PubMed Health⌕ Search

Biomedical subjects

W H Ko

Publications and source records attributed to W H Ko.

13 recordsLinked to original sources
PubMed1992

Modulation of trichosanthin antigenicity by coupling to dextran.

Trichosanthin (TCS) is a plant-derived type I ribosome-inactivating protein with a wide spectrum of biological and pharmacological activities. Recently, it was covalently coupled to dextran in order to prolong its half-life in plasma. The major biological activities were generally retained but at lower potency. The immunogenicity of the dextran-trichosanthin (DX-TCS) was compared to that of TCS itself in this study. The results showed that mice immunized with TCS produced 8 times as much TCS-reactive IgE than those immunized with DX-TCS. However, both TCS and DX-TCS immunization produced similar titers of TCS-reactive IgG. A trace of dextran-reactive IgG was detected in mice immunized with DX-TCS. Thus, coupling of TCS to dextran reduced its antigenicity but slightly enhanced that of dextran, and the conjugate elicited less IgE than TCS.

Adjuvants, Immunologic↗
PubMed1992

Effect of lysine on hemolysis-induced kidney damage.

The mechanism of kidney damage commonly seen in patients with intravascular hemolysis is not entirely clear. Injection of distilled water (4 ml within 5 seconds) into the carotid arteries of rats resulted in intravascular hemolysis leading to hemoglobinemia, hemoglobinuria, reduction in inulin clearance, and elevation of urine N-acetyl-beta-D-glucosaminidase (NAG) excretion. When the same experiment was repeated with simultaneous infusion of the positively charged amino acid lysine (30 mmol/L at 3.4 ml/hour), the inulin clearance was unchanged. Urinary NAG excretion was elevated but significantly lower than that in similar rats without lysine infusion. This suggested that lysine protected the kidney from the deleterious effect of hemolysis. Such protection was not observed when the neutral amino acid glycine was infused. Because positively charged but not neutral amino acids are known to inhibit renal protein reabsorption, the protective effect of lysine could be due to inhibition of hemoglobin reabsorption, which might be an important step in the pathogenesis of kidney damage.

Acetylglucosaminidase↗
PubMed1991

Increasing the plasma half-life of trichosanthin by coupling to dextran.

Trichosanthin (TCS) is a plant protein which has a wide spectrum of pharmacological activities. It was demonstrated recently that this compound suppressed the replication of human immunodeficiency virus (HIV-1) in vitro. The mechanism of action is believed to be inhibition of protein synthesis. Trichosanthin is a low molecular weight protein which is expected to be easily filtered and eliminated through the kidney. To minimize renal loss, the molecular size of trichosanthin can be increased by coupling to dextran. The larger complex will not undergo glomerular filtration and therefore renal loss can be prevented. This study investigates the kidney's role in trichosanthin elimination and the beneficial effect afforded by coupling to dextran in prolonging plasma half-life. For this purpose, a radioimmunoassay has been developed to determine the concentration of TCS in plasma and urine. The sensitivity of this assay is in the nanogram range. Trichosanthin was coupled to dextran T40 by a dialdehyde method and successful coupling was confirmed by gel filtration chromatography. The complex retained specific binding to trichosanthin antibodies with decreased affinity which can be partially reversed after incubation with dextranase; an enzyme that digested dextran. The pharmacokinetics of intravenously administered trichosanthin (0.75 mg/kg) was compared between two groups of rats with normal and impaired renal function (bilateral renal arterial ligation). Rats with ligation showed a decrease in plasma clearance from 4780 +/- 570 to 220 +/- 20 microL/min and an increase in the mean residence time from 9 +/- 1 to 145 +/- 16 min. Despite the several-fold difference in these parameters, recovery of trichosanthin from normal rat urine was only 0.38 +/- 0.05%. This value can be increased by using higher injection doses. The data indicate that the kidney is an important organ for the elimination of trichosanthin. When the dextran-trichosanthin complex was injected into normal rats trichosanthin activity was not detected in the urine. All the pharmacokinetic parameters suggest that the dextran-trichosanthin complex stayed longer in the body and maintained a much higher plasma concentration than trichosanthin.

Animals↗
PubMed1988

Ventricular volume regulation: a mathematical model and computer simulation.

A mathematical model of ventricular volume regulation based on fluid mechanical principles has been constructed using a systems engineering approach. The parameters used in the model are based on clinical observation, laboratory investigation, and presumptions that will be tested later. The model was constructed to be the basis of a computer simulation. Using the computer simulation, information obtained from the literature and laboratory hypotheses regarding pathophysiology, several enigmatic conditions were tested. The model predicted that over-production of cerebrospinal fluid, as in the case of choroid plexus papilloma, could by itself lead to distention of the ventricular system. In simulating pseudotumor cerebri, if cerebrospinal fluid absorption at the arachnoid villi is impaired and the brain itself is rendered incompressible by swelling, intracranial pressure rises and ventricular volume diminishes. Conversely, in normal-pressure hydrocephalus, if cerebrospinal fluid flow is restricted between the spinal and cortical subarachnoid spaces and the brain is made more compressible, the ventricular volume increases with minimal increases in intracranial pressure. This mathematical model and its associated computer simulation is useful in predicting the behavior of the volume of the cerebral ventricles to a variety of pathological phenomena.

Animals↗
PubMedDate not supplied

Electromagnetic implantable middle ear hearing device of the ossicular-stimulating type: principles, designs, and experiments.

This report analyzes the principles, describes designs, and discusses the advantages and disadvantages of different types of implantable middle ear hearing devices. Preliminary acute experiments using an electromagnetic transducer for an implantable hearing device of the ossicular-stimulating type were performed in cats. A miniature samarium cobalt rare earth magnet was cemented on the head of the stapes. An electromagnetic coil powered either by direct wiring or by telemetry was used to stimulate the stapes. The performance of the system was evaluated by electrophysiologic assessment of hearing (brain stem evoked response potentials). The findings showed that the device is functional with good "implant gain" (35 dB average) and consumes reasonably low current (0.6 mA) with telemetry. Further investigation is necessary in order to develop an implantable middle ear hearing device with successful clinical application.

Animals↗