. 9.4%, 6 of 64 eyes; P = 0.17). CONCLUSION: Peri-ALT pilocarpine 4% was at least as effective as, if not more effective than, apraclonidine 1% in post-ALT IOP spike prophylaxis. Peri-ALT apraclonidine prophylaxis was not effective in patients on long-term apraclonidine, and peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy. Pilocarpine 4% can be considered as a first-choice drug for post-ALT IOP spike prophylaxis, especially in patients under treatment with apraclonidine.

Aged

Lessons learned from loosening of the McKee-Farrar metal-on-metal total hip replacement.

Clinical and radiographic data for 15 McKee-Farrar hip replacements that had failed because of aseptic loosening (4 stem loosening, 9 cup loosening, and 2 loosening of both components) between 0.6 and 21 years (average, 8.3 years) were compared with 15 hips in which the McKee-Farrar total hip replacement has survived between 21 and 26 years. Hips that loosened were biomechanically disadvantaged compared with those that demonstrated long-term survival. Radiographic evaluation demonstrated that in hips that were revised for aseptic femoral loosening, the offset was decreased by a mean of 1.4, whereas it was increased by a mean of 4.9 mm in the surviving hips (P = .04). Further, in hips revised for aseptic loosening, the center of rotation was medialized by a mean of only 1.4 mm, whereas the center of rotation was medialized by a mean of 6.4 mm in the surviving hips (P = .1). Unfavorable biomechanics results in increased joint reaction forces that could contribute to loosening of these prostheses. Five of 6 McKee-Farrar stems revised for aseptic loosening compared with 7 of 15 surviving stems were in varus (P = .1) and, as a result, had cement mantle defects in zones III and VII. Thus, in the McKee-Farrar, similar to what has been seen in hips with metal-on-plastic bearings, curved stems are associated with varus positioning, cement mantle defects, and loosening. Wear of the metal-on-metal articulation does not appear to be the cause of failure in these cases. Wear could not be detected radiographically. At revision surgery, there was no indication of excessive bearing wear or gross metal staining of periprosthetic tissues. Microscopic analysis of tissue sections demonstrated both metal and polymethylmethacrylate particles of variable size and shape. The variability of the particles suggests that they are likely the result of loosening and that they were not generated by bearing surface wear that could cause loosening. Although it is hoped that improvements in the wear resistance of the bearing will increase survivorship, this experience and analysis of the McKee-Farrar total hip replacement illustrates the importance of the implant design, biomechanics of the reconstruction, and role of surgical implantation technique.

Arthroplasty, Replacement, Knee

Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense.

In mammals, the Rho family GTPase Rac2 is restricted in expression to hematopoietic cells, where it is coexpressed with Rac1. Rac2-deficient mice were created to define the physiological requirement for two near-identical Rac proteins in hematopoietic cells. rac2-/- neutrophils displayed significant defects in chemotaxis, in shear-dependent L-selectin-mediated capture on the endothelial substrate Glycam-1, and in both F-actin generation and p38 and, unexpectedly, p42/p44 MAP kinase activation induced by chemoattractants. Superoxide production by rac2-/- bone marrow neutrophils was significantly reduced compared to wild type, but it was normal in activated peritoneal exudate neutrophils. These defects were reflected in vivo by baseline neutrophilia, reduced inflammatory peritoneal exudate formation, and increased mortality when challenged with Aspergillus fumigatus. Rac2 is an essential regulator of multiple specialized neutrophil functions.

Actins

Acupressure-acupuncture antiemetic prophylaxis in children undergoing tonsillectomy.

BACKGROUND: Acupuncture or acupressure at the Nei-Guan (P.6) point on the wrist produces antiemetic effects in awake but not anesthetized patients. The authors studied whether a combined approach using preoperative acupressure and intra- and postoperative acupuncture can prevent emesis following tonsillectomy in children. METHODS: Patients 2-12 yr of age were randomly assigned to study or placebo groups. Two Acubands with (study) and two without (placebo) spherical beads were applied bilaterally on the P.6 points; non-bead- and bead-containing Acubands, respectively, were applied on the sham points. All Acubands were applied before any drug administration. After anesthetic induction, acupuncture needles were substituted for the beads and remained in situ until the next day. All points were covered with opaque tape to prevent study group identification. A uniform anesthetic technique was used; postoperative pain was managed initially with morphine and later with acetaminophen and codeine. Emesis, defined as retching or vomiting, was assessed postoperatively. Ondansetron was administered only after two emetic episodes at least 2 min apart. Droperidol was added if emesis persisted. RESULTS: One hundred patients were enrolled in the study. There were no differences in age, weight, follow-up duration, or perioperative opioid administration between groups. Retching occurred in 26% of the study patients and in 28% of the placebo patients; 51 and 55%, respectively, vomited; and 60 and 59%, respectively, did either. There were no significant differences between the groups. Redness occurred in 8.5% of acupuncture sites. CONCLUSION: Perioperative acupressure and acupuncture did not diminish emesis in children following tonsillectomy.

Acupressure

Potentiation of cholecystokinin and secretin-induced pancreatic exocrine secretion by endogenous insulin in humans.

