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Biomedical subjects

Y Eguchi

Publications and source records attributed to Y Eguchi.

At least 163 records · Page 9Linked to original sources

Enantioselective synthesis of cyclohexenone derivatives by a chemicoenzymatic approach: stereo- and regioselective route to potential intermediates of compactin (ML 236B) and mevinolin.

As a synthetic application of the chiral monoester 2, prepared by pig liver esterase (PLE)-catalyzed hydrolysis of the corresponding meso diester 1, conversion of 2 into various cyclohexenone derivatives was examined. This paper describes the preparation of the isomeric cyclohexenones 6 and 7, potential intermediates for the synthesis of anti-hypercholesmic compactin (ML 236B) and mevinolin, under stereo- and regioselective control.

Chemical Phenomena↗

Developmental changes in the umbilical arteries with observation of the effects of indomethacin in fetal rats.

The caliber of the umbilical arteries was measured in fetal rats on day 14 to 21 of gestation. The fetuses were rapidly frozen in an acetone-dry ice mixture. The caudal half of each whole-body frozen fetus was gradually shaved with a knife from the ventral side to expose the umbilical arteries for measurement of their calibers. Observation reveals that, on day 15 of gestation, the umbilical arteries are asymmetrical in that the right artery is more dilated than the left. It is further seen that the left umbilical artery is closed on day 17 in contrast to the right which is increasingly more dilated toward term. When indomethacin, a synthetic compound having an action similar to that of glucocorticoids, was administered to pregnant rats 3 hr prior to sacrifice on day 21 of gestation, the right fetal umbilical artery was significantly constricted. The reason for this phenomenon is unknown, but is discussed in association with the manner of closure of the ductus arteriosus.

Animals↗

Variation of trace metals in ancient and contemporary Japanese bones.

Excavated and contemporary bones (rib cortexes) of a mature age (40-60 yr) were analyzed by atomic absorption spectrometry for the concentration of seven elements, including Ca, Cd, Cu, Fe, Mn, Ni, and Pb, with a view to historically evaluating the chemical composition of the bones. Fifty-two well-preserved specimens, obtained from western Japan, were classified into six groups according to Japanese prehistoric and historic eras (Jomon, Yayoi, Kofun, Muromachi, Edo, and Contemporary). Average concentrations of Ca were 0.20-0.33 g/g in the excavated bones and 0.17 g/g in the contemporary bones. Among the trace metals, such as Cu, Fe, Mn, and Pb, which showed remarkably elevated concentrations in the Edo era bones, Cu, Fe, and Mn were found to be strongly associated with soil contamination. Lead levels only slightly increased between the Jomon and Kofun eras, but became abruptly elevated following the Edo era. In contrast, the concentrations of Cd increased abruptly in the Yayoi era to a level with an order of magnitude higher than the Edo era, and they have recently decreased to rather low contemporary levels. This tendency becomes clearer when comparing the molar ratio of trace metals to Ca. The cause of elevated Cd concentrations in early excavated bones is discussed in relation to the mineralization of bones and the surrounding environment.

Adult↗

Origin of müllerian duct and its later developmental changes in relation to wolffian duct in bovine fetuses.

At the 1.6-1.8 cm stages in both male and female bovine fetuses, the anlage of the Müllerian duct was first observed as an elevation of mesothelium on the cranial tip of the mesonephros. The duct extended toward the urogenital sinus in parallel with the Wolffian duct. Its caudal end was solid and was fused with the Wolffian duct at about the level of the middle of the gonadal anlage. Thereafter, the Müllerian duct became gradually independent of the Wolffian duct throughout its whole length. Therefore, it may be that the main part of the Müllerian duct is established by budding from the Wolffian duct. At the 4.3-4.5 cm stages the male Müllerian duct began to degenerate and the female one continued to grow. This suggests that the male Müllerian duct is affected by the Müllerian inhibiting substance at these stages. At the 12.0 cm stage, the female Wolffian duct disappeared. The male Wolffian duct was also much reduced in diameter at this stage, but began to grow again from the 14 cm stage onward.

Animals↗

Histological changes in the placenta induced by maternal alcohol consumption in the rat.

