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Biomedical subjects

J R Lin

Publications and source records attributed to J R Lin.

At least 19 recordsLinked to original sources

Development of a novel aspherical mirror bender for an active grating.

A novel monolithic mechanical bender has been designed and fabricated to meet the requirements of an active polynomial grating in a new soft X-ray scattering and emission beamline at the National Synchrotron Radiation Research Center, Taiwan. This compact bender achieves nearly fixed center point under different bending conditions. Moreover, the compact bender can be bent to a desirable third-order polynomial surface profile to cancel the defocus and coma aberrations using two PZT actuators. Theoretical analysis reveals that the grating has unprecedented spectral resolving power. A detailed mechanical analysis has been conducted and a prototype bender was fabricated and tested. The results indicate that the performance of the bender is excellent and is therefore suitable to be used in the active grating.

Computer-Aided Design↗

Gating kinetics of potassium channel and effects of nerve growth factors in PC12 cells analyzed with fractal model.

AIM: To study the gating kinetics of voltage-dependent K+ channels i n clonal pheochromocytoma (PC12) cells and the effect of nerve growth factor (NGF) on it. METHODS: Outward currents of K+ channel were recorded in PC12 cells cultured with or without NGF using cell-attached patch-clamp technique. The kinetic features of K+ channel and the effect of NGF on them were analyzed based on t he fractal model. RESULTS: The fractal dimension D for the closed durations of K+ channel in PC12 cells cultured without NGF was proportional to the absolute value of the pipette potential (Vp). Whereas the fractal dimension D' was inversely proportional to it. Under pipette potentials of 0, -30, -50, and -70 mV, the values of D were 1.75, 1.88, 1.95, and 2; and of D' were 1.51, 1.40, 1.34, and 1.23. After the addition of NGF the changes in the fractal dimensions became more complex. At the same pipette potential, fractal dimensions for K+ channel in PC12 cells cultured with NGF for both the open and closed durations were not greater than those in PC12 cells cultured without NGF. The kinetic setpoints for both the close and open durations did not vary with the pipette potential with values as follows: A (without NGF) = 0.29 +\ -0.05, A(with NGF) = 0.71 +\- 0.06, A' without NGF) = 0.110 +\- 0.020, and A' (with NGF) = 0.38 +\- 0.08. CONCLUSION: The voltage dependence of D (without NGF) increases the probability of the channel for remaining closed for long durations as the patch is depolarized, and that of D' (without NGF) decreases the probability of the channel for remaining open for long durations as the patch is depolarized. The addition of NG F in the PC12 cell culture accelerates the dynamic process of the K+ channel occurring over long time scales.

Animals↗

[Ion single channel signal restoration and parameters' estimation based on the hidden Markov models].

The single ion channel signal is stochastic ionic current on the order of 1 pA recorded by patch clamp. Because the weakness of the signal, the background noise always dominates in the recordings, the threshold detector traditionally used in patch clamp to denoise and restore the channel signal can't work satisfactorily. This problem was analyzed mathematically, and a signal restoring and parameters estimating scheme called HMM algorithm was studied. The algorithm has been validated by simulation and the results suggest it performs effectively in the situation of low signal to noise ratio where the threshold detector fails completely.

Algorithms↗

[The development of event related-potential acquisiting system].

A system for acquisiting event-related-potential signalsis presented, making use of random-sequences visial symbols. ATMEL AT89C51 controls Max 186 serial conversion and interface Max202 to serially send data to host computer for poct processing.

Analog-Digital Conversion↗

Normocalcemic effect of gallium nitrate in a hypercalcemic rat model.

An established rat hypercalcemia model was used to study the effects of gallium nitrate on elevated serum calcium levels. Gallium nitrate was administered by i.v. or i.p. injection at daily doses of 0.07-0.45 mmol/kg for 5 days to the hypercalcemic rats beginning 1 day following surgery. A dose-correlated normocalcemic response was observed. Gallium nitrate administered late after the induction of the hypercalcemic state was also effective in reducing serum calcium levels. The p.o. administration, however, even at doses as high as 0.45 mmol/kg, did not reduce serum calcium to normal levels. The values of area under the concentration versus time curve (0-24 h) of gallium in normal rats were comparable after i.v. [49.2 (micrograms/ml)h] or i.p. [57.0 (micrograms/ml)h] injections. In contrast, the p.o. route achieved only 15% bioavailability, which may explain the ineffectiveness of p.o. administered gallium nitrate at that dose level. This study suggests that daily i.v. bolus injections of gallium nitrate for managing hypercalcemia may be potentially as effective as the current regimen of continuous i.v. infusion.

Administration, Oral↗

In vitro neutralization of the inhibitory effect of Microcystin-LR to protein phosphatase 2A by antibody against the toxin.

