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Biomedical subjects

I Shimizu

Publications and source records attributed to I Shimizu.

At least 109 records · Page 6Linked to original sources
PubMed1989

[Evaluation of the internal carotid artery blood flow velocity waveforms using continuous-wave Doppler ultrasound in pregnant women].

The internal carotid artery blood flow velocity waveforms were measured with continuous-wave Doppler ultrasound in 17 normal nonpregnant and 50 pregnant women. 1) The measurement of the blood flow velocities in the pregnant women revealed a characteristic pattern. That is, in the women in the early pregnant stage (less than 16 weeks' gestation, n = 13), the velocity was lower than that of nonpregnant women. In the middle pregnant stage (16 to 27 weeks' gestation, n = 18), the velocity became higher than in the early stage and in the late stage (equal to and more than 28 weeks' gestation, n = 19), it again became slower. 2) The initial systolic peak blood velocity (S1), end-diastolic blood velocity (d), time averaged maximal blood velocity (M), Pourcelot ratio (PR), systolic-diastolic ratio (S/D) and pulsatility index (PI) were calculated and did not show laterality in any group. 3) PR, S/D and PI of the women in the early stages of pregnancy were higher than those of nonpregnant women, indicating that the cerebral vascular resistance became higher in early pregnancy. This technique presented the possibility of the assessment of the cerebral blood circulation in pregnant women.

Adult↗
PubMed1988

Preliminary report on the use of danazol in the treatment of endometrial adenomatous hyperplasia.

Since the authors recently reported that danazol inhibits the growth of human endometrial cancer cells in vitro, a clinical trial was initiated to examine whether danazol can regress adenomatous hyperplasia, a precursor of endometrial adenocarcinoma. Danazol was used for 3 months in the treatment of five patients with a history of hypermenorrhea and irregular uterine bleeding. Within a 9-month follow-up period, all patients were symptom-free, and none of the specimens obtained by endometrial biopsy showed the presence of adenomatous hyperplasia. These findings suggest that danazol has a potential application in the treatment of patients with endometrial adenomatous hyperplasia. A possible mechanism of action of the compound in adenomatous hyperplasia is also discussed.

Adenoma↗
PubMed1988

Onset and development of intersegmental projections in the chick embryo spinal cord.

The ontogeny of intersegmental (propriospinal) projections was studied in the chick embryo spinal cord between embryonic day 2.5 and day 6. Our goals were 1) to determine the earliest projections of intersegmental interneurons between specific spinal regions and to establish the cell types involved; and 2) to follow the ontogeny of these projections during the early formative stages of spinal cord development. Studies were carried out in vitro by using an isolated spinal cord/brainstem preparation. Horseradish peroxidase injections were made either uni- or bilaterally at various levels of the spinal cord along the rostrocaudal axis of the embryo. HRP histochemistry was done on Vibratome sections with diaminobenzidine as the chromogen. Following unilateral injections at day 2.5, labelled commissural interneurons were found contralaterally and were confined to the injected segment. Subsequently, labelled cells were found progressively further away from the injected segment. By day 4.5 reciprocal projections extended between lumbar and brachial regions. Interneurons with intersegmental axonal projections were often undifferentiated, consisting of primitive unipolar or bipolar cells with little, if any, dendritic development. In some cases migrating interneurons could be retrogradely labelled from two or three segments away from the location of their translocating cell body. Anterograde Golgi-like labelling of early undifferentiated cells revealed growing axons, axonal terminals, and growth cones. Five or six reasonably distinct classes of intersegmental interneurons were identified based on their location, axonal projections, and morphology of dendritic arbors. These appeared to be segmentally and bilaterally arranged along the rostrocaudal axis of the spinal cord. The axons of some of these types of interneurons exhibited preferences in their longitudinal projections within the ventral and ventrolateral marginal zone at the very onset of pathway formation. From the present observations it can be concluded that intersegmental connectivity precedes the development of ascending and descending supraspinal, as well as primary afferent connections in the chick embryo spinal cord.

Animals↗
PubMed1988

4-Hydroxytamoxifen binds to estrogen receptors and inhibits the growth of human endometrial cancer cells in vitro.