To investigate the placental enlargement which accompanies maternal alcohol consumption during pregnancy, Sprague-Dawley rats were given 20% ethanol for 4 weeks prior to mating and 30% ethanol throughout gestation. Pair-fed controls received an isocaloric amount of corn starch and chow, with water ad libitum, and ad libitum controls received rat chow and water. On days 17, 18, 19 and 20 of gestation, placentas were removed for histological observation. On days 18-20, the placentas of alcohol-fed rats weighted significantly more than did those of controls, although there was no difference in weight on day 17. Giant cells in the basal zone were significantly increased in number and size in alcohol-fed rats compared to controls. Trophoblastic cells in the basal zone were significantly larger in the alcohol group than in the control groups except on day 17. The maternal blood channels in the labyrinth were wider and more filled with blood corpuscles in the alcohol group than in either control group. It is concluded that the increased weight of the placenta may be largely due to stagnated maternal blood cells in the labyrinthine blood channels and also to the increased number and size of giant cells and the enlarged trophoblastic cells in the basal zone.

Animals↗

Compensatory adrenal hypertrophy following unilateral adrenalectomy of fetuses of rats given alcohol throughout gestation.

The effect of maternal alcohol consumption on fetal compensatory adrenal hypertrophy following unilateral adrenalectomy was studied in rats. Females were given 20% alcohol in tap water for 4 weeks prior to mating and 30% alcohol in tap water throughout gestation (alcohol), or were pair-fed to the alcohol group (pair-fed) or were fed ad libitum (control). On day 20, fetuses were unilaterally left-adrenalectomized or sham operated. Mothers were sacrificed on day 22 of gestation and right adrenals of adrenalectomized, sham-operated, and unoperated fetuses were removed and weighed. Some adrenals were fixed, sectioned, and stained for histological examination. Adrenalectomized fetuses of all three dietary treatment groups demonstrated compensatory hypertrophy. Adrenals of alcohol-exposed fetuses weighed less than those of pair-fed or control fetuses, and the ratio of adrenal weight/body weight was greater, regardless of surgical procedure. Histological sections of right adrenals of left-adrenalectomized fetuses showed larger cells and widened sinusoids, compared to unoperated fetuses in the corresponding dietary treatment groups. These results are consistent with a retardation in adrenal growth and development as a result of alcohol exposure, but show that alcohol consumption throughout gestation does not affect the ability of the adrenals to undergo compensatory hypertrophy following unilateral adrenalectomy.

Adrenal Glands↗

Ultrastructural evidence that the negative feedback mechanism of the pituitary-thyroid axis can operate without the hypothalamus in fetal rats: observation of thyroid follicular cells.

Hypothalamus-independent negative feedback mechanism of the pituitary-thyroid axis was studied by electron microscopic observation of thyroid follicular cells of encephalectomized or hypophysectomized fetal rats under hypothyroidism induced by propylthiouracil (PTU). Fetal hypophysectomy or encephalectomy was performed on day 19 of gestation. Mother rats were given either a daily amount of 40 mg PTU or saline alone on the day of operation and on the next day. On day 21, their fetuses were obtained. As a result, PTU induced marked goiters even in encephalectomized fetuses, the goiters being comparable in weight to those induced in littermate intact fetuses. Electron microscopically, the follicular lumen was narrowed, microvilli were lengthened with a marked increase in number, and rER was extremely expanded. Follicular cells often confined colloid droplets and lysosomes. Fetal hypophysectomy, even in PTU-treatment, caused a reduction in the thyroid weight, accompanied by flattening of follicular cells, shortening of microvilli, widening of follicular lumen, and shrinkage of rER. These findings would support the view that the negative feedback mechanism of the pituitary-thyroid axis can operate without the hypothalamus in fetal rats.

Animals↗

Relationship between the development of the gubernaculum and the testicular descent in the rat fetus: macroscopic and light and electron microscopic observation.

The gubernaculum consists of the gubernacular cord connected with the vas deferens and the gubernacular bulb connected with the retroabdominal wall. The cord was first distinguished on day 15 of gestation. Its length reached the peak on day 16, followed by a reduction until day 18 to be almost constant thereafter. The bulb was first distinguished on day 16, and its length was steadily increased toward term. The testis began to descend with a reduced length of the cord. By day 19, the testis descended close to the caudal part of the bulb by the sharp bending of the cord. Microscopically, the bulb consisted at first of a centrally located mesenchymal mass and of a covering layer of myoblasts. Thereafter, the mesenchymal mass was gradually shifted toward the cranial part of the bulb, trailing loose mesenchymal tissue in the caudal part of the bulb. On day 19, the mass was decreased in cell population but increased in amount of collagen fibers. It is suggested that the testicular descent starts on day 16 together with the commencement of shortening of the gubernacular cord and enlargement of the gubernacular bulb.

Animals↗

Origin of müllerian duct and its later development in relation to Wolffian duct and anogenital distance in the rat.

