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Biomedical subjects

H Inagaki

Publications and source records attributed to H Inagaki.

At least 145 records · Page 8Linked to original sources
PubMed1992

Growth-inhibitory action of an estrogen-chlorambucil conjugate (KM2210) in human breast cancer cell line MCF-7: its relation to reduction of estrogen receptor and transforming growth factor-alpha secretion.

We investigated the effects of a benzoate of an estradiol-chlorambucil conjugate (KM2210) and chlorambucil on growth, estrogen receptor, and secretion of transforming growth factor (TGF)-alpha in the hormone-dependent human breast cancer cell line MCF-7. In the presence of 10(-10)-10(-6) M KM2210, the estrogen-induced growth of MCF-7 was completely inhibited. Inhibited growth of MCF-7 treated with 10(-8) or 10(-6) M KM2210 for 4 days was not rescued by removal of the drug and the addition of estradiol. By treatment of MCF-7 with KM2210 for 4 days, estrogen receptor-binding sites were decreased at 10(-8) M and were not detected at 10(-6) M but were unaltered by 10(-8) M chlorambucil. Moreover, estrogen receptor immunoreactivity and the level of estrogen receptor mRNA were decreased through treatment with 10(-6) M KM2210 for 4 days. These suppressions occurred prior to the onset of inhibitory action on MCF-7 growth. Secretion of TGF-alpha from MCF-7 was decreased by 4 days of treatment with 10(-8) and 10(-6) M KM2210 but not with chlorambucil. The addition of exogenous TGF-alpha generally restored the growth of MCF-7 treated with 10(-8) M KM2210. We concluded that KM2210 has irreversible or at least long-standing inhibitory effect on estrogen-dependent growth of MCF-7. It is conceivable that the decrease of estrogen receptor renders the cell unable to respond to estrogen with increased TGF-alpha secretion and succeeding cell growth.

Antineoplastic Agents↗
PubMed1992

Autoradiographic localization of endothelin-1 binding sites in human colonic cancer tissue.

Endothelin-1, a potent vasoconstrictor, has been reported to stimulate mitogenesis in various types of normal and neoplastic cells and to be involved in neurotransmission. Recently, many human cancer cell lines, including those from the human colon, have been shown to produce endothelin. In this study, the occurrence of endothelin-1 binding sites was investigated in human colonic cancer tissues using in vitro autoradiography. Specific [125I]endothelin-1 binding sites were identified over tumour vessels and stromal tissues surrounding cancer cell nests. The distribution was heterogeneous, and dense silver grains were localized, especially over clusters of fibroblasts adjacent to the cancer cell nests. Endothelin binding was minimal in the cancer cells, as in the normal crypt epithelium. Quantitative analysis of the autoradiographs demonstrated high affinity (Kd = 0.50 +/- 0.06 nM; mean +/- SEM) binding sites, with a maximum binding capacity (Bmax) of 40 +/- 3.2 amol/mm2 in the cancer tissues. Our results provide evidence that specific endothelin-1 binding sites are expressed in the stromal tissues including tumour vessels, fibroblasts, and nerve fibres. Endothelin-1 may play a modulatory role in blood supply, mitogenesis, and neurotransmission in a paracrine fashion through the stromal components in human colonic cancers.

Adenocarcinoma↗
PubMed1992

Localisation of endothelin like immunoreactivity in adult and developing human gut.

The distribution of immunoreactivity for the potent vasoconstrictor endothelin-1 was studied in adult and developing human gut using antisera to endothelin-1 (1-21) and the C terminus of big endothelin-1. The coexistence of these peptides with other neuropeptides was investigated using comparative immunocytochemistry. Endothelin-1 like immunoreactivity was detected in extracts of adult (range 20-60 fmol/g wet weight) and fetal (33 fmol/g) gastrointestinal tract and was shown by chromatography to be the predominant isoform of endothelin present in both. It was localised by immunocytochemistry to ganglion cells in the submucous and myenteric plexuses and to scattered nerves, whereas big endothelin-1 like immunoreactivity was found in the submucous plexus only. Colocalisation studies showed immunoreactivity for both endothelin-1 and vasoactive intestinal peptide in the same ganglion cells of the submucous plexus. Although endothelin-1 immunoreactivity was not detected by immunocytochemistry in the fetal human gut until the 32nd week of gestation, big endothelin-1 was found as early as 11 weeks in the developing neural structures and epithelial cells. The latter were shown to be endocrine cells by their immunoreactivity for chromogranin. Our results indicate that endothelin is a neuropeptide found in adult human gut which shows transient expression in endocrine cells during development.

