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Biomedical subjects

K Adachi

Publications and source records attributed to K Adachi.

At least 631 records · Page 35Linked to original sources

Nucleation-controlled aggregation of deoxyhemoglobin S. Effect of organic phosphates on the kinetics of aggregation of deoxyhemoglobin S in concentrated phosphate buffer.

The kinetics of the aggregatin of deoxyhemoglobin S in concentrated phosphate buffer were studied turbidimetrically in the presence of organic phosphates. The addition of inositol hexsphosphate shortened the delay time by 35-80%, the range depending on the hemoglobin concentration. The logarithmic plot of delay time versus hemoglobin concentration in 1.85 M potassium phosphate buffer, pH 7.34, showed a linear relationship with a slope (n value) of 2.5 +/- 0.14 in the absence of inositol hexaphosphate, while the slope was decreased to 2.1 in the presence of inositol hexaphosphate. The turbidity (A700) of aggregates per g deoxy Hb S was found to be lower in the presence of inositol hexaphosphate than in the absence of inositol hexaphosphate. The solubility of deoxy Hb S was decreased by inositol hexaphosphate. 2,3-Diphosphoglyceric acid also showed an effect similar to that of inositol hexaphosphate. However, if the pentacyclohexylammonium salt of diphosphoglyceric acid were used, the delay time was increased significantly. The opposite effect of the pentacyclohexylammonium salt of diphosphoglyceric acid on the delay time was found to be attributed to the anti-gelation effect of the pentacyclohexoxylammonium ion. The difference in the effect of inositol hexaphosphate and diphosphoglyceric acid on the delay time appears to be related to their effect on the solubility of deoxy Hb S.

Diphosphoglyceric Acids↗

Synthesis of ribosomal protein S1 following nutritional shift-up in Escherichia coli K-12.

The synthesis rate of ribosomal protein S1 was measured in Escherichia coli K-12 during the transitional period following a nutritional shift-up from acetate minimal to glucose/amino acids/nucleosides medium. The synthesis rate of S1 increased without a lag suggesting that the S1 gene is under stringent control and located very close to its promoter. The rate of S1 synthesis slowed between 7 and 15 min, and then increased to the postshift-up steady state rate. The postshift-up steady state rate was half the initial rate obtained between 0 and 7 min. The slow down in the synthesis rate between 7 and 15 min indicates that an unknown factor(s), in addition to guanosine 5'-diphosphate, 3'-diphosphate, participates in the regulation of S1 gene expression.

Acetates↗

Effect of cetiedil on erythrocyte sickling: new type of antisickling agent that may affect erythrocyte membranes.

The antisickling effect of cetiedil, alpha-cyclohexyl-3-thiopheneacetic acid 2-(hexahydro-1H-azepin-1-yl)-ethyl ester, has been investigated. The concentration of cetiedil required for 50% inhibition of erythrocyte sickling was about 140 micro M. An antisickling effect was achieved regardless of whether cetiedil was added before or after deoxygenation. The minimal gelling concentration of deoxy Hb S was increased by less than 10% in the presence of 218 micro M cetiedil. The oxygen equilibrium curves of Hb S were not significantly affected by cetiedil. Erythrocytes treated with high concentrations of cetiedil were swollen and became spheroidal. The antisickling effects of cetiedil might be due to an effect on erythrocyte membranes.

Antisickling Agents↗

Stimulation of protein phosphorylation by epidermal growth factor in pig skin (epidermis).

Incorporation of 32P-orthophosphoric acid into pig epidermal proteins was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The incorporation was observed in 2 major and 2 minor peaks with approximate molecular weights of 52,000 and 27,000, 17,000, and 12,000 respectively. Treatment with epidermal growth factor (EGF) consistently increased 32P incorporation into all 4 peaks. The stimulation was both time- and dose-dependent, and was not inhibited by the simultaneous addition of cycloheximide. In our previous study (submitted to J Invest Dermatol), we observed that EGF increased the cyclic GMP level in the same pig skin (epidermal) system. The possibility that the increased cyclic GMP leads to the protein phosphorylation observed in the present study was considered but ruled out because (1) the addition of cyclic GMP does not mimic the EGF treatment, (2) simultaneous addition of EGF and cyclic GMP stimulate phosphorylation to the same degree as the addition of EGF alone and (3) EGF stimulates phosphorylation in 20 min whereas the EGF induced increase in the cyclic GMP level takes 60 min.

Animals↗

Metabolic fate of SCE-1365, a new broad-spectrum cephalosporin, after parenteral administration to rats and dogs.

Disposition of [14C]SCE-1365 was studied in rats and dogs after intramuscular or intravenous injection. The plasma level of [14C]SCE-1365 peaked at 15 min after intramuscular administration and declined rapidly to give half-lives of 27 and 39 min, respectively, in rats and dogs. After intravenous dosage, half-lives were 22 and 32 min, respectively, in rats and dogs. In both animals, the plasma levels of 14C were made up largely of unchanged antibiotic. Binding to plasma protein was 91 and 31%, respectively, in rats and dogs. Tissue levels of [14C]SCE-1365 administered intramuscularly to rats peaked at 15 min and were highest in the kidney and lowest in the brain, with plasma, liver, lung, heart, intestinal wall, and adrenal gland occupying intermediary positions in the order listed. The concentration of [14C]SCE-1365 in erythrocytes was very low, as was the level of the antibiotic in rat fetuses. The milk of rats given [14C]SCE-1365 intramuscularly contained detectable levels of 14C. [14C]SCE-1365 was completely eliminated from the bodies of rats and dogs within 24 to 48 h. In both animals, a large amount of the dosed 14C was excreted in urine as unaltered antibiotic. The remainder was eliminated in the feces via bile. In rats, [14C]SCE-1365 was eliminated by both glomerular filtration (33%) and tubular secretion (67%). An active transport process appeared to be involved in biliary excretion in rats.

