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Biomedical subjects

A Wada

Publications and source records attributed to A Wada.

At least 451 records · Page 25Linked to original sources

Dynamic light-scattering studies on thermal motions of native DNAs in solution.

The basic character of dynamic light-scattering properties of native DNA was investigated on two DNA samples. The degree of non-single exponentiality of photocount correlation functions, C(t), and its dependence on K are quantitatively characterized by two methods. The spectral linewidth, Ts, determined from C(t) exhibits a K dependence near to but significantly different from the prediction for Rouse-Zimm (RZ) chains by Dubois-Violette and De Gennes: It is inferred from data on lambda-DNA that the exponent in the K dependence of the spectral linewidth for native DNA takes a value larger than 3 in the K region corresponding to the 'K3' region for RZ chains. These results are in good agreement with the prediction from the dynamic theory of semiflexible chains presented by one of us (K.S.). The apparent diffusion coefficients are fairly insensitive to DNA concentration and ionic strength at large K. On the other hand, it is indicated that the stiffness of native DNA may vary with temperature even in a temperature range substantially lower than that of melting.

Bacteriocin Plasmids↗

Stability distribution in the phage lambda-DNA double helix: a correlation between physical and genetic structure.

Statistical analyses on the positional correlation of physical-stability and base-sequence distribution maps with genetic map are made for the whole DNA (48502 bases) of lambda-phage. The susceptibility to a double-helix unfolding perturbation and the fraction of the transient opening of a particular region of the double helix are adopted to define this physical stability. The principal features obtained are: A) The DNA double strand of protein coding regions is found to have homostabilizing propensity around a defined stability which is characteristic to each individual gene. B) The stability of the double helix in non-protein coding region fluctuates, on average over the whole region, more than that in protein coding region. C) Boundary regions of protein coding and non-protein coding regions are regions of high stability-fluctuation. Stability especially fluctuates at the protein-coding-region side of the boundary. Contrary to the quiet feature of the interior part of protein coding region rather noisy part exists at its edge. D) One frequently opening region coincides with the attaching site for the site specific recombination between phage and bacterial DNA. There are two possible ways to explain the noisy feature in the stability distribution in non-protein coding regions: 1) The region has been used as the locus of recombination as evolution took place. Thus DNAs which were homostabilized around a different value characteristic to each individual DNA, have been joined there many times, so that the noise has accumulated as a remnant of evolutional history; and/or 2) the base-composition homogenizing or double-helix homostabilizing mechanism does not work in unneeded region such as non-protein coding region or introns. Since corresponding characteristics have been found in our previous analyses on other viral and globin-gene DNAs, the rules mentioned above may be comprehensively extended to other DNAs.

Bacteriophage lambda↗

Angiotensin-converting enzyme activity is reduced in brain microvessels of spontaneously hypertensive rats.

Angiotensin -converting enzyme (ACE) activity in brain microvessels of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) controls was measured. Cerebral microvessels, prepared from the cerebral cortices by the albumin flotation and glass bead filtration technique, were free of neuronal and glial elements. ACE activity in brain microvessels of SHR was lower than that of WKY. A Woolf - Augustinsson -Hofstee plot showed that the reduction of the enzyme activity in SHR was due to a 30% decrease in Vmax, without any change in Km for substrate. The decrease of ACE activity in brain microvessels of SHR may indicate an impairment of the central renin-angiotensin system and may be related to cerebral microvascular dysfunctions occurring in hypertension.

Animals↗

Relationship between goblet cells and carcinoma of the pancreas during N-nitrosobis(2-hydroxypropyl)amine-induced carcinogenesis in Syrian golden hamsters.

During N-nitrosobis(2-hydroxypropyl)amine-induced pancreatic carcinogenesis in Syrian golden hamsters, both carcinoma and dysplasia could be distinctly classified into two types according to whether they did or did not contain goblet cells. Goblet cell-containing dysplasia developed mainly in the larger duct, and majority of goblet cell-containing carcinomas showed a pattern of papillary adenocarcinoma. It seems most probable that goblet cells are predysplastic and precancerous changes. On the other hand, dysplasia without goblet cells developed mainly in the smaller ductules, and a majority of carcinomas without goblet cells showed a pattern of poorly differentiated adenocarcinoma. These findings seem to correspond well with the relationship between human pancreatic cancer and mucus-secreting cells. The behavior of the goblet cells of hamster pancreatic ducts might be a good model for that of human mucus-secreting cells, especially mucous cells.