Adult↗
PubMed1992

Dangerous mixture of household detergents in an old-style toilet: a case report with simulation experiments of the working environment and warning of potential hazard relevant to the general environment.

A housewife cleaned toilet porcelain connected directly to a sewage storage tank with a mixture of cleaning agents; sodium hypochlorite (NaOCl) and hydrochloric acid (HCl) solutions. She complained of insomnia on the night after cleaning and suffered from severe metabolic acidosis with extremely low blood pH, PCO2 and bicarbonate values. She recovered from the acidosis after bicarbonate transfusion, plasmapheresis and plasma exchange. Permanent blindness ensued, however, from the third day after the event. These clinical symptoms suggested that the toxic substances responsible were chloramine and methyl chloride. Their generation was confirmed by in-vitro experiments, mixing NaOCl, HCl and pooled urine from normal people. In the simulation, the methyl chloride level far exceeded (100,000 ppm) the maximal allowable concentration recommended (ca 400 ppm) by the American Conference of Governmental Industrial Hygienists (ACGIH). Chloramine's toxic actions were confirmed using purified enzyme assay, and the inhibition of carbonic anhydrase and aldehyde dehydrogenase and the enhancement of superoxide dismutase activity were confirmed in neutral pH. The patient's clinical symptoms suggested that insomnia and permanent blindness seemed to be partly ascribable to chronic repetitive exposure to methyl chloride; catching a cold, drug intake and alcohol intake, in addition, precipitated the patient's visual loss. The possibility of this kind of intoxication with such a mixture of agents may lie latent in any situation where sewage or garbage are exposed to the open air.

Acidosis↗
PubMed1992

Circadian rhythm of plasma uric acid and handling stress-induced hyperuricemia in conscious cebus monkeys.

An apparent circadian rhythm of plasma uric acid and the effect of handling stress on plasma uric acid level in conscious cebus monkeys were demonstrated. The lowest level of plasma uric acid in the circadian rhythm occurred early in the morning and the highest, before bedtime at night. With experimental handling stress, the plasma uric acid level rose to much more than the maximum level of the circadian rhythm. Stress-induced hyperuricemia could be inhibited without an increase of urinary uric acid excretion by the minor tranquilizer diazepam at doses of more than 1 mg/kg, p.o. On the other hand, benzbromarone at 20 mg/kg, p.o. significantly inhibited the hyperuricemia with a hyperuricosuric effect, while probenecid at 50 mg/kg, p.o. had no effect on either the increased plasma uric acid or urinary uric acid excretion. Accordingly, it is concluded that the plasma uric acid level in conscious cebus monkeys easily fluctuates with experimental conditions and that the animals can be utilized to evaluate the hypouricemic and hyperuricosuric property of benzbromarone-like agents.

Animals↗
PubMed1992

[Interhemispheric choroidal epithelial cyst associated with partial agenesis of the corpus callosum: case report and review of the literature].

A case of interhemispheric choroidal epithelial cyst is reported. The patient is a 9-month-old female who was transadmitted to our hospital for further examination because of the enlargement of her head. She had no neurological deficits nor symptoms of increased intracranial pressure. CT scanning performed on admission showed multiple cystic lesions in the right frontoparietal interhemispheric space, whose circumference was partially enhanced with contrast medium. Metrizamide CT cisternography demonstrated no communication between the lesions and the ventricular system. The signal intensity of the cysts was higher than that of cerebrospinal fluid on both T1-weighted and T2-weighted MR images. Sagittal T1-weighted images showed partial agenesis of the corpus callosum. The surgical exploration was performed via interhemispheric approach. The cyst wall was found to be white, relatively rich in vascular components, and was removed as much as possible. The examination of the cyst fluid showed total protein levels of 1250 to 3440 mg/dl, and sugar contents of 43 to 99mg/dl. Callosal agenesis was confirmed at operation. The light microscopic examination revealed that the cyst wall was composed of a single layer of columnar or cuboidal epithelium with occasional papillary configuration and thick collagenous connective tissue. The epithelial cells contained PAS-positive granules in the cytoplasm. Electron microscopy showed numerous club-shaped microvilli with no coating materials, continuous basement membrane, tight junction, interdigitation, and multiple fenestrations of endothelium of stromal vessels. On the basis of these findings, the lesion was diagnosed as choroidal epithelial cyst. In the literature, interhemispheric choroidal epithelial cyst associated with partial callosal agenesis, confirmed ultrastructurally, has not, to out knowledge, been reported.