Effects of 4-hydroxytamoxifen, a major metabolite of tamoxifen, on the proliferation of cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were investigated in primary culture. Competitive binding studies showed that 4-hydroxytamoxifen effectively binds to cytoplasmic estrogen receptors (ER) in uterine adenocarcinomas. Of 20 endometrial adenocarcinomas examined, five tumors were successfully grown in primary cell culture. The addition of 4-hydroxytamoxifen (1 nmol/l to 1 mumol/l) in a medium supplemented with estrogen-free serum resulted in a dose-dependent inhibition of the growth of cancer cells in two tumors having ER. However, 4-hydroxytamoxifen did not affect the growth in the culture system of the remaining three tumors, in which ER were absent in two tumors but were present in one. These results strongly suggest that tamoxifen has a direct growth-inhibitory effect on human endometrial adenocarcinoma possibly through ER in the tumor.

Adenocarcinoma↗
PubMed1988

Developmental changes in density and distribution of serotoninergic fibers in the chick spinal cord.

Developmental changes of serotoninergic innervation in the chick spinal cord (third lumbosacral segment) were examined with an immunohistochemical technique using an antiserum to serotonin. In the 1-day-old hatched chick, serotoninergic fibers were located in laminae I, II, VII, IX, and X. A large number of serotonin-positive fibers and terminals were found around somal profiles of large neurons and in the neuropil of the medial and lateral parts of the lateral motor column (LMC). In the 1-week-old chick, the density of serotoninergic fibers was greatly increased in the posterior columns, and serotoninergic fibers were most densely aggregated in the dorsolateral part of the LMC. In the 2-week-old chick, a considerable decrease in the density of serotoninergic fibers was observed in the lateral funiculus and the gray matter (laminae I, II, VII, IX, and X). In the LMC, serotonin-positive fibers and terminals were largely absent from the neuropil, but were found preferentially around the somal profiles of large neurons. Between 1 and 2 weeks after hatching the density of varicosities and terminals in the neuropil of the dorsolateral and medial parts of the LMC decreased by 33% and 56%, respectively. In the 3-month-old chick, the density of serotoninergic fibers in laminae I, II, V, VII, and X had increased compared to younger ages. Serotonin-positive fibers were not evenly distributed in the LMC of the adult chicken; rather, they were densely aggregated around the soma and proximal dendrites of motoneurons in the dorsolateral LMC. Many neuronal soma in the medial and intermediate regions of the LMC lacked serotoninergic fibers.

Animals↗
PubMed1988

Effects of bile salts on plasma concentration of beta-endorphin-like immunoreactivity in men.

The effects of bile salts on the release of beta-endorphin-like immunoreactivity (beta-END-LI) were investigated in men using a specific radioimmunoassay developed by the authors. Plasma beta-END-LI was determined after extraction by the acid-acetone method (recovery: 73 +/- 5%). Oral administration of 400 mg of sodium taurocholate caused a rise in plasma beta-END-LI from 9.9 +/- 0.5 pmol/liter to 21.3 +/- 1.2 pmol/liter after 30 min and 18.1 +/- 0.5 pmol/liter after 60 min, with return to the initial value after 90 min. Oral administration of chenodeoxycholic acid (CDCA) also increased plasma beta-END-LI from a basal level of 8.4 +/- 0.7 pmol/liter to 18.7 +/- 0.8 pmol/liter after 30 min. Oral administration of ursodeoxycholic acid (UDCA) increased plasma beta-END-LI from 7.3 +/- 0.3 pmol/liter to 30.6 +/- 0.2 pmol/liter after 30 min. In gel chromatography, the beta-END-LI released after UDCA administration separated into two components, which eluted in the same positions as human beta-lipotropin and human beta-endorphin, respectively. These results suggested that bile salts may participate the release of beta-END-LI.

Administration, Oral↗
PubMed1988

RU486, a progestin antagonist, binds to progesterone receptors in a human endometrial cancer cell line and reverses the growth inhibition by progestins.