Animals↗

Effect of phospholipid on aldosterone biosynthesis by a cytochrome P-450(11) beta-reconstituted system.

Effect of phospholipid on aldosterone synthesis catalyzed by a cytochrome P-450(11)beta-reconstituted system was examined. Corticosterone was incubated with P-450(11)beta in the presence of phosphatidylcholine, phosphatidylethanolamine, cardiolipin, phosphatidylinositol, or phosphatidylserine. These phospholipids stimulated the rate of aldosterone- and 18-hydroxycorticosterone-synthesis, although the mode of stimulation by neutral phospholipids was different from that by acidic phospholipids. In the presence of a phospholipid mixture containing the lipids in the same molar ratios as found in adrenocortical mitochondria, the rate of production of aldosterone increased 10-fold over the rate without the lipids, and that of 18-hydroxycorticosterone increased 3-fold. The maximal synthetic rates of aldosterone and 18-hydroxycorticosterone were 2 and 5 nmol/nmol P-450/min, respectively.

18-Hydroxycorticosterone↗

Reconstitution mechanism of nucleosome core particles mediated by poly(L-glutamic acid).

Poly(L-glutamic acid) has been reported to mediate in vitro nucleosome assembly (Stein, A., Whitlock, J.P., Jr. and Bina, M. (1979) Proc. Natl. Acad. Sci. U.S.A. 76,5000-5004). To study the reaction mechanism, we have reconstituted nucleosome core particles from chicken erythrocyte core DNA and core histones in the presence of poly(L-glutamic acid) and analyzed the assembly products by polyacrylamide gel electrophoresis. Poly(L-glutamic acid), which binds and forms a large complex with core histones, is replaced with core DNA in the reconstitution process. When histone-poly(L-glutamic acid) complex and core DNA are mixed with a histone:DNA ratio of 1.0, the yield of core particles increases by prolonged reconstitution time. Two phases with a distinct time range appear in the process. In the fast phase within 30 min, 60% of the DNA is involved in products containing histones: reconstituted core particles, a larger nucleoprotein complex and aggregation. In the second phase, the remaining DNA and the DNA in the aggregation decrease, and the core particles increase slowly. The yield of core particles is approx. 60% after 24 h. The slow phase is not observed by reconstitution with a histone:DNA ratio of 2.0 in the initial mixture. The reaction scheme of the assembly process derived from these data is given. Based on the in vitro reaction scheme, the possible role of in vivo 'nucleosome assembly factors' is also discussed.

Animals↗

Correlation between thermal stability maps and genetic maps of double-stranded DNAs.

The positional correlation of boundaries of cooperatively melting regions with boundaries of protein coding regions and mere open reading frames, and with cleavage sites of restriction enzymes and S1 nuclease are statistically examined for phi X174, G4, fd, SV40, BKV, and polyoma DNAs. A statistically significant correlation does exist in the case of boundaries of protein coding regions, but none is detected for boundaries of mere open reading frames or cleavage sites of restriction enzymes and S1 nuclease. The significant correlation disappears when the cooperativity of melting of the DNA double strand decreases to a nonphysiological condition. The result presents the first evidence showing that a physical property of DNAs correlates with their biological function.

Base Composition↗

Carcinoid tumor of the gallbladder associated with adenocarcinoma.

A case of carcinoid tumor of the gallbladder associated with adenocarcinoma in a 56-year-old man is reported and a review of the literature is made. The tumor was a polypoid mass with a size of 5.5 X 4.0 X 2.8 cm. Histologically, the tumor showed carcinoid and adenocarcinoma with areas of mucous change. Tumor cells containing argyrophil granules were observed in both carcinoidal and adenocarcinomatous areas, but no argentaffin granules were detected in either of the neoplastic areas. Some of the tumor cells had both argyrophil granules and mucin in the same cytoplasm. The electron microscopic study revealed several tumor cells containing neurosecretory granules; however, no clinical signs of hormonal activities of the tumor were observed. The patient died of generalized bone metastases 16 months after surgery. This appears to be the second case of composite tumor of the gallbladder.

