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Biomedical subjects

A Kawaguchi

Publications and source records attributed to A Kawaguchi.

At least 163 records · Page 9Linked to original sources

Temperature- and growth-phase-dependent changes in membrane fatty acid compositions of Brevibacterium ammoniagenes.

Fatty acids newly synthesized by Brevibacterium ammoniagenes grown at different temperatures were analyzed. The assay temperature, not the growth temperature, was found to be the major factor affecting the unsaturated/saturated ratio of newly synthesized fatty acids in logarithmic-phase cells. However, in the stationary-phase cells the growth temperature also affected the product profile significantly; cells grown at 7 degrees C produced relatively more oleate and stearate and less palmitate and hexadecenoate when shifted up to 37 degrees C than did cells grown and assayed at 37 degrees C. The unsaturated/saturated ratio as well as average chain length of fatty acids also varied along with the progress of isothermal growth phase. These changes in fatty acid product profiles observed in vivo could be mimicked in vitro assays of the fatty acid synthetase by changing malonyl-CoA concentrations. Our results suggest that the malonyl-CoA concentration is a factor which, in addition to temperature, determines growth-phase-dependent and growth-temperature-dependent changes in the unsaturated/saturated ratios of fatty acids.

Acetates↗

T-lymphocyte analysis in cardiac allograft recipients treated with cyclosporine.

To assess the usefulness of circulating T-lymphocyte analysis in cardiac transplantation, T helper (Th) and T suppressor-cytotoxic (Ts-c) subsets were serially monitored in 33 cardiac allograft recipients treated with cyclosporine. The short-term prognosis of their 47 treated rejection episodes were retrospectively correlated with the changes in T-cell subpopulations. The data indicate three main findings. Reversed Th to Ts-c ratio (less than 1) was associated with a reduced incidence of rejection onset and a benign clinical course after treatment for rejection. Reversed Th:Ts-c ratio caused by antirejection therapy was associated with less chance of recurrence during the rest of hospitalization, regardless of the mode of therapy and irrespective of whether the rejection was primary or recurrent. These changes were mainly mediated by a reduction in T helper cells rather than changes in the T suppressor-cytotoxic subset or total T cells. Titration of antirejection therapy based on these T-cell dynamics may reduce either overtreatment or undertreatment. A prospective randomized study seems warranted to evaluate this approach as an alternative to a predetermined antirejection protocol.

Cyclosporins↗

Afferent reinnervation of the autotransplanted heart in dogs.

Patients have been observed with a chest pain syndrome after cardiac transplantation. For this pain to be cardiac in origin the afferent nerves carrying sensory information from the heart would have to reinnervate the heart. A previous study in dogs indicated that afferent reinnervation is uncommon during the first 2 years after transplantation. The purpose of this study was to determine whether afferent reinnervation of the heart occurs in the long term. The decreases in arterial pressure and renal nerve activity resulting from chemical stimulation of left ventricular sensory receptors with vagal afferents with cryptenamine (veratrum alkaloid) were assessed in three dogs 8 to 12 years and in four dogs 6 to 8 weeks after cardiac autotransplantation and in six sham-operated dogs (thoracotomy-pericardiotomy 6 to 8 weeks before study). Responses of renal nerve activity to physiologic stimulation of cardiac receptors by volume expansion were also determined. Left ventricular cryptenamine inhibited renal nerve activity by 72 +/- 8% in dogs with long-term and by 10 +/- 6% in dogs with short-term autotransplantation and by 92 +/- 5% in sham-operated dogs. Decreases in mean arterial pressure in these groups were 34 +/- 4, 11 +/- 3 and 67 +/- 16 mm Hg, respectively. Volume expansion inhibited renal nerve activity in long-term autotransplant (43%) and sham-operated (48%) groups but less in the short-term transplant group (33%) for comparable increases in cardiac filling pressure. It is concluded that in dogs there is extensive afferent reinnervation of the long-term autotransplanted heart that results in relatively normal cardiopulmonary baroreflex responses to volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Myocardial norepinephrine, epinephrine and dopamine concentrations after cardiac autotransplantation in dogs.