Microcystin-LR (MCYST-LR) was found to be a very potent protein-phosphatase 2A (PP2A) inhibitor at an ID50 as low as 0.1 nM. Comparing to calyculin A and okadaic acid, MCYST-LR was found to be about 100 times stronger than calyculin A and okadaic acid for their inhibition to PP2A. The inhibitory effect on PP2A by MCYST-LR was abolished when antibodies against MCYST-LR were present in the assay system. Polyclonal antibodies were more effective than monoclonal antibodies in reversing the inhibitory effect. A dose-dependent neutralization of the inhibitory effect of MCYST to PP2A by anti-MCYST polyclonal antibodies were observed. Almost 80% of the enzyme activity was restored when as low as 0.012 micrograms of Pab was present. The specific reaction caused by the antibody was evident from an analysis that the antibodies had no effect on reversing the inhibition of PP2A caused by okadaic acid and calyculin A.

Animals↗

Determination of peplomycin in mouse tissues and biofluids by radioimmunoassay.

Peplomycin, an antitumour antibiotic analogue of bleomycin, was measured in mouse tissues using a rapid radioimmunoassay. Antiserum, obtained by immunizing rabbits with peplomycin-bovine serum albumin conjugate, showed no significant cross-reactivity with the closely related peplomycin analogues bleomycin and liblomycin, nor with a number of other structurally unrelated antitumour drugs. The assay is sensitive and can detect peplomycin levels as low as 2 ng ml-1. The relative intra- and inter-assay standard deviation is < or = 5%, indicating good assay reproducibility. Peplomycin levels in mouse tissues were easily determined without extraction. Fifteen minutes after administration of a single intraperitoneal dose of peplomycin at 8.5 mg kg-1 (1/10 of LD50), high drug levels were found in plasma (46 micrograms ml-1), kidneys (38 micrograms g-1), urine and bladder (32 micrograms ml-1), followed by gastrointestinal tract (13 micrograms g-1), lung (8 micrograms g-1), spleen (3.7 micrograms g-1), heart (3.6 micrograms g-1), gall bladder (2.7 micrograms g-1), liver (2 micrograms g-1), and brain (0.6 microgram g-1). The total amount of drug in all these organs accounted for more than 80% of the dose administered. We conclude that the radioimmunoassay is sensitive and reproducible and is an ideal tool for measuring peplomycin in tissues and biofluids for pharmacological studies.

Animals↗

[The in vitro potentiation of LAK cell cytotoxicity in cancer and aids patients induced by F3--a fractionated extract of Astragalus membranaceus].

The in vitro induction of LAK cell activity was studied in cancer and AIDS patients. F3, an immuno-regulatory component of Astragalus membranaceus was shown capable of potentiating the LAK cell inducing activity of rIL-2. The killing activity against Hs294T melanoma cell line of LAK cells induced by 50 U/ml rIL-2 in the presence of F3 (55 micrograms/ml) reached 64% which was comparable to that (60%) induced by 500 u/ml of rIL-2 alone. With F3 plus rIL-2, the effector to target cell ratio could be reduced to one-half in order to obtain an equivalent level of cytotoxicity when rIL-2 was used alone. In some patients, whose peripheral blood lymphocytes were relatively inert to rIL-2, F3 could make them responsive to rIL-2. These results imply that F3 may be useful to potentiate LAK cell activity, reduce the amount of rIL-2 and thus minimize the later's toxic side effects when used in vivo.

AIDS-Related Complex↗

Depletion of patients' plasma tryptophan using tryptophan side-chain oxidase columns.

The use of the enzyme tryptophan side-chain oxidase, isolated from Pseudomonas XA, was explored in 3 patients with refractory acute lymphocytic leukemia. Patients were given either a low-tryptophan diet or tryptophan-free hyperalimentation, prior to and during therapy. Their plasma, separated by pheresis, was continuously passed through a tryptophan depletion column containing the immobilized tryptophan side-chain oxidase. Up to 4 plasma volumes were passed through the column daily, 5 days per week for 2-3 weeks, and plasma tryptophan levels, both free and total, were measured by high-performance liquid chromatography. Pre- and postcolumn plasma samples were collected throughout the pheresis procedure. All postcolumn plasma samples had unmeasurable tryptophan levels throughout the treatment period, whereas precolumn samples were always measurable. Generally, tryptophan levels of plasma isolated from peripheral blood decreased after therapy, but rebounded by the next day. The enzyme depletion column reduces circulating plasma tryptophan levels, and its use is well tolerated by patients. However, further development of this method will require study of the effects of diet and of the duration, interval, and frequency of use of this column on therapeutic efficacy. Problems include difficulties with extended diet compliance and apparently intensive mobilization of tryptophan from body stores, which may preclude the clinical application of this enzyme depletion column.