Agenesis of Corpus Callosum↗
PubMed1992

[Clival chordoma in an infant; case report and review of the literature].

Skull base chordoma in infants is a very rare entity in spite of its congenital origin; only 11 clinical cases can be found in the literature so far. Here we report such a case and review the literature. The case is that of a 3.5-year old boy suffering from left abducent nerve palsy for 5 months. CT scan revealed an isodense mass lesion with bone destruction involving the clivus and left petrous apex, and was homogeneously enhanced on post-contrast study. MRI disclosed the clival tumor as a long T1 and long T2 mass. Angiogram showed no tumor stain. The tumor was preoperatively diagnosed as clival chordoma, and was partially removed via left transpetrosal-transtentorial approach. The tumor was found to extend into the subdural space through Dorrello's canal and compress the abducent nerve. Histological examination with H & E, PAS, mucicarmine, and reticulin stainings led us to a diagnosis of "typical chordoma". Electron microscopy demonstrated the mitochondria-endoplasmic reticulum complexes (MERC), glycogen granules, and vacuoles in the tumor cells. Postoperative irradiation (total dose 55 Gy) was performed. At present, 30 months after the operation, no evidence of tumor regrowth nor hypothalamus-pituitary deficiency is recognizable and the patient is free from left abducent nerve palsy. It is concluded that skull base chordoma in infants should be postoperatively irradiated in an appropriate manner.

Child, Preschool↗
PubMed1991

Usefulness of QRST time-integral values of 12-lead electrocardiograms in diagnosing healed myocardial infarction complicated by left bundle branch block.

The usefulness of QRST time-integral (IQRST) values of 12-lead electrocardiograms for diagnosing a prior myocardial infarction complicated by left bundle branch block (LBBB) was determined. The study consisted of 25 patients with LBBB (11 with and 14 without myocardial infarction). The IQRST values in each lead point of 12-lead electrocardiograms were calculated. Data from 607 normal subjects were used as controls and mean +/- 2 standard deviations was regarded as the normal range. The following parameters were derived: number of leads less than the normal range of IQRST values (nQRST) and sum of the differences between the normal mean IQRST value and IQRST value of a given patient in leads where this value was less than the normal range (sigma QRST). The criteria of nQRST (12-lead) greater than or equal to 5 and sigma QRST (12-lead) greater than or equal to 500 microV in 12-lead electrocardiograms were selected on a relative cumulative frequency distribution and demonstrated the presence of a myocardial infarction in LBBB with a sensitivity of 82% and a specificity of 100% for each. With regard to the localization of the myocardial infarction, the criterion of sigma QRST (V1-6) greater than or equal to 300 microV in leads V1-6 of 12-lead electrocardiograms demonstrated the presence of an anterior myocardial infarction in the LBBB with a sensitivity of 88% and a specificity of 77%. It was difficult to localize an inferior myocardial infarction in patients with LBBB by using IQRST values of inferior leads.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Parental origin and mechanism of formation of polysomy X: an XXXXX case and four XXXXY cases determined with RFLPs.

The parental origin and mechanism of formation of polysomy X were studied in five cases (one case of 49,XXXXX; four cases of 49,XXXXY), using various X-linked restriction fragment length polymorphisms as genetic markers. Segregation and densitometric analyses on the polymorphic DNA fragments revealed that, in all five cases, the additional X chromosomes are of maternal origin and the mechanism of formation is most probably a result of three non-disjunctions during maternal meiotic divisions: once at the first meiosis and simultaneously twice at the second meiosis. The identical origin and the identical mechanism of formation among the five cases are unlikely to be coincidental and suggest a common cause in the mothers of the five cases.

Abnormalities, Multiple↗
PubMed1991

Localization of endothelinlike immunoreactivity and endothelin binding sites in human colon.