On day 14 of fetal life in the rat, Müllerian (paramesonephric) duct in both sexes was first observed close to Wolffian (mesonephric) duct. Its caudal end joined Wolffian duct at about the level of the middle of gonadal anlage. Thereafter, Müllerian duct became independent of Wolffian duct through its whole length. Therefore, the main part of Müllerian duct may be formed by budding from Wolffian duct. On day 16, the anogenital distance in male started to increase with thickening of Wolffian duct and disappearance of Müllerian duct. Castration of male fetuses on day 19 stopped later masculinizing development. Therefore, it is clear that the fetal testis is an organ crucial for the masculinization of the urogenital tract as it activates the secretion of masculinizing hormone(s).

Animals↗

Insulin autoimmune syndrome associated with benign monoclonal gammopathy. Evidence for monoclonal insulin autoantibodies.

A 64-yr-old man with benign monoclonal gammopathy developed recurrent episodes of severe hypoglycemia but lacked evidence of insulinoma or exogenous insulin administration. The patient's plasma was found to contain anti-insulin antibodies and large amounts of extractable insulin (1110 microU/ml), which was identified as human insulin by high-performance liquid chromatography (HPLC). The anti-insulin antibodies consisted solely of IgG and lambda-light chains. Scatchard analysis of these antibodies revealed an almost straight-line relationship, with markedly low affinity and high capacity. An immune complex made of 125I-labeled insulin and the patient's antibodies emerged in a molecular-sieve HPLC as almost a single peak, suggesting a homogeneous antibody population. In addition, the patient's M protein was separately shown to be the IgG and lambda-light-chain type. We suggest that the insulin autoantibodies responsible for the spontaneous hypoglycemia in this patient are monoclonal and of M protein origin.

Antibodies, Monoclonal↗

The immunoglobulin class, the subclass and the ratio of kappa:lambda light chain of autoantibodies to human insulin in insulin autoimmune syndrome.

The immunoglobulin class, subclass and the k:lambda light chain ratio of insulin autoantibodies were determined in the sera of twenty-four patients with insulin autoimmune syndrome. All sera proved to be of the IgG immunoglobulin class but exhibited various IgG1:IgG2:IgG3:IgG4 ratios. The ratio of k:lambda light chain ranged from 1:0.13 to 1:0.75 with the exceptions of two sera that were characterized as IgG1(k) and IgG1(lambda).

Adult↗

Effect of maternal alcohol consumption on the fetal thyroid in the rat.

To investigate the effect of maternal alcohol consumption on the development of the fetal thyroid gland, Sprague-Dawley rats were given 20% ethanol for 4 weeks prior to mating and 30% ethanol throughout gestation. Pair-fed controls received an isocaloric amount of corn starch and chow, with water ad libitum, and ad libitum controls received rat chow and water. On Days 17, 18, 19, and 20 of gestation, the fetuses were weighed and the fetal thyroids were removed for histometric observation. On Days 19 and 20, the fetal thyroids of alcohol-exposed fetuses weighed significantly less than those of the two control groups, but more than the control thyroids 1 day earlier. Maternal alcohol consumption caused a significant decrease in both the follicular cell height and the follicle diameter of the fetal thyroid on all days examined. In the alcohol group on Days 19 and 20 of gestation, the cell height was less than, and the follicle diameter was approximately equal to those in the two controls 2 days earlier. These results indicate that, as a consequence of maternal alcohol consumption, growth of the fetal thyroid gland is retarded, and there are indications of fetal hypothyroidism, as seen from the histometric data. This latter is suggestive of a retarded thyrotropic activity of the fetal pituitary gland.

Alcohol Drinking↗

[Synthetic studies of substituted quinazolinone].

We re-examined 2-methyl-3-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-4 (3H)-quinazolinone to be hydroxymethylated by means of selenium oxide oxidation, followed by Ca (BH4)2 reduction. Chlorination reaction of 2-hydroxymethyl quinazolinone proceeded effectively by use of PCl5 in anhyd. benzene at room temperature. Thus, we prepared new compounds in respect of substituted quinazolinone.

Quinazolines↗

Clot lysis induced by a monoclonal antibody against alpha 2-plasmin inhibitor.