Chromatography, High Pressure Liquid↗

[Oral complications following a herpes zoster infection of trigeminal nerve].

A case of herpes zoster involving the ophthalmic and maxillary divisions of the trigeminal nerve is reported. It presented as a oral herpes zoster infection with prodromal odontalgia and progressed to spontaneous exfoliation and devitalization of teeth and osteonecrosis of the maxilla. The literature is reviewed and the pathophysiology of tooth exfoliation, tooth devitalization and osteonecrosis by V-Z viruses are discussed in addition to the management of herpes zoster and post-zoster complications.

Adult↗

Determination of plicamycin in plasma by radioimmunoassay.

This article describes a method for the determination of plicamycin in plasma by radioimmunoassay. The anti-plicamycin antibody was produced against a plicamycin-bovine serum albumin conjugate prepared by using diazotized p-aminobenzoic acid as a cross-linker. The radiolabeled ligand, 125I-plicamycin, was prepared by the chloramine-T method. The linear plicamycin concentration range was 7-400 ng/ml. The coefficients of variation for intra- and interday variabilities were 7.5 and 15%, respectively. No interference was observed from either the structurally related chromomycin A or concomitantly used drugs hydroxyurea or allopurinol. With this method of testing, plicamycin levels in plasma could be determined in patients receiving small (0.85-1.0 mg/m2) therapeutic plicamycin doses. Preliminary pharmacokinetic data in humans indicate that the plasma drug disappearance curve was biphasic with a mean elimination half-life of 10.6 +/- 1.7 h, total clearance rate of 11.1 +/- 0.4 ml/min/m2, and area under the plasma drug concentration-time curve of 1,289-1,546 ng-h/ml. This assay method is clinically useful for pharmacokinetic studies of plicamycin and may be helpful in the design of rational therapeutic drug trials.

Antibody Specificity↗

Characterization of a monoclonal antibody which is an activator of rabbit platelets.

A monoclonal antibody (MAb) raised against rabbit platelet membranes was shown to be a strong agonist to induce platelet aggregation and secretion. This MAb, designated 19CB-1, was identified as an IgM and purified to near homogeneity by ammonium sulfate precipitation and Q-sepharose column chromatography. Aggregation induced by 19CB-1 was only slightly affected in the presence of creatine phosphate/creatine phosphokinase and aspirin, indicating that it was not mediated through the cyclooxygenase pathway and the release of ADP. 19CB-1 Fab fragments did not induce platelet aggregation. However, 19CB-1-induced aggregation was inhibited by these Fab fragments. 19CB-1 also elicited a rise in cytoplasmic calcium concentration in fura-2 loaded platelets. In the absence of external calcium, a substantial calcium signal remained to be observed, suggesting the release of calcium from intracellular stores in response to 19CB-1. This MAb reacted primarily with a polypeptide of Mr = 57,000, as revealed by immunoblotting. These results suggest that the 57 kDa antigen is one of the platelet surface proteins directly involved in the activation of rabbit platelets.

Adenosine Diphosphate↗

Liblomycin-mediated DNA cleavage in human head and neck squamous carcinoma cells and purified DNA.

Liblomycin (LBM), a novel bleomycin analogue, and bleomycin A2 (BLM A2) were compared with respect to their relative potential to inhibit growth in a human head and neck squamous carcinoma cell line and to produce DNA damage within cellular DNA and nuclei DNA and against isolated naked DNA. Against the BLM-sensitive cell line 183A, the concentration of LBM that inhibits cell growth by 50% was 1.1 microM for a 30-min drug exposure, while it was 23 microM for BLM A2. Drug-mediated DNA double-strand cleavage within cells was compared with the relative ability of these drugs to produce DNA cleavage in isolated 183A cell nuclei. Though 30-min exposures of cells to equimolar concentrations of both drugs resulted in 4-fold greater cellular DNA damage by LBM than BLM A2, the two drugs were nearly equipotent in producing DNA injury within isolated nuclei. Against Simian virus 40 DNA, however, LBM was 10-fold less effective than BLM A2 in producing Forms II and III DNA from Form I DNA. Radioactivity from either [3H]BLM A2 or 125I-LBM found associated with cells after a 30-min incubation period was also assessed in the 183A cell line. The exposure of cells to radiolabeled drug (1 microM) resulted in a 71-fold greater amount of cell-associated radioactivity for LBM than for BLM A2. The relative abilities of the 183A cell line to partially reseal LBM- or BLM A2-mediated DNA double-strand breaks were also assessed. No preferential repair of overall drug-mediated DNA injury, however, was observed. Finally, drug-mediated specific cleavage sites on pBR322 DNA were determined. At doses that gave the same extent of DNA cleavage, both BLM A2 and LBM gave similar patterns of strand scission, although minor differences were observed. Taken together, these data demonstrate that the greater efficacy of LBM against the BLM-sensitive head and neck squamous cell line is due mainly to LBM's greater association with cells over a defined time period, even though the DNA cleaving ability of LBM is relatively lower than that of BLM A2.