The potent vasoconstrictor endothelin was originally isolated from vascular endothelial cells but has since been found in several other tissues. The aim of this study was to establish whether endothelinlike immunoreactivity occurs in human enteric nerves and to identify endothelin binding sites using immunocytochemical and in vitro autoradiographic techniques. Endothelinlike immunoreactivity was localized to nerve bundles throughout the colon and to most of the ganglion cells of the two major plexuses, many of which costored vasoactive intestinal polypeptide. High-affinity (dissociation constant = 0.35 +/- 0.014 nmol/L; mean +/- SEM) binding sites for endothelin 1, with an apparent binding capacity of 92 +/- 6.3 amol/mm2 (mean +/- SEM), were demonstrated in the myenteric plexus, with less dense binding being found in the submucous plexus, mucosa, muscle layers, and blood vessel walls. Competition data suggested two populations of binding sites, both showing high affinities for endothelins 1 and 2, vasoactive intestinal constrictor, and sarafatoxin b but differentiated by their affinity for endothelin 3 and sarafatoxin c. This study provides evidence that endothelin is a neuropeptide in the human intestine with binding sites on neural plexuses and mucosa, suggesting a role in the modulation of intestinal motility and secretion.

Adult↗
PubMed1991

Localization of endothelin-1 and its binding sites to the nervous system of the human colon.

Endothelin-1 (ET-1) has been reported to possess a wide variety of biological activities, including neurotransmission. Our aim was to demonstrate ET-like immunoreactivity (ET-LI) and its binding sites in human enteric nervous system using immunohistochemistry and in vitro autoradiography. ET-LI was displayed in nerve bundles and most of the ganglion cells in both myenteric and submucous plexuses, many of which costored VIP. [125I]ET-1 binding sites were identified, especially to plexuses, mucosa, and blood vessels. High-affinity (Kd = 0.35 +/- 0.014 nM; mean +/- SEM) binding sites, with a maximum binding capacity (Bmax) of 92 +/- 6.3 amol/mm2, were demonstrated in the myenteric plexus. This study provides evidence that ET-1 is a neuropeptide in the human colon with binding sites on neural plexuses and mucosa, indicating a possible role in the modulation of motility and secretion in the human intestine.

Autoradiography↗
PubMed1991

[The expression of the blood related antigens in intestinal metaplasia of the stomach in gastric cancer].

The monoclonal antibodies detecting blood group related antigens of the Lewis systems have been used to define the immunoanatomic distribution of these antigens within the normal gastric mucosa and in gastric cancer tissues. In this study we analysed the presence of these antigens in histologically intestinal metaplasia of the stomach by the immunoperoxidase method. In normal gastric mucosa, Lewisb was distinctly expressed in normal foveolar epithelia and Lewisa was present in foveolar epithelia in half of the cases. Lewisx and Lewisy were detected in deep gastric glands. In intestinal metaplasia, more pronounced expression of Lewisa and decreased expression of Lewisb were observed. Lewisx and Lewisy were absent in most specimens of intestinal metaplasia. These pattern of expression of Lewis antigens in intestinal metaplasia were very similar to those observed in well and moderately differentiated adenocarcinomas of the stomach. These results indicate that well and moderately differentiated adenocarcinomas of the stomach have very similar character with the intestinal metaplasia in terms of the Lewis blood group antigen expression.

Adenocarcinoma↗
PubMed1990

Inhibition of estradiol uptake and transforming growth factor alpha secretion in human breast cancer cell line MCF-7 by an alkyl-lysophospholipid.