The human endometrial cancer cell line, IK-90 cells, contains estrogen-independent progesterone receptors (PR) and is progestin sensitive. Accumulation of glycogen in the cytoplasm of IK-90 cells as well as growth inhibition of the cells in response to progestins are observed. In the present study, the effects of RU486, a progestin antagonist, on IK-90 cells were investigated in a serum-supplemented medium. Scatchard plot analysis of cytoplasmic binding data in the cells revealed a high affinity binding site for RU486 (Kd, 2.6 nM) with maximum binding sites of 169 fmol/mg protein. However, the binding ability to DNA-cellulose of heat activated [3H]RU486-PR complexes was lower when compared with that of the progestin agonist [3H]R5020-PR complexes, suggesting a decrease in progestin activity of RU486 in IK-90 cells. The addition of 1 microM RU486 to culture medium produced periodic acid-Schiff-positive granules in the cytoplasm of the cells. On the other hand, RU486 (1 nM-1 microM) did not significantly inhibit the growth of cells. However, RU486 (0.1-1 microM) totally prevented the growth-inhibitory effect of R5020 (0.1-1 microM) on IK-90 cells. In conclusion, RU486, an antiprogestin, had a dual activity both a progestin antagonist and weak agonist in human endometrial cancer cells, which was not mediated through the estrogen receptor system.

Binding, Competitive↗
PubMed1988

Inhibitory effects of danazol and medroxyprogesterone acetate on [3H]thymidine incorporation in human endometrial cancer cells.

Effects of medroxyprogesterone acetate (MPA) and danazol (1 nM-10 microM) on cultured cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were simultaneously investigated. Of twenty-four endometrial adenocarcinomas examined, five tumors were successfully maintained in primary cell culture. The addition of MPA as well as danazol in culture of cells from the five tumors resulted in a significant inhibition of [3H]thymidine incorporation in cancer cells from three tumors having progesterone receptors (PR). The minimum effective concentrations of MPA and danazol for the inhibition of [3H]thymidine incorporation were found to be 10 and 100 nM, respectively. The difference in effective concentration could be explained by a higher affinity of MPA to PR than that of danazol in cancer cells. On the other hand, neither danazol nor MPA affected [3H]thymidine incorporation in cultured cells from the remaining two tumors, in which PR was absent in one but present in the other. These findings, together with our previous findings that danazol inhibited the growth of a human endometrial cancer cell line with PR, suggest that a growth-inhibitory effect of danazol on human endometrial cancer cells is mediated through PR in the cells.

Adenocarcinoma↗
PubMed1988

Cytochemical demonstration of guanase in human liver using yellow tetrazolium.

Histochemical studies of human guanase (guanine deaminase) have seldom been undertaken, in part because of technical difficulties which result in heavy background staining. We reported a modified procedure for histochemical demonstration of guanase in human tissues involving hydrolytic deamination of the substrate guanine to xanthine via guanase, and then oxidation of xanthine to uric acid, with concomitant reduction of nitrotetrazolium blue (NBT). In this report, we describe a modification of this method for cytochemical demonstration of guanase at the fine structural level using yellow tetrazolium in place of NBT for determination of the intracellular distribution of guanase in human hepatocytes. In the hepatocytes, the reaction products were seen to be concentrated in the nucleus, in mitochondria, cisternae of the smooth and/or rough-surfaced endoplasmic reticulum, and lysosomes. The precise locations of the reaction product in the cisternae of the nuclear envelope, chromosomes, and nucleus could not be determined. However, the reaction products in the mitochondria were clearly seen to be located in the spaces of cristae. This information of the intracellular distribution of guanase in normal hepatocytes will be useful in determining the physiological role of this enzyme and in further studies on diseased hepatocytes including those in non-A non-B hepatitis.

Aminohydrolases↗
PubMed1987

A large molecular form of glucagon-like peptide-1 (GLP-1) immunoreactivity is co-released with glucagon from pancreas by arginine in normal subjects.

Plasma immunoreactivities of glucagon-like peptide-1 (GLP-1IR) in normal subjects were measured with a specific radioimmunoassay during the arginine tolerance test. Plasma GLP-1IR after arginine infusion showed a 3-fold increase in parallel to plasma glucagon immunoreactivity and plasma glucagon-like immunoreactivity, measured with a glucagon C-terminal specific antiserum (OAL 123) and an N-terminal and/or central region specific glucagon antiserum (OAL 196), respectively. This finding suggested that the increased immunoreactivities of GLP-1 as well as that of glucagon were of pancreatic origin. Upon gel chromatography, plasma at the basal state showed three GLP-1 immunoreactive peaks, eluted in the position of void volume, synthetic GLP-1(72-108), and a smaller molecular fraction. Gel chromatography of plasma after an arginine load showed an additional peak (Mr 13,000-15,000) with little change in other GLP-1 immunoreactive peaks. This large molecular form of GLP-1IR was also shown to exist in the human pancreatic extract. Moreover, the free GLP-1 concentrations in plasma before and after an arginine load were shown to be about equal by reverse phase HPLC. These data suggested that in normal subjects arginine stimulation co-releases GLP-1IR, predominantly large molecular form, with glucogen from the pancreas.