Myocardial norepinephrine is markedly reduced after cardiac transplantation because of interruption of postganglionic cardiac sympathetic nerves. There are also substantial stores of dopamine in the myocardium, but the influence of cardiac denervation on dopamine remains unknown. The effect of cardiac transplantation was determined and, thus, the effect of denervation on myocardial norepinephrine, dopamine and epinephrine. Myocardial catecholamines were measured with high-performance liquid chromatography with electrochemical detection in five dogs 6 to 8 weeks and in four dogs 8 to 12 years after cardiac autotransplantation and in six sham-operated dogs with intact cardiac innervation. Norepinephrine, dopamine and epinephrine levels were determined from samples obtained from the right and left atria and ventricles. Samples from the left ventricular apex and base were analyzed separately. There was a striking depletion of norepinephrine in all cardiac chambers after short-term autotransplantation. The norepinephrine content of the left atrium in sham-operated dogs (1,659 +/- 219 ng/g) was significantly higher than that of dogs with long-term autotransplanted hearts (754 +/- 372 ng/g). Sham-operated dogs and dogs with long-term autotransplanted hearts had statistically significant (p less than 0.05) differences in norepinephrine content in the left ventricular apex (480 +/- 197 versus 294 +/- 198 ng/g), left ventricular base (876 +/- 2204 versus 654 +/- 156 ng/g) and right ventricle (766 +/- 133 versus 247 +/- 29 ng/g). In contrast to norepinephrine, dopamine concentrations were relatively preserved in the short-term group despite the virtual depletion of myocardial norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum Oxide↗

Stereochemistry of 2,3-alkanediols obtained from the Harderian gland of Mongolian gerbil (Meriones unguiculatus).

The stereochemistry of the alcohol moieties of 2,3-alkanediol diacyl esters obtained from the Harderian gland of the Mongolian gerbil was investigated. There were five major 2,3-alkanediols, C14-C22 (even carbon numbers), all having the erythro configuration as determined by GC-MS analysis of their isopropylidene derivatives in comparison with synthetic erythro- and threo-2,3-hexadecanediols. 13C-NMR spectroscopy of the synthetic materials showed distinct differences of chemical shift at the C-1, C-3, and C-4 carbons, from which the native 2,3-alkanediols were definitely determined to be in the erythro series. The absolute configurations of the C-2 and C-3 asymmetric centers were assigned as 2S and 3R, respectively, based on known 2S,3R-octanediol.

Animals↗

Effect of thiolactomycin on the individual enzymes of the fatty acid synthase system in Escherichia coli.

Thiolactomycin, an antibiotic with the structure of (4S)-(2E,5E)-2,4,6-trimethyl-3-hydroxy-2,5,7-octatriene-4-++ +thiolide, selectively inhibits type II fatty acid synthases. The mode of the thiolactomycin action on the fatty acid synthase system of Escherichia coli was investigated. Of the six individual enzymes of the fatty acid synthase system, [acyl-carrier-protein] (ACP) acetyltransferase and 3-oxoacyl-ACP synthase were inhibited by thiolactomycin. On the other hand, the other enzymes were not affected by this antibiotic. The thiolactomycin inhibition of the fatty acid synthase system was reversible. As to ACP acetyltransferase, the inhibition was competitive with respect to ACP and uncompetitive with respect to acetyl-CoA. As to 3-oxoacyl-ACP synthase, the inhibition was competitive with respect to malonyl-ACP and noncompetitive with respect to acetyl-ACP. The thiolactomycin action on the fatty acid synthase system was compared with that of cerulenin.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

Characterization of the fatty acid synthetase system of Curtobacterium pusillum.

