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Biomedical subjects

K Adachi

Publications and source records attributed to K Adachi.

At least 613 records · Page 34Linked to original sources

Effect of piracetam on sickle erythrocytes and sickle hemoglobin.

Piracetam, 2-oxo-1-pyrrolidine acetamide, inhibits sickling of red cells containing sickle hemoglobin (Hb S). The concentration required for 50% inhibition is about 300 mM. Addition of piracetam into the supersaturated Hb S solution in concentrated phosphate buffer prolongs the delay time prior to gelation. Piracetam shifts the oxygen equilibrium curves of blood toward the right, with a stronger effect at higher piracetam concentrations. Piracetam increases the viscosity of oxygenated cells but reduces the relative viscosity of deoxygenated sickle cells. The mechanism for the antisickling effect of piracetam will be discussed.

Anemia, Sickle Cell↗

Aggregation and crystallization of hemoglobins A, S, and C. Probable formation of different nuclei for gelation and crystallization.

The oxy and carbonmonoxy forms of Hb A and Hb S formed aggregates or gels when dissolved in phosphate buffers at concentrations above their solubility and warmed rapidly to 30 degrees C from 0 degrees C. Kinetic studies showed that although deoxy-Hb A and deoxy-Hb S aggregated with a clear exhibition of a delay time, the oxy and carbonmonoxy forms of Hb A and Hb S did not show a delay time. These results suggest that the deoxy forms of Hb A and Hb S aggregate according to the nucleation-controlled mechanism, while oxy- and carbonmonoxyhemoglobins aggregate by the simple linear aggregation mechanism. It was also found that the gels or aggregates of deoxy-Hb A and carbonmonoxy-Hb S could be converted to crystals by further incubation. The rate of crystallization depended upon the concentration of hemoglobin in the supernatant, with faster crystallization at higher concentrations. Similar experiments with deoxy-Hb C (beta 6 Glu leads to Lys) showed that this hemoglobin also crystallized after aggregation, with both reactions accompanied by a delay time. The activation energy for the crystallization reaction of deoxy-Hb C (100 approximately 150 kcal/mol) was much higher than that for the aggregation reaction (20 kcal/mol). These results suggest that deoxy-Hb A, deoxy-Hb S, and deoxy-Hb C form two types of nuclei that are specific to the formation of gels (or aggregates) or crystals. The concentration of hemoglobin measured after completion of crystallization was much lower than that measured after gelation (or aggregation) and was independent of the initial hemoglobin concentration. This concentration is assumed to be the real solubility of hemoglobin.

Crystallization↗

Activation of cAMP-dependent protein kinase in epidermis by the compounds which increase epidermal cAMP.

Pig epidermal slices were incubated with various compounds which increased epidermal cAMP (adenosine 3',5'-monophosphate), and the change in cAMP-dependent protein kinase activity ratio was studied by the method of Cherrington et al (J Biol Chem 251:5209-5218, 1976) with modification. Epinephrine (5 x 10(-5) M), histamine (10(-4) M) and adenosine (10(-3) M), potent agonists of epidermal adenyl cyclase, fully activated the protein kinase (PK) during an incubation of 30 to 45 seconds, that was much shorter than that required for maximal cAMP accumulation under the same conditions (5 min). With such a brief stimulus, the epidermal cAMP-PK system did not become refractory and responded to repeated stimuli. Prostaglandin E2 (PGE2) and isobuthylmethylxanthine (IBMX) and ethanol only partially activated the enzyme. Prostaglandin F2 alpha (PGF2 alpha) and theophylline which were much less effective in increasing epidermal cAMP, activated the enzyme to the same extent as PGE2 and IBMX respectively. These results suggest that protein kinase activation takes place in response to a cAMP increase in small locus of the cell. Such an increase in cAMP can be very small or even not measurable when measured as total cAMP in the tissue homogenate. Also, increases above this level may not be physiologic. It is concluded that measurement of cAMP-dependent protein kinase activity ratio is a more direct and more sensitive way to study the effect of compounds which act through cAMP mediated mechanisms.