To investigate the effects of endogenous insulin on pancreatic exocrine secretion in humans, we evaluated the pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct in 21 healthy subjects (14 men and seven women). Samples of pancreatic juices were collected after intravenous injection of either glucose (50%, 40 ml), secretin (0.25 CU/kg), and cholecystokinin-8 (CCK) (40 ng/kg), or a combination of glucose, secretin, and CCK in six 5-min periods. The responses of plasma glucose, insulin, and C-peptide to intravenous administration of glucose were measured. After infusion of glucose, the plasma insulin and C-peptide levels were significantly increased and remained at high levels during 30-min experiments, intravenous administration of secretin and CCK resulted in significant increases of pancreatic secretion including volume, bicarbonate, and protein output. When glucose was simultaneously administered with secretin and CCK, pancreatic secretion was significantly increased, more than the effects achieved by the secretin and CCK. However, glucose alone did not increase basal pancreatic secretion. These observations suggest that endogenous insulin intensifies pancreatic secretion stimulated by secretin and CCK in humans.

Adult

Use of molecular subtyping to document long-term persistence of Corynebacterium diphtheriae in South Dakota.

Enhanced surveillance of patients with upper respiratory symptoms in a Northern Plains community revealed that approximately 4% of them were infected by toxigenic Corynebacterium diphtheriae of both mitis and gravis biotypes, showing that the organism is still circulating in the United States. Toxigenic C. diphtheriae was isolated from five members of four households. Four molecular subtyping methods-ribotyping, multilocus enzyme electrophoresis (MEE), random amplified polymorphic DNA (RAPD), and single-strand conformation polymorphism-were used to molecularly characterize these strains and compare them to 17 archival South Dakota strains dating back to 1973 through 1983 and to 5 isolates collected from residents of diverse regions of the United States. Ribotyping and RAPD clearly demonstrated the household transmission of isolates and provided precise information on the circulation of several distinct strains within three households. By MEE, most recent and archival South Dakota strains were identified as closely related and clustered within the newly identified ET (electrophoretic type) 215 complex. Furthermore, three recent South Dakota isolates and eight archival South Dakota isolates were indistinguishable by both ribotyping and RAPD. All of these molecular methods showed that recent South Dakota isolates and archival South Dakota isolates were more closely related to each other than to the C. diphtheriae strains isolated in other parts of the United States or worldwide. The data also supported the improbability of importation of C. diphtheriae into this area and rather strongly suggest the long-term persistence of the organism in this region.

Bacterial Typing Techniques

Regional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume.

The regional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the lung volume at which the boluses are delivered. To evaluate the effect of end-inspiratory lung volume on aerosol bolus delivery, we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5-microm mass median aerodynamic diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at lung volumes of 50, 70, and 85% of total lung capacity (TLC) end inhalation. By gamma camera analysis, we found significantly greater deposition in the left (L) vs. right (R) lungs at the 70 and 85% TLC end inhalation; ratio of deposition in L to R lung, normalized to L-to-R ratio of lung volume (mean L/R), was 1.60 +/- 0.45 (SD) and 1. 96 +/- 0.72, respectively (P < 0.001 for comparison to 1.0) for posterior images. However, at 50% TLC, L/R was 1.23 +/- 0.37, not significantly different from 1.0. These data suggest that the L and R lungs may be expanding nonuniformly at higher lung volumes. On the other hand, subsequent retention of deposited particles at 2 and 24 h postdeposition was independent of L/R at the various lung volumes. Thus asymmetric bolus ventilation for these very shallow boluses does not lead to significant increases in peripheral alveolar deposition. These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.

Adult

Photomovement of the gliding cyanobacterium Synechocystis sp. PCC 6803.

Using a computerized videomicroscope motion analysis system, we investigated the photomovements of two Synechocystis sp. (PCC 6803 and ATCC 27184). Synechocystis sp. PCC 6803 displays a relatively slow gliding motion. The phototactic and photokinetic speeds of this cyanobacterium in liquid media were 5 microns/min and 15.8 microns/min, respectively, at 3 mumol/m2/s of stimulant white light. Synechocystis sp. PCC 6803 senses light direction rather than intensity for phototaxis. Synechocystis sp. ATCC 27184 showed a weak photokinesis but no phototaxis. Analysis of Synechocystis sp. ATCC 27184 suggests that the loss of phototaxis results from spontaneous mutation during several years of subculture. When directional irradiation was applied, the cell population of Synechocystis sp. PCC 6803 began to deviate from random movement and reached maximum orientation at 5 min after the onset of stimulant white light. Synechocystis sp. PCC 6803 showed high sensitivity to the stimulant white light of fluence rates as low as 0.002 mumol/m2/s. Neither 1,3-dichlorophenyldimethyl urea nor cyanide affected phototactic orientation, whereas cyanide inhibited gliding speed. This result suggests that the phototaxis of Synechocystis sp. PCC 6803 is independent of photosynthetic phosphorylation and that its gliding movement is primarily powered by oxidative phosphorylation. In the visible wavelength region, 560 nm, 660 nm and even 760 nm caused positive phototaxis. However, 360 nm light induced strikingly negative phototaxis. Therefore, at least two independent photoreceptors may exist to control phototaxis. The photoreceptor for positive phototaxis appears likely to be a phytochrome-like tetrapyrrole rather than chlorophyll a.

Agar