Curtobacterium pusillum contains 11-cyclohexylundecanoic acid as a major component of cellular fatty acids. A trace amount of 13-cyclohexyltridecanoic acid is also present. Fatty acids other than omega-cyclohexyl fatty acids present are 13-methyltetradecanoic, 12-methyltetradecanoic, n-pentadecanoic, 14-methylpentadecanoic, 13-methylpentadecanoic, n-hexadecanoic, 15-methylhexadecanoic, 14-methylhexadecanoic, and n-heptadecanoic acids. The fatty acid synthetase system of this bacterium was studied. Various 14C-labeled precursors were added to the growth medium and the incorporation of radioactivity into cellular fatty acids was analyzed. Sodium [14C]acetate and [14C]glucose were incorporated into almost all species of cellular fatty acids, the incorporation into 11-cyclohexylundecanoic acid being predominant. [14C]Isoleucine was incorporated into 12-methyltetradecanoic and 14-methylhexadecanoic acids: [14C]leucine into 13-methyltetradecanoic and 15-methylhexadecanoic acids; and [14C]valine into 14-methylpentadecanoic acid. [14C]-Shikimic acid was incorporated almost exclusively into omega-cyclohexyl fatty acids. The fatty acid synthetase activity of the crude enzyme preparation of C. pusillum was reconstituted on the addition of acyl carrier protein. This synthetase system required NADPH and preferentially utilized cyclohexanecarbonyl-CoA as a primer. The system was also able to use branched- and straight-chain acyl-CoAs with 4 to 6 carbon atoms effectively as primers but was unable to use acetyl-CoA. However, if acetyl acyl carrier protein was used as the priming substrate, the system produced straight-chain fatty acids. The results imply that the specificity of the initial acyl-CoA:acyl carrier protein acyltransferase dictates the structure of fatty acids synthesized and that the enzymes catalyzing the subsequent chain-elongation reactions do not have the same specificity restriction.

Acetyltransferases↗

Heart and unilateral lung transplantation in the dog.

A technique is presented for transplantation of the heart and left lung en bloc in the dog. In contrast to the erratic respiratory pattern that occurs in subprimate animals after total cardiopulmonary denervation, preservation of innervation to the native right lung results in a normal respiratory pattern in the dog and has allowed survival of one animal for 68 days. This model is proposed as potentially suitable for physiologic and immunologic studies of cardiopulmonary transplantation in the dog.

Animals↗

[Clinical evaluation of CEA in colorectal carcinoma].

Carcinoembryonic antigen (CEA) titer (Dinabot-Kit) were determined in proven 177 patients with colorectal carcinoma preoperatively, and at routine intervals following operation. The assay was positive in 39.1% with stage I, II, 65.9% with III, 65.9% with IV and 85.7% with V. Elevated CEA levels were noted in those who had infiltration of cancer cells extending through the proper muscle layer. In 79.2% of curative resections CEA levels returned to normal within one month, but the titers remained elevated in 73.3% of palliative resections. Among 26 patients with recurrent disease, 16 had a hepatic metastasis showing a previous or simultaneous CEA rise, whereas 10 had a local recurrence with a slow rise or normal. In addition, a quantitative study of CEA in extracts of 87 tumors was made in order to examine the factors affecting the level of circulating CEA. There was no significant difference between the CEA contents of the tumor and its level of circulating CEA. The level of circulating CEA might be influenced by the spread cancer cells, rather than the tumor contained CEA.

Carcinoembryonic Antigen↗

Stereospecific incorporation of hydrogens from NADPH in elongation of very long fatty acyl-CoA by swine cerebral microsomes.

The elongation of arachidoyl-CoA by swine cerebral microsomes resulted in the production of behenic acid (22:0) and lignoceric acid (24:0) concomitantly. When 4S-[4-2H1]NADPH was used for the elongation of arachidoyl-CoA, the incorporation of two deuterium atoms into 22:0 was observed by the technique of mass fragmentography. Furthermore, the incorporation of four deuterium atoms into 24:0 was also detected. On the other hand, when 4R-[4-2H1]NADPH was used, no deuterium was incorporated into the elongated products.

Acyl Coenzyme A↗

Mycotic aortic aneurysms in children.