Adenosine↗

Epidermal cyclic GMP is increased in psoriasis lesions.

Cyclic GMP levels in epidermis of normal subjects and of psoriatic patients were measured with a highly sensitive radioimmunoassay method. Technical improvements for the assay are 2-fold: (1) skin samples were frozen in vivo before biopsy and local injection of any anesthetic was avoided to overcome ischemia effect which could lower cyclic GMP artificially; (2) epidermis was microdissected to avoid contamination of dermis and keratin layers. The results show that on a per mg tissue dry weight basis the cyclic GMP levels are about 200 fmol in the involved lesional epidermis and 70 fmol in the uninvolved or normal epidermis. Similarly increases in the cyclic GMP levels in the lesional epidermis are observed when the data are expressed either on a DNA or protein basis. The cyclic GMP level in normal epidermis from nonpsoriatic subjects is the same as that in the uninvolved epidermis of psoriasis patients.

Cyclic GMP↗

The effect of histamine on epidermal outgrowth: its possible dual role as an inhibitor and stimulator.

We have investigated the effect of histamine on pig epidermal cell outgrowths in vitro. Histamine inhibited the epidermal cell outgrowths (and also mitosis). This inhibition was partially counteracted by a specific H2 antagonist, cimetidine. Inhibition was maximal at a histamine concentration of 10(-4) M and was less at 10(-3) M. These histamine concentrations respectively coincide with the optimal concentrations for accumulating intracellular cyclic AMP (via H2 receptors) and cyclic GMP (via H1 receptors) in the same pig epidermal slice system. 4-Methyl-histamine, a pure H2 agonist, which only increased the intracellular cyclic AMP level but not the cyclic GMP level, caused a maximal outgrowth inhibition at 10(-3) M. Attempts to counteract the histamine effects due to cyclic GMP accumulation by various H1 antagonists (so that 10(-3) M histamine would have caused maximal outgrowth inhibition) were unsuccessful, since the addition of each H1 antagonist alone strongly inhibited the outgrowth. These data strongly suggest a dual role of histamine through the cyclic nucleotide system; i.e., histamine inhibits epidermal cell growth by elevating the intracellular cyclic AMP level via an H2 receptor, while histamine at high concentrations (10(-3) M) partially counteracts the inhibition by increasing cyclic GMP via an H1 receptor.

Animals↗

Bacteriology of acute obstructive suppurative cholangitis of the aged.

Bacteriological examination was performed on bile from 23 patients with acute obstructive suppurative cholangitis. Of 23 bile cultures, 15 yielded aerobic and anaerobic bacteria and 8 yielded aerobic bacteria only. No specimen grew anaerobic bacteria only. A total of 20 cultures yielded a polymicrobial flora, and 3 cultures grew one single aerobic bacterium. Escherichia coli, Klebsiella sp., enterococci, Bacteroids fragilis, and Clostridium perfringens were the predominant bacterial flora in bile of these patients. Bacteremia was documented in 10 of the 12 patients cultured. All bacteremias involved aerobic bacteria and were polymicrobial in three patients. The frequent presence of anaerobes in bile of patients with acute obstructive suppurative cholangitis suggests that antimicrobial therapy should provide adequate coverage for anaerobic bacteria and enteric organisms.

Acute Disease↗

An 18p- syndrome due to 15/18 translocation with facial palsy and deafness.

A case of translocation between chromosomes No. 15 and 18 was described. Phenotype of the patient was almost consistent with that of the 18p- syndrome. In addition to the typical feature of 18p- syndrome, he had perceptive deafness, and abducens nerve and facial nerve palsies. Giemsa-binding technique demonstrated patient's karyotype to be 45, XY, -15, -18, +t (15; 18).

Child, Preschool↗

Precipitation of oxyhemoglobins A and S by isopropanol.