A monoclonal antibody (MoAb) to alpha 2-plasmin inhibitor designated JTPI-1 inhibited antiplasmin activity by interfering with formation of alpha 2-plasmin inhibitor (alpha 2-PI)-plasmin complex. With this MoAb, we observed plasma clot lysis in vitro and evaluated the potential of JTPI-1 to serve as a new therapeutic agent for thrombolysis. After adding 125I-labeled fibrinogen to plasma, clots were made by adding thrombin and calcium and were then resuspended in normal plasma containing various concentrations of JTPI-1. The presence of JTPI-1 enhanced release of the soluble 125I-labeled fibrin degradation fragment from the clots in a dose-dependent manner. With tissue plasminogen activator (t-PA)-depleted plasma, we showed that induction of clot lysis by JTPI-1 was dependent on fibrin-bound endogenous t-PA. Regulation of fibrinolysis initiated on the fibrin surface by fibrin-bound t-PA and plasminogen is mediated by alpha 2-PI cross-linked to fibrin by activated factor XIII. JTPI-1 bound to this cross-linked alpha 2-PI neutralized its activity and induced partial digestion of fibrin by plasmin. This resulted in additional binding of Glu-plasminogen to fibrin during the incubation. When 1.2 mumol/L JTPI-1 and 5 U/mL exogenous t-PA were present in the suspending plasma, the rate of clot lysis was essentially the same as that induced by 60 U/mL exogenous t-PA alone. These results suggest that JTPI-1 may be useful in reducing the amount of t-PA administered for thrombolytic therapy.

Antibodies, Monoclonal↗

Two forms of RecA-single-stranded DNA-adenosine 5'-O-(3-thiotriphosphate) complexes with different activities for cleavage of phage phi 80 cI repressor.

The kinetics of cleavage of the phage phi 80 cI repressor by Escherichia coli RecA protein were studied. The rate of cleavage in the presence of single-stranded DNA (ssDNA) and either adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), ATP or dATP is very low in the first hour at 37 degrees C and then increases sharply as incubation continues. The initial rate of cleavage of the repressor is greatly increased by incubating the RecA protein with ssDNA prior to addition of ATP gamma S and the repressor. However, when ATP gamma S is present during preincubation of RecA protein with ssDNA, the stimulatory effect of preincubation is greatly reduced. This difference in the effect of preincubation in two different conditions can be explained by formation of RecA-ssDNA-ATP gamma S complexes with different activities for cleavage of the repressor. The active complex is formed by binding of ATP gamma S to a complex of RecA protein and ssDNA. However, when the RecA protein binds to ATP gamma S prior to its binding to ssDNA, the resulting complex has no or only very weak cleavage activity toward the repressor.

Adenosine Triphosphate↗

Stimulation of RecA-mediated cleavage of phage phi 80 cI repressor by deoxydinucleotides.

The presence of either deoxyguanylyl-(3'----5')-deoxyguanosine (d(G-G] or deoxyadenylyl-(3'----5')-deoxyguanosine (d(A-G] greatly stimulates cleavage of the phage phi 80 cI repressor mediated by the Escherichia coli RecA protein in vitro. No other deoxydinucleoside monophosphate or riboguanylyl-(3'----5')-guanosine (r(G-G] affects the cleavage reaction. Neither the cleavage site of the phi 80 cI repressor nor the requirement for single-stranded DNA and ATP for cleavage is altered by d(G-G). Photoaffinity labeling experiments with 32P-labeled 5'-phosphoryl deoxyguanylyl deoxyguanosine (pd(G-G], which also stimulates cleavage, show that pd(G-G) bound to the repressor under the conditions in which the repressor is cleaved by RecA protein. The binding increases the affinity of the repressor for RecA protein and thus greatly stimulates repressor cleavage. The cleavage reactions of LexA and lambda cI repressors by RecA protein are not affected by d(G-G).

Bacterial Proteins↗

Phasic coronary artery flow velocity determined by Doppler flowmeter catheter in aortic stenosis and aortic regurgitation.

Phasic coronary artery flow velocity was recorded in 14 patients with aortic regurgitation (AR), 4 with aortic stenosis, 61 with other heart diseases and in 2 normal subjects by means of a bidirectional Doppler flowmeter catheter. The normal pattern of the phasic coronary artery flow velocity was characterized by a small forward flow during systole (S wave) and a large forward flow during diastole (D wave). The phasic coronary artery flow velocity in patients with AR showed increased S wave and decreased D wave. The area under the S-wave curve divided by the area under the D-wave curve (S/D ratio) in patients with AR increased (left coronary artery flow velocity 0.66 +/- 0.39, p less than 0.05; right coronary flow velocity 0.79 +/- 0.36, p less than 0.01) as compared with the S/D ratio in patients with other heart diseases (left coronary flow velocity 0.32 +/- 0.12; right coronary artery flow velocity 0.38 +/- 0.17). There was a tendency toward a relative positive correlation between S/D ratio values and AR cineangiographic grades. Decreased S/D ratios were observed in 4 patients with aortic stenosis. It is believed that no reports exist on phasic coronary flow velocity recorded in conscious patients who had aortic valve disease.

Adult↗