Adult↗
PubMed1987

Growth inhibition by progestins in a human endometrial cancer cell line with estrogen-independent progesterone receptors.

The presence of estrogen-independent progesterone receptors (PgR) was demonstrated in a subline of a human endometrial cancer cell line, Ishikawa cells, although the original Ishikawa cells contained estrogen-inducible PgR. Scatchard plot analysis of cytoplasmic binding data in our subline (IK-90) revealed a high affinity binding site for R5020 (Kd, 1.0 nM) with maximum binding sites of 158 fmol/mg protein. Competition experiments showed a binding specificity similar to that of typical PgR. By low-salt sucrose gradient centrifugation, radioactive 8S and 4S peaks were found. The addition of 1 microM progesterone in culture medium resulted in a rapid nuclear translocation of cytoplasmic PgR. In contrast to the original cells, estrogen receptors could not be detected in IK-90 cells, and an addition of 17 beta-estradiol (10 nM) to culture medium failed to increase PgR. Accumulation of glycogen in cytoplasm of IK-90 cells in response to R5020 (0.1-1 microM) was observed by periodic acid-Schiff staining. The addition of R5020 to culture medium (0.1-1 microM) also caused a marked decrease in the growth of IK-90 cells, whereas the other steroids including 17 beta-estradiol, tamoxifen, testosterone, and cortisol had no significant effects. These results demonstrate for the first time the presence of a progestin-responsive human endometrial cancer cell line that contains estrogen-independent functional PgR. IK-90 cells appear to be an ideal model for studying the mechanism of the antiproliferative effect of progestin on endometrial cancer cells.

Cell Division↗
PubMed1987

Effect of the enteroinsular axis on both the A- and B-cell response to arginine after oral glucose in man.

Studies were made on the effect of the enteroinsular axis on amino acid-induced insulin and glucagon secretion during hyperglycaemia in man. The responses of plasma immunoreactive insulin, C-peptide, and immunoreactive glucagon to arginine infusion were investigated in nine healthy subjects after induction of hyperglycaemia by an oral glucose load and by intravenous glucose infusion to produce similar glucose concentrations in the arterialised blood. The plasma immunoreactive insulin and C-peptide levels increased to higher levels after an oral glucose load than after an intravenous infusion of glucose. The incremental areas under the immunoreactive insulin and C-peptide curves during arginine infusion were significantly greater (p less than 0.01) after oral than after intravenous glucose administration. The plasma immunoreactive glucagon level was suppressed equally after oral and intravenous glucose loads. However, during subsequent arginine infusion, the plasma immunoreactive glucagon level rose more in the presence of hyperglycaemia induced by oral than intravenous glucose. The incremental area under the plasma immunoreactive glucagon curve during arginine infusion was 1.6-fold greater after glucose ingestion than after intravenous glucose infusion. These results suggest that the enteroinsular axis has a stimulatory effect on the responses of pancreatic A and B cells to arginine after oral glucose administration.

Administration, Oral↗
PubMed1987

Effects of gut hormones on bile acid uptake and release in cultured rat hepatocytes.

In cultured rat hepatocytes, the effects of gut hormones on bile acid uptake and release were studied. It was found that cultured hepatocytes continued to secrete bile acids into the culture medium and incorporated them effectively as a function of incubation time. Gut hormones such as secretin, glucagon, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), gastric inhibitory polypeptide (GIP), tetragastrin, cholecystokinin-octapeptide (CCK-8), pancreatic polypeptide (PP), neurotensin substance P, beta-endorphin (beta-End), methionine-enkephalin (Met-enk), motilin, bombesin and somatostatin (SS) had no effect on bile acid uptake by cultured hepatocytes. In bile acid release studies, only secretin caused a dose-dependent stimulation of bile acid release, while other gut hormones had no effect on bile acid release into medium. These results indicate that secretin acts directly on cultured rat hepatocytes and/or bile canaliculi, besides its effect on the bile duct, and influences bile acid metabolism.