The isopropanol precipitation test is widely used for the detection of unstable hemoglobins. A method for accurately and easily determining the amount of hemoglobin precipitated is described. This study demonstrates that changes in incubation time, pH, temperature, and isopropanol and hemoglobin concentrations affect the precipitation of oxy Hb A and oxy Hb S. Hb S shows greater precipitation than Hb A with increasing time, temperature, and isopropanol concentrations. Both hemoglobins show equal increases in precipitation, with increases and decreases in pH and decreases in hemoglobin concentration. Comparison of the isopropanol precipitation test with the mechanical shake and heat denaturation tests reveals that the mechanical shake test is the easiest method to study the stability of Hbs A and S. Each of the tests may measure different parameters of stability. The use of all three tests in the evaluation of unstable hemoglobins should be considered.

1-Propanol↗

Molecular stability of Hb Philly (alpha 2 beta 2 35(Cl) Tyr leads to Phe). Rhe relationship of hemoglobin stability to ligand state as defined by heat and mechanical shaking tests.

The molecular stability of Hb Philly (alpha 2 beta 2 35(Cl) Tyr leads to Phe) with different ligand states was compared with that of Hb A and Hb S using mechanical shaking and heat stability tests. The rates of mechanical denaturation of the oxy-forms of these hemoglobins decreased in the order of Hb S, Hb Philly, and Hb A, with relative ratios of 9.5: 5.6: 1.0. Upon oxidation to the met-forms, Hb Philly became mechanically most unstable, with ratios of 13.3: 23.0: 1.8, respectively. The deoxy-forms, of Hb A and Hb S were very stable, while that of Hb Philly was as unstable as the oxy-form. The addition of inositol hexaphosphate (IHP) to deoxy-Hb Philly stabilized the molecules. Since IHP restores the cooperative oxygen binding of Hp Philly, deoxy-Hb Philly appears to combine with IHP to change the quaternary structure required for cooperative oxygen binding and for stabilization of the molecule.

Drug Stability↗

Chirally selective synthesis of sugar moiety of nucleosides by chemicoenzymatic approach: L- and D-riboses, showdomycin, and cordycepin.

The symmetric dimethyl esters derived from furan and dimethyl acetylenedicarboxylate was efficiently hydrolysed with pig liver esterase to yield half esters with high optical purity. Following chemical transformations afforded precursors with L-configuration, and chirality transfer through ester exchange was achieved to afford precursors with D-configuration of the sugar moiety of nucleosides. Thus, an efficient approach to L- and D-riboses, showdomycin, and cordycepin (3'-deoxy-adenosine) has been demonstrated.U

Animals↗

[Surface ultrastructural cyclic change of the human uterine glandular and lining epithelia. A scanning electron microscopic study (author's transl)].

The purpose of this study is to take advantage of scanning electron microscopy on the topographic alterations of the human uterine glandular epithelium which occur during the various stages of the menstrual cycle. 1) Both glandular and lining epithelia were mainly covered with nonciliated cells which reflected the cyclical changes during the menstrual cycle. In the early proliferative phase, microvilli were short and the apical cellular membrane slightly protruded, however microvilli and the apical cellular membrane gradually developed toward the end of proliferative phase. Compared with the surface epithelium, the glandular epithelium showed a monotonous change because of the uniform surface structure. 2) Numerous ciliogenesis can be observed on the lining epithelium in the late proliferative phase. In contrast, ciliogenesis could not be recognized in the glandular epithelium. 3) In the glandular epithelium, an apocrine type of secretion was recognized for several days after ovulation and they were seen to cluster occasionally. It was suggested that the secretion activity differed among various parts of the endometrial gland. 4) The menopausal phase was divided into two groups: the early stage of the postmenopausal phase resembled the early proliferative phase and had a fusiform and flattened cells with slender microvilli. Ciliated cells were seen in clusters. On the other hand, the advanced postmenopausal phase had uniform flattened cells with sparse microvilli and ciliated cells were extremely rare. 5) The lining epithelium of a female fetus was recognized with a slight protrusion of the apical cellular membrane with long microvilli.

Adult↗