Base Sequence↗

Aortic and pulmonary input impedance in patients with cor pulmonale.

The hydraulic load of the right and left ventricles and the clinical effects of nifedipine were evaluated in 8 normal subjects (mean age: 55 years) and 8 patients with cor pulmonale secondary to chronic obstructive lung disease (mean age: 57 years). It was found that there were differences in the right ventricular resistance (174.62 +/- 25.96 vs 468.57 +/- 178.81 dyne/sec/cm-5), first zero crossing frequency (3.62 +/- 0.34 vs 6.07 +/- 3.56 Hz), steady power (218.95 +/- 32.25 vs 359.44 +/- 37.46 mW) and total power of right ventricle (275.81 +/- 36.18 vs 440.46 +/- 85.16 mW) between the normal and cor pulmonale patients, respectively. However, no significant changes in characteristic impedance, pulsatile power or aortic impedance were observed in the right pulmonary artery. After administration of nifedipine to patients with cor pulmonale, there were significant changes in resistance (468.57 +/- 178.81 vs 256.36 +/- 178.56 dyne/sec/cm-5), steady power (359.44 +/- 37.46 vs 225.51 +/- 114.64) and total power (440.46 +/- 85.16 vs. 289.27 +/- 50.85) of the pulmonary artery, respectively. Otherwise there were no significant changes in aortic input impedance or characteristic impedance of right pulmonary artery and pulsatile power. In conclusion, we found that: 1) the hydraulic vascular load in the right ventricle was higher in patients with cor pulmonale, 2) characteristic impedance that was not increased in cor pulmonale patients may be due to a dilated pulmonary artery, 3) there was no impedance mismatch between left ventricle and systemic arterial system in patients with cor pulmonale, and 4) by reducing the pulmonary vascular resistance through nifedipine administration, the total external right ventricular power might be reduced, without affecting the proximal pulmonary arterial compliance.

Aorta↗

Diagnosis and treatment of giant cell tumor in the thoracic spine.

A 23-year-old woman with incomplete paralysis was operated upon for a giant cell tumor in the thoracic spine. X-ray films revealed a destruction lesion in the vertebral body of the 12th thoracic vertebra. On the plain thoracic computed tomography scan, the finding was a soap-bubble appearance with a linear high density area in the mass lesion which destroyed the vertebral body. Preoperative angiography showed no apparent feeding artery to the tumor tissue; preoperative myelography showed incomplete block at the level of the 12th thoracic vertebra. A radical operation was carried out in one stage via a combined antero-posterior approach. In order to give radiotherapy immediately after operation, a vascular pedicled rib graft was made. This paper discusses the role of thoracic computed tomography scan in the diagnosis of giant cell tumor and the surgical techniques used in treatment.

Adult↗

[Immune restoration of local xenogeneic graft-versus-host reaction in cancer patients in vitro and reversal of cyclophosphamide-induced immune suppression in the rat in vivo by fractionated Astragalus membranaceus].

Through the process of fractionation, purification by gel filtration chromatography and thereafter the screening with an in vitro local xenogeneic graft-versus-host reaction (XGVHR) model, a fraction was identified as a potent immunorestorative agent and was designated "Fraction 3" (F3). Using the XGVHR in vitro as a model assay for T cell function again, F3 was studied on mononuclear cells (MNC) from 13 cancer patients and exhibited significant immunorestorative activity, with an increase in local XGVHR (compared to untreated cells) of 151.34 +/- 46.02 mm3 vs 57.80 +/- 16.44 mm3, P less than 0.001. The in vitro augmented immune reactions induced by F3 in cancer patients also significantly exceeded the local XGVHR observed in the untreated MNC derived from 9 normal donor controls (94.15 +/- 9.16 mm3, P less than 0.005). In a newly developed in vivo XGVHR animal model, pretreatment of rats with F3 resulted in a significant abrogation of the local XGVHR with a reversal of the immunosuppressive effect of cyclophosphamide from 99.42 +/- 9.2 mm3 (positive control) to 39.78 +/- 8.3 mm3 (P less than 0.001). This reversal was complete as the volume of the abrogated local XGVHR was comparable to that of the negative control (no cyclophosphamide-priming, saline injection only) 34.79 +/- 5.69 mm3 (P greater than 0.1). These results suggest that F3 retained the immunopotentiating activity of the original crude extract and form the rational basis for the use of Astragalus in immunotherapy.

Adjuvants, Immunologic↗