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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 1,603 records · Page 89Linked to original sources

Binding characteristics of drugs to synthetic levodopa melanin.

To define binding characteristics of drugs, levodopa melanin was prepared with the aid of mushroom tyrosinase. The binding of radiolabeled substances was studied with increasing concentrations of melanin in a fixed volume of potassium phosphate buffer (pH 7.4) at 37 degrees. The affinity and capacity of the drug binding were calculated according to Langmuir's adsorption isotherm. The affinity constant of various sympathomimetic amines such as (-)-amphetamine, (+)-amphetamine, (-)-ephedrine, (+/-)-octopamine, and (+)-norepinephrine ranged from 1.1 to 2.8 X 10(5) M-1. The binding capacity for the amines ranged from 1.4 to 3.2 X 10(-9) mole/mg. Although the capacity of (+/-)-cocaine for binding was similar to that of the amines, the affinity was slightly higher, 8.9 X 10(5) M-1. The binding of atropine to the synthetic melanin appeared to be a saturable process with the affinity and capacity values of 0.2 X 10(5) M-1 and 7.6 X 10(-9) mole/mg, respectively. Although the binding lacks stereoselectivity, the drugs vary in their capacity and affinity to bind with melanin. The observed differential pharmacological and toxicologic properties of drugs in the pigmented tissues may in part be related to their differential bi binding characteristics.

Adsorption↗

Specialized transduction of colicin E1 DNA in Escherichia coli K-12.

Genetic studies were made on E. coli K-12 TM96, which carries recombinant molecules constructed by in vitro combination of colicin E1 DNA and a DNA fragment of E. coli for guanine synthesis derived from transducing phage. The recombinant molecules existed as stable plasmids within the cell and contained genes for colicin E1 immunity and the guaA enzyme (xanthosine 5'-monophosphate aminase) together with a part of the lambda genome, R through J: (R-A-F-J)+. A block of the lambda genome, int through Q, was not detected in the recombinant molecule. Thus, this recombinant molecule was named ColEl-coslambda-guaA, and the specialized tranduction of the ColEl-coslambda-guA DNA into various E. coli K-12 cells by lambda phage was described. Lysates prepared by lytic infection of lambda phage onto TM96 or by induction of TM96(lambda) lysogens contained transducing particles which could transduce gua-deleted E. coli to stable guaA+ cells. These transductants were proved to have similar genetic properties as those of TM96. The frequency of transduction was not affected by the presence of an attachement site for lambda, prophage lambda, colicin E1 plasmids, or the recA property within gua-deleted recipient cells. Transducing particles were resistant to EDTA treatment and most of them had an average density of about 1.472. This value corresponds to that of lambda phage particles, which contain about 72% of the lenght of lambda DNA.

Colicins↗

Thermodynamic characteristics of the adsorption of sulfanilamide, phenol, and n-butanol on bio-gel beads.

The thermodynamic properties of the adsorption of sulfanilamide, phenol and n-butanol on Bio-Gel beads have been studied. Bio-Gel was chosen as the adsorbent as it possesses both hydrophobic and hydrophilic sites on its surface. Adsorption of the former two adsorbates was found to be exothermic, and the relevant thermodynamic parameters at 20 degrees are in the ranges: deltaH degrees = -2.7 to -5.4 kcal/mole; deltaF degrees = -6.0 to -7.6 kcal/mole; deltaS degrees = +7.7 to +11.6 e.u. In the presence of urea, adsorption of sulfanilamide and phenol was partially disrupted. This, together with the large entropy gain of the process, indicates that both hydrogen bonding and hydrophobic bonding contribute cooperatively to the adsorption. On the contrary, adsorption of n-butanol, which was not susceptible to urea, was an endothermic process with the parameters, deltaH degrees = +5.8kcal/mole, deltaF degrees = -1.8 kcal/mole, and deltaS = +26.1 E.U. at 20 degrees. These data conform to the thermodynamic properties of hydrophobic bond formation. Finally, possible implications of these data in the structural assembly of lipoprotein molecules are discussed.

Adsorption↗

Additional evidence for hydrophobic bond formation in the adsorption of sulfanilamide on bio-gel beads.

We have previously suggested the involvement of both hydrogen binding and hydrophobic bonding in the adsorption of sulfanilamide on Bio-Gel beads. In the present study, we closely examined the concentration dependence of the binding curve and our proposed binding model has been corroborated. For comparison, binding parameters and thermodynamic data pertaining to the sulfanilamide-Sephadex system have been also evaluated.

Adsorption↗

The complement system in tumor immunity: significance of elevated levels of complement in tumor bearing hosts.

The elevation of complement level in the sera and depressed state of tuberculin reaction were observed in lung cancer patients. A clinical follow-up study demonstrated negative conversion of tuberculin reaction while keeping the complement at an elevated level during the observation period. This phenomenon can be explained; the complement system is elevated to compensate the depressed cell-mediated system to prevent the immunological surveillance system from invading agents in tumor bearing hosts. The immunological states of the patients with various diseases are classified into six stages according to the tuberculin reactivity, positive or negative, and complement level: elevated, normal, or depressed. A healthy control group is composed of the group of complement normal and tuberculin positive (Stage I). Most of acute inflammation falls into the elevated level of both complement and positive tuberculin reaction (Stage II). Sarcoidosis, leprosy, and Wegener's granulomatosis are divided into the elevated level of complement and depressed tuberculin reaction (Stage III). Systemic lupus erythematosus is in Stage V with the depressed state of both tuberculin reaction and complement level. A follow-up study of lung cancer patients showed a possible chronological sequence starting from Stage I through III, and finally to V, similar to the progression-of-disease process. The biological and medical significance related to the phenomenon is discussed, standing upon immunochemical, phylogenical, and immunogenetical standpoints of complement research.