Animals↗
PubMed1987

Growth inhibition by danazol in a human endometrial cancer cell line with estrogen-independent progesterone receptors.

Since we recently found that danazol, an isoxazol derivative of ethinyltestosterone, has a growth-inhibitory effect on human endometrial cancer cells in primary culture, the effects of danazol on a human endometrial cancer cell line (IK-90 cells), which contains estrogen-independent progesterone receptors (PR), were investigated in the present study. The addition of danazol (1 nM-1 microM) in culture medium caused a decrease in the growth of IK-90 cells in a dose-dependent manner. Competitive binding studies showed that danazol effectively binds to PR in IK-90 cells, and the binding affinity for PR was estimated to be 6.0% of that of R5020. The addition of 1 microM danazol in culture medium resulted in a rapid and significant increase in nuclear PR with a concomitant decrease in cytoplasmic PR in the cells. These findings suggest that danazol has a growth-inhibitory effect on human endometrial adenocarcinoma cells directly through PR system in the cells.

Binding, Competitive↗
PubMed1987

Roles of antiestrogen binding sites in human endometrial cancer cells.

Estrogen-noncompatible antiestrogen binding sites (AEBS) as well as estrogen receptors (ER), and the growth-inhibitory effect of tamoxifen were investigated in two human endometrial cancer cell lines, IK-90 and HEC-IA cells. IK-90 cells contained specific AEBS, but no ER was found in these cells. Scatchard plot analysis of AEBS in 12,000 g supernatant from IK-90 cells showed a high affinity binding site for tamoxifen (Kd:5.6 +/- 1.0 nM) with the maximum binding site of 457 +/- 47 fmol/mg protein. However, no measurable ER or AEBS was found in HEC-IA cells. The effect of tamoxifen on the growth of cells was found to be identical in both cell lines; the addition of 10 microM tamoxifen to culture medium was cytocidal whereas tamoxifen at lower concentrations (1 nM-1 microM) did not significantly affect the growth of both IK-90 and HEC-IA cells. These results demonstrate for the first time the presence of AEBS in human endometrial cancer cells. The present results also suggest that AEBS does not play a fundamental role in mediating the growth-inhibitory effect of tamoxifen in endometrial cancer cells.

Adenocarcinoma↗
PubMed1987

Identification and localization of glucagon-like peptide-1 and its receptor in rat brain.

The existence and distribution of glucagon-like peptide-1 (GLP-1) and its receptor in rat brain in relation to that of glucagon were examined. The concentration of GLP-1 immunoreactivity (GLP-1-IR), measured by a specific and sensitive RIA established in this study with anti GLP-1 serum (LMT-01), was found to be highest in the thalamus-hypothalamus, followed by the medulla oblongata. The distribution of glucagon-like immunoreactivity was similar to that of GLP-1-IR. However, appreciable glucagon immunoreactivity was detected only in the thalamus-hypothalamus. Gel filtration analysis showed the presence of GLP-1-IR of various molecular weights in the extract of thalamus-hypothalamus including that eluted at the same position as synthetic GLP-1 (1-37); moreover, HPLC analysis also confirmed the presence of GLP-1-IR, eluted at the exact position as synthetic GLP-1 (1-37). The distribution of receptors for GLP-1 corresponded with that of GLP-1-IR in the rat brain, except in the pituitary gland. The distribution of these receptors was also similar to that of glucagon receptors. The thalamus-hypothalamus, pituitary gland, and medulla oblongata were rich in GLP-1 and glucagon-binding sites. The binding affinities of GLP-1 and glucagon were in the nanomolar range [disocciation constant Kd approximately equal to 4 nM]. The presence of specific, high affinity receptors for GLP-1 was confirmed by demonstrating that GLP-1 stimulated cAMP formation in the thalamus-hypothalamus and the pituitary gland. The concentration of GLP-1 required for half-maximal stimulation of cAMP formation in these regions was about 1 nM. These results suggest that GLP-1 may be synthesized in certain parts of the brain and play a role as a neurosignal transmitter.

Animals↗