Mycotic aneurysms of the aorta are uncommon in babies and children. Prior to the development of antibiotics, most mycotic aneurysms were seen secondary to bacterial endocarditis, but this is now uncommon. Instead, more cases have been reported as complications of umbilical artery catheters in newborns. We have seen five cases of mycotic aneurysms in children, two of them secondary to umbilical artery catheters. One patient had coarctation of the aorta, and the other patients had different sources of infection. Three patients were treated surgically by us with good results after antibiotic therapy. One patient died of sepsis before the aneurysm was diagnosed. The fifth patient was treated elsewhere and now has a recurrent aneurysm. We think a combination of aggressive medical and early surgical therapy may save a high percentage of these patients.

Aneurysm, Infected↗

Studies on the metabolism of unsaturated fatty acids. XIII. Properties of 2,4-dienoyl-CoA reductase from beef liver.

It is demonstrated that 3-alkenoyl-CoA is the product of the enzymic reduction catalyzed by 2,4-dienoyl-CoA reductase with the highly purified enzyme preparation from beef liver mitochondria. Incorporation of deuterium atoms from deuterium-labeled NADPH and 2H2O during the reaction catalyzed by 2,4-dienoyl-CoA reductase from beef liver was investigated. When trans-2, trans-4-decadienoyl-CoA was incubated with the reductase in the presence of 4R-[4-2H1]NADPH and H2O, no deuterium was detected in the reaction product by gas chromatography-mass spectrometry after derivatization to pyrrolidine amides of fatty acids. When the substrate was incubated with the enzyme in the presence of 4S-[4-2H1]NADPH and H2O, one deuterium atom was incorporated into the product, 3-decenoate, at the C-5 position. In the case of 3-decenoate enzymatically prepared in the presence of NADPH and 2H2O, two deuterium atoms were incorporated into the product at the C-2 position. These results indicate that the reaction catalyzed by 2,4-dienoyl-CoA reductase from beef liver is a unique example of 1,4-addition of hydrogen to a 1,3-diene system conjugated with a carbonyl group of a thioester in biochemical fields. Chain length specificity of the reductase, isotope effects on reaction rates and competitive inhibitors are also discussed.

Animals↗

Cerulenin resistance in a cerulenin-producing fungus. II. Characterization of fatty acid synthetase from Cephalosporium caerulens.

Cerulenin, an antifungal antibiotic isolated from a culture filtrate of Cephalosporium caerulens, is a potent inhibitor of fatty acid synthetase systems of various microorganisms and animal tissues. This antibiotic specifically blocks the activity of beta-ketoacyl thioester synthetase (condensing enzyme) by binding to the functional cysteine-SH in the active center of the condensing enzyme domain (the peripheral SH-group). However, fatty acid synthetase from C. caerulens is much less sensitive to cerulenin than fatty acid synthetases from other sources. The properties of C. caerulens synthetase were investigated and compared to those of Saccharomyces cerevisiae synthetase, which is sensitive to the antibiotic. The molecular weight of the enzymically active form of C. caerulens synthetase was 2.53 X 10(6). The enzyme consisted of two multifunctional proteins, alpha and beta, which are arranged in a complex, alpha 6 beta 6. The synthetase was inactivated by iodoacetamide. At 0 degrees C and pH 7.15, the second-order rate constant of k = 15.6 M-1 X s-1 was obtained for the inactivation by iodoacetamide. This value was about 15 times greater than that for S. cerevisiae synthetase. Treatment of C. caerulens synthetase with iodoacetamide, while impairing the synthetase activity, induced malonyl-CoA decarboxylase activity. When S. cerevisiae synthetase was preincubated with cerulenin, malonyl-CoA decarboxylase activity could not be detected even after treatment of the enzyme with iodoacetamide (Kawaguchi, A., Tomoda, H., Nozoe, S., Omura, S., & Okuda, S. (1982) J. Biochem. 92, 7-12). In the case of C. caerulens synthetase, on the other hand, malonyl-CoA decarboxylase activity was induced by iodoacetamide even after the preincubation of the enzyme with cerulenin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acremonium↗