Animals↗

Reflex swallowing elicited by water and chemical substances applied in the oral cavity, pharynx, and larynx of the rabbit.

Water and various chemical solutions were applied to the oral cavity, pharynx, and larynx of anesthetized rabbits to study their effects on the swallowing reflex. Laryngeal stimulation: Water was an effective stimulus in eliciting reflex swallowing; NaCL depressed this reflex. The effect of salt solutions on swallowing was dependent on anion species. Weakly hydrated anions had a depressing effect while greatly hydrated anions had a facilitating effect. The order of the depressing effect of the anions was Br-greater than SCN- greater than CL- congruent to NO3 -, and the order of the facilitating effect of anions was citrate greater than SO42 - greater than HCO3-. Oral and pharyngeal stimulation: Water elicited swallowing; however, this effect was less marked than that in the larynx. NaCL in concentrations lower than 200 mM had a depressing effect while at higher concentration it had a facilitating effect. Sucrose, acetic acid, and alcohol evoked successive swallowing in the first two or three trials. It was found that water applied to the laryngeal region had the marked effect of eliciting reflex swallowing and that most gustatory substances infused into the oral and pharyngeal regions had a facilitating effect on the initation of swallowing.

Acetates↗

Iris pigmentation and atropine mydriasis.

The experiments were designed to study the well-known pigment-dependent mydriatic effect of atropine in the eye. In vitro, relative to the accumulation of 3H-atropine by the nonpigmented rabbit iris, the pigmented iris accumulated high amounts of the drug. A nonpigmented tissue, stomch fundus strip, obtained from either albino or nonalbino animals, accumulated relatively low amounts of 3H-atropine. On repeated washings, the accumulated drug from the nonpigmented tissues was rapidly lost, T 1/2 of 14 minutes, while that accumulated by the pigmented iris was retained much longer. Although in vitro aqueous humor from serum-atropinesterase positive rabbits rapidly degraded atropine, extracts from irides of the same type of rabbit gave a single peak radioactivity, with Rf identical to the authentic atropine sulfate. The accumulation of 3H-atropine by pigmented human iris or pigment epithelium was similar to that observed for the pigmented rabbit iris. pA2 values of atropine from nonpigmented iris and from fundus strips varied between 8.58 and 8.88 with slope values close to 1. The pA2 value of atropine in pigmented iris was 8.82; at higher concentrations, atropine was less effective compared to the nonpigmented iris. In the pigmented iris, the lesser effectiveness of the drug at high concentration could be explained on the basis of accumulation of the drug by the pigment cell and its constituents. Thus, the free concentration of the drug in the vicinity of the muscarinic receptor will fall. The lesser concentration will give weaker muscarinic blockade in the pigmented iris. On repeated washing, the atropine blockade of the nonpigmented iris could be easily washed out while that in the pigmented iris was retained. In vivo, the relative T 1/2 for the duration of atropine mydriasis in rabbits were: albino atropinesterase-positive, 3.8 hours; nonalbino atropinesterase-positive, 12.4 hours; albino atropinesterase-negative is greater than or equal to 96 hours. Only the latter T 1/2 for the duration of atropine mydriasis is quite clear. The small magnitude of the mydriatic effect in humans is explained by the loss of free drug to the pigment cells and their constituents. The longer duration of mydriatic effect in the heavily pigmented eye is explained on the basis of slow release of the accumulated drug onto the muscarinic receptor.

Animals↗

Cinemicrographic analysis of the movement of flagellated bacteria. II. The ratio of the propulsive velocity to the frequency of the wave propagation along flagellar tail.

We took cinemicrographs of the movement of the flagellar tail of the peritrichously flagellated bacterium, Salmonella, swimming in a medium containing methylcellulose under a dark-ground microscope. By analysing the film, the velocity of translation u, the frequency of the propagation of helical waves along the tail fF and the frequency of the induced rotation of bacterial body fB of individual organism were measured and the experimental values of the ratios u/fF, u/fB and fF/fB were obtained. On the other hand, the theoretical values of these ratios were calculated by inserting the geometrical parameters describing the shapes and the sizes of the body and the tail of individual organism into the equations previously derived for the hydrodynamic model of the propulsion of flagellated bacteria (Holwill and Burge, 1963; Chwang and Wu, 1971). For four bacterial specimens presently analysed, the experimental values of u/fF ranged from 0.5 to 0.9, whereas the theoretical values were about 0.3. As reported by the preceding paper, such a tendency for the experimental values to exceed the theoretical ones by two or three times was also seen in u/fB and, consequently, the experimental and the theoretical values of fF/fB showed good agreement. From the results of these quantitative analyses of the movements of flagellated bacteria, it was concluded that the validity of the hydrodynamic model was further supported experimentally.

Cell Movement↗