We investigated the effect of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), an alkyl-lysophospholipid, on the uptake of estrogen, the secretion of transforming growth factor (TGF) alpha and the content of progesterone receptors (PRs) in the hormone-dependent breast cancer cell line, MCF-7. The uptake of labeled estradiol by MCF-7 was dose dependently decreased by 12 h pretreatment with 10-25 micrograms/ml ET-18-OCH3, and this suppression occurred prior to the onset of the inhibitory action of ET-18-OCH3 on MCF-7 growth. Scatchard analysis demonstrated that ET-18-OCH3 reduced the number of estrogen receptors in MCF-7 without affecting their affinity. Both the secretion of TGF-alpha from MCF-7 into the conditioned medium and the PR content of MCF-7 were decreased by 48 h treatment with 10 micrograms/ml ET-18-OCH3. The estradiol uptake, the TGF-alpha secretion, and the PR content were not affected by platelet-activating factor, lyso-PAF, and palmitoyl-lysophosphatidylcholine, all at 10 micrograms/ml. These results suggest that the reduction of estrogen receptor level induced by ET-18-OCH3 resulted in decreases in both the secretion of TGF-alpha and the content of PR in MCF-7, and these effects are specific to ET-18-OCH3. We concluded that these effects of ET-18-OCH3 may lead, at least partly, to its antitumor action in hormone-dependent breast cancer cell lines.

Antineoplastic Agents↗
PubMed1990

Detection of transforming growth factor alpha in human urine and plasma.

A sensitive enzyme-linked immunosorbent assay (ELISA) system for human transforming growth factor alpha (TGF alpha) was developed in combination with polyclonal and monoclonal antibodies. Employing this assay system, we detected TGF alpha like activity in normal human plasma as well as in cancer patients' urine and plasma. These TGF alpha were analyzed by chromatography, immunoreactivity, and EGF-TGF alpha receptor binding assay and found to be identical to authentic human TGF alpha. The presence of TGF alpha circulating in normal adult plasma suggests a new role of TGF alpha in the human body.

Biomarkers↗
PubMed1990

A new sandwich enzyme-linked immunosorbent assay (ELISA) for transforming growth factor alpha (TGF alpha) based upon conformational modification by antibody binding.

A sandwich-type enzyme-linked immunosorbent assay (ELISA) for human TGF alpha was established utilizing monoclonal and polyclonal anti-synthetic human TGF alpha antibodies with defined epitopes. A polyclonal antibody which was raised in a rabbit and affinity purified by C terminal peptide (hTGF alpha (34-50)) recognized both intact and denatured human TGF alpha. Murine monoclonal antibodies isolated bound only to the denatured form of TGF alpha at the second loop (hTGF alpha (16-33)). However, the rabbit antibody was found to induce a conformation change of intact TGF alpha and the resultant immunocomplex was recognized by monoclonal antibodies. By virtue of this property, the ELISA could detect both native and denatured TGF alpha with the same efficiency with a detection limit of 0.1 ng/ml. Human EGF did not interfere with the ELISA. Production of TGF alpha in several transformed human cell lines was quantitatively examined. Some cell lines were found to secrete TGF alpha, but the production rate was very low, except one melanoma, suggesting that TGF alpha may function only locally in a very limited area in vivo.

Animals↗
PubMed1990

Prediction of left ventricular function during supine bicycle ergometer exercise in angina-free patients with old myocardial infarction.

We investigated whether or not left ventricular function during dynamic exercise in angina-free patients with old myocardial infarction could be estimated using resting left ventricular function and noninvasive parameters determined during exercise. We studied 70 patients with old myocardial infarction by measuring hemodynamic parameters during supine multistage bicycle ergometer exercise. Coronary arteriography and left ventriculography were performed: then the left ventricular ejection fraction and left ventricular end-diastolic volume were measured. The parametric changes (delta) between rest and peak exercise were determined. Significant positive correlations were observed between cardiac index (CI) at rest and at peak exercise (r = 0.62, p less than 0.001), as well as between pulmonary artery wedge pressure (PAWP) at rest and at peak exercise (r = 0.72, p less than 0.001). Multiple regression analysis indicated that CI and PAWP at peak exercise as dependent variables were best described by the equations: CI at peak exercise = 1.074 [CIrest] +0.031 [delta HR] + 0.004 [ExD] + 0.018 [LVEF] - 1.560 (r = 0.79, p less than 0.001), PAWP at peak exercise = 0.994 [PAWPrest] - 0.181 [LVEF] + 0.203 [delta DBP] -0.076 [delta HR] -21.488 (r = 0.80, p less than 0.001). These data suggested that CI and PAWP during dynamic exercise in angina-free patients with old myocardial infarction could be predicted using noninvasive parameters, such as increments of blood pressure and heart rate as well as exercise duration, together with data on resting left ventricular function, such as resting CI, resting PAWP, and resting left ventricular ejection fraction (LVEF).

Adult↗