Adenocarcinoma, Mucinous↗

Suppression by phospholipase A2 inhibitors of secretion of catecholamines from isolated adrenal medullary cells by suppression of cellular calcium uptake.

The involvement of phospholipase A2 in the secretion of catecholamines and cellular uptake of 45Ca2+ was investigated in isolated bovine adrenal medullary cells. In these cells, stimulation of cholinergic receptors by carbamylcholine causes the activation of receptor-linked Ca-channels and influx of Ca2+ is known to trigger the secretory process. Phospholipase A2 inhibitors, such as quinacrine, chloroquine, quinine and p-bromophenacyl bromide, all inhibited the secretion of catecholamines evoked by carbamylcholine in a dose-dependent manner. These phospholipase A2 inhibitors also inhibited the cellular uptake of 45Ca2+ evoked by carbamylcholine with similar dose-response curves to those for inhibition of catecholamine secretion. The inhibition by phospholipase A2 inhibitors was found to be distinct from inhibition by d-tubocurarine which competitively blocks acetylcholine receptors, and from inhibition by diltiazem which acts as a Ca-antagonist at Ca-channels. Phospholipase A2 inhibitors seem to suppress the secretion of catecholamines by interfering with the linkage between acetylcholine receptors and Ca-channels by the membrane effects including the inhibition of endogenous phospholipase A2 activity of the adrenal medullary cells.

Acetophenones↗

Preference of oxygenation between alpha and beta subunits of haemoglobin. Results of multidimensional spectroscopic observation.

The distribution of oxygen between the subunits of haemoglobin was studied spectrophotometrically. The difficulty in discriminating the spectral changes upon oxygen binding to the alpha or beta subunit can be surmounted by means of multidimensional spectroscopic observations and a correlation analysis of the data. M-type abnormal haemoglobins are used as a control against normal haemoglobin because only one type of its subunits can bind oxygen. A multidimensional spectroscopic measuring system, which has been developed in our laboratory, makes it possible to carry out simultaneous and continuous acquisition of a set of spectroscopic data at several wavelengths on one sample solution during the course of increasing or decreasing the partial pressure of oxygen. The data-storing function of a magnetic disk memory provides enough precision for a rigorous investigation of the correlation of oxygen equilibrium curves measured at several wavelengths. No chemical modification to enhance the spectral difference between subunits is necessary. In conclusion, by detecting slight differences between the oxygenation-sensitive bands of alpha and beta subunits, the beta subunits are found to have a higher affinity for oxygen than the alpha subunits.

Allosteric Site↗

Inhibition by alpha 2-adrenoceptor agonists of the secretion of catecholamines from isolated adrenal medullary cells.

In adrenal medullary cells, carbachol evokes the secretion of catecholamines with simultaneous uptake of 45Ca. Highly selective agonists for alpha 2-adrenoceptors, clonidine, naphazoline, guanfacine, tramazoline and oxymetazoline inhibited carbachol evoked secretion of catecholamines in a dose-dependent manner. These alpha 2-agonists also inhibited the uptake of 45Ca evoked by carbachol with similar dose-response curve to inhibition of catecholamine secretion. On the contrary, highly selective agonists for alpha 1-adrenoceptors, phenylephrine and norfenefrine did not inhibit the secretion of catecholamines and cellular uptake of 45Ca. The inhibition by alpha 2-agonists was not restored either by the increase in carbachol or Ca concentrations, suggesting that the mode of inhibition was distinct from competition at cholinergic receptors or Ca-channels. It is likely that alpha 2-agonists inhibited the secretion of catecholamines via the inhibition of Ca uptake which was probably caused through the activation of alpha 2-adrenoceptors.

Adrenal Medulla↗