Absorption↗

Cyclic GMP system in the epidermis.

A great deal of knowledge has been gained concerning the activation of adenylate and guanylate cyclase in epidermal cells. Adenylate cyclase is activated by 4 different independent receptors-responding respectively to catecholamine (beta), to prostaglandins (E), to histamine (H2), and to adenosine and it phosphorylated derivatives. Upon activation, each of these receptors becomes unresponsive to further stimulation by its specific stimulator. Guanylate cyclase, on the other hand, is activated by histamine (H1) and epidermal growth factor (EGF). Unlike EGF, the histamine activation is extremely rapid (less than 5 minutes). Epidermal cells are permeable (leak) to cyclic GMP but not cyclic AMP. When the skin is traumatized or injured in any way (even by intradermal injection) there is a sudden catastrophic change in the intracellular levels of the cyclic nucleotides (and of ATP). Cyclic AMP rapidly rises to perhaps 5-10 times its normal resting level while cyclic GMP falls to 10-20% of its level in vivo. The rise in cyclic AMP is due to activation of adenylate cyclase while the fall in cyclic GMP is due in major part to activation of cyclic GMP phosphodiesterase (and perhaps the fall in ATP is due to activation of ATPase). The changes in ATP and cyclic AMP can be reversed by incubating the tissue in a buffered salt solution containing glucose, but this does not normalize the cyclic GMP content. The fall in cyclic GMP can be prevented by a phosphodiesterase inhibitor (IBMX ). This series of events has been called the "ischemia effect." However, it implies that a lack of oxygen is at fault, and that has not been shown to be the case. Its underlying cause and possible physiologic significance are not known. Do these changes in cyclic nucleotides have effects on epidermal proliferation? And does EGF? Agents which increase cyclic AMP do inhibit the epidermal outgrowth and mitotic activity of explant cultures of pig skin. Cyclic GMP does increase outgrowth at a particular concentration. Histamine, which elevates both cyclic nucleotides, has a biphasic action depending on its concentration. These findings imply that these nucleotides do act as one of the controls of epidermal proliferation. The action of cyclic GMP is not accompanied by detectably increased phosphorylation of epidermal proteins. On the other hand, EGF action which also enhances epidermal outgrowth is characterized by an increased protein phosphorylation that precedes any increase in cellular cyclic GMP. We conclude that the action of EGF is independent of the cyclic nucleotide system.

3',5'-Cyclic-GMP Phosphodiesterases↗

Permeability into aortic intima and atherosclerotic plaque.

For the purpose of examining the interrelation between the permeability of the plasma constituents and the site of the atherosclerosis. We have perfused the solution of a dye into human aorta and observed permeability into aortic intima with aging and into atherosclerotic plaque. In addition, the deposition of bilirubin and fibrin into atherosclerotic plaque was also investigated. When the extent of the permeability was expressed as the ratio of the depth of permeability/thickness of intima, it was found that the ratio for the thoracic aorta decreased with advancing age. Permeability of the abdominal aorta occurred to show that the value of the ratio was up to 3.0 in the subject with age from 0 to 19 years and then the ratio slightly decreased with advancing age, followed by a further one step down in the seventies. Permeability into the atheromatous plaque showed diffuse pattern in the young adult but the permeability became shallower with advancing age. Regional difference of permeability around the plaque was studied. The greatest permeability was seen on the lower side of the plaque. Bilirubin and fibrin deposition into plaque was also similar to its permeability pattern.

Adolescent↗

Epidermal cyclic AMP is not decreased in psoriasis lesions.

The cyclic AMP level in epidermis of psoriatic patients was reappraised with a highly sensitive radioimmunoassay method in conjunction with an improved skin biopsy technique to avoid any artificial rise of cyclic AMP due to ischemia. Local intradermal injection before biopsy was avoided, since even saline injection caused a clear-cut ischemia effect. The results concur with our previous study: i.e., on a tissue dry weight or protein basis, the cyclic AMP level in the involved epidermis is 20% higher than that in the uninvolved spidermis of psoriatic patients, and on a DNA basis, there was no significant difference. The cyclic AMP level in normal epidermis from non-psoriatic subjects is the same as that in the uninvolved epidermis of psoriatic patients. Such characteristics in psoriatic lesions as the increased mitosis, incomplete, differentiation and increased glycogen content cannot be simply related to a cyclic AMP deficiency.

Cyclic AMP↗

[Vaginal radical hysterectomy with and without systemic extraperitoneal pelvic lymphadenectomy for cervical cancer. A report of 666 patients operated upon between the years 1957 and 1973 (author's transl)].

The report presents 850 patients with cervical cancer operated with vaginal method 1957-1973. Vaginal radical hysterectomy and systemic extraperitoneal pelvic lymphadenectomy were done in 590 patients. A 5 year survival rate in Stage I was 90.4%, in Stage II 76.5%, and in Stage III 72.2%. The 10 survival rate for 462 patients were 86.1, 69.9 and 44.4% respectively. No operative mortality has occurred to date. The incidence of lymph node metastasis in stage I was 9.5%, in Stage II 25.9% and in Stage III 34.9%. The 5 year survival rate of the patients without lymph node metastasis was 88.2% and of those with lymph node metastasis 49.5%. Radical vaginal hysterectomy without the removal of regional lymph node were done in 76 patients. The 5 year survival rate was 86.8%. There was one postoperative death in this series. Vaginal hysterectomy were done in 184 patients. The 5 year survival rate was 92.4%.

Adolescent↗