PubMed Health⌕ Search

Biomedical subjects

K Okamura

Publications and source records attributed to K Okamura.

At least 19 recordsLinked to original sources
PubMed1992

Induction of human microvascular endothelial tubular morphogenesis by human keratinocytes: involvement of transforming growth factor-alpha.

Transforming growth factor-alpha(TGF-alpha), homologous to epidermal growth factor(EGF), is closely involved in hyperproliferation of human keratinocytes. Psoriasis is a common hyperproliferative skin disease characterized by hyperproliferation of keratinocytes and abnormal development of dermal capillary networks. In this study, we have examined whether keratinocytes could enhance angiogenesis. TGF-alpha or EGF efficiently stimulated formation of tubular-like structures of human omental microvascular endothelial(HOME) cells in type I collagen gels. Human keratinocytes produced TGF-alpha. To examine whether co-cultured keratinocytes could induce tubulogenesis of HOME cells in collagen gel, we have developed a co-culture system with human keratinocytes. Surprisingly, there appeared new development of many tubular-like structures of HOME cells in collagen gels when co-cultured with keratinocytes. This keratinocytes-dependent tubulogenesis was almost completely blocked when anti-TGF-alpha-antibody was present. The TGF-alpha molecules derived from keratinocytes appeared to enhance tubulogenesis of human microvascular endothelial cells. We propose the hypothesis that secretory TGF-alpha from human keratinocytes may promote an autocrine loop to proliferate the skin keratinocytes and also a paracrine loop to induce the skin angiogenesis.

Blotting, Northern↗
PubMed1992

A model system for tumor angiogenesis: involvement of transforming growth factor-alpha in tube formation of human microvascular endothelial cells induced by esophageal cancer cells.

Tumor growth is dependent on angiogenesis, which is thought to be mediated through growth factors, such as transforming growth factor-alpha (TGF-alpha) and -beta (TGF-beta), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), produced by tumor cells. We have developed a model system for tumor angiogenesis in vitro: tube formation of human omentum microvascular endothelial (HOME) cells in type I collagen gels when these cells are co-cultured with tumor cells. Exogenously added TGF-alpha induced tube formation of HOME cells in collagen gel. In contrast, TGF-beta inhibited the TGF-alpha-induced tube formation of endothelial cells. We investigated whether tube formation could be induced in HOME cells in collagen gel when the HOME cells were co-cultured with three esophageal cancer cell lines, TE1, TE2, and TE5. TE1 and TE2 cells expressed both TGF-alpha and TGF-beta mRNA, but the level of TGF-alpha mRNA in TE2 was found to be much lower than in TE1 cells. TE5 did not express either TGF-alpha or TGF-beta. The tube formation of HOME cell was induced when they were co-cultured with TE1 cells, while both TE2 and TE5 cell lines induced tube formation at much lower rates than TE1. TE1-induced tube formation of HOME cells was specifically blocked by co-administration of anti-TGF-alpha-antibody, but not by anti-bFGF-antibody. The present study suggests that, in our model system, esophageal tumor angiogenesis is partly controlled by TGF-alpha, possibly through a paracrine pathway.

Blotting, Northern↗
PubMed1992

Induction of low density lipoprotein receptor and a transcription factor SP-1 by tumor necrosis factor in human microvascular endothelial cells.

We have previously reported that tumor necrosis factor-alpha (TNF-alpha) enhances expression of interleukin-6, collagenase, plasminogen activator inhibitor-1, and basic fibroblast growth factor genes in human omental microvascular endothelial (HOME) cells in culture. In this study, we found that treatment of HOME cells with TNF-alpha or interleukin-1 (IL-1) caused enhanced expression of low density lipoprotein (LDL) receptor. A few-fold increase in both LDL binding activity and the receptor mRNA levels was observed when HOME cells were treated with either TNF-alpha or IL-1. Northern blot analysis showed that cellular expression of LDL receptor gene was significantly increased 12-24 h after exposure to TNF-alpha. No significant changes in the life-span of LDL receptor mRNA were observed in untreated and TNF-alpha-treated cells. Scatchard analysis showed an increased receptor number for LDL in TNF-alpha-treated cells. Parallel to increased LDL binding activity, internalization and degradation of LDL were also increased in HOME cells treated with TNF-alpha or IL-1. TNF-alpha-induced enhancement of LDL receptor gene expression was not observed when cycloheximide was present. Cellular mRNA level of SP-1 gene was increased about 3-4-fold at 12 h after treatment with TNF-alpha. Nuclear run-on assays showed increased transcription of LDL receptor gene as well as SP-1 gene by TNF-alpha. Gel retardation assay with the SP-1 consensus fragment showed that SP-1 binding activity was increased about 4-5-fold 12-24 h after treatment with TNF-alpha. NF-kB binding activity was also dramatically increased, but there is no NF-kB motif on the promoter for LDL receptor gene. The induction of LDL receptor by TNF might be mediated through a transcription factor, SP-1.

Base Sequence↗
PubMed1992

Synthesis and antiulcer activity of N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas: histamine H2-receptor antagonists with a potent mucosal protective activity.

As an aim toward developing new antiulcer agents, new N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas were synthesized and evaluated for histamine H2-receptor antagonistic, gastric antisecretory, and gastric mucosal protective activities. A QSAR study showed that the most favorable N-substituents were electron-donating straight-chain alkyl groups of short length such as ethyl group from the viewpoint of dual action, i.e., gastric antisecretory and mucosal protective actions. Among the ureas studied, compounds 4, 5, and 8-10 were selected as candidates for further study.

Animals↗
PubMed1992

Decreased response to epidermal growth factor during cellular senescence in cultured human microvascular endothelial cells.

We have previously demonstrated that epidermal growth factor (EGF) induces cell migration, tissue-type plasminogen activator synthesis, as well as tubular formation in microvascular endothelial cells from human omental tissue. In this study, we compared the responsiveness to EGF of late passaged (senescent) human omental microvascular endothelial (HOME) cells with that of early passaged (young) HOME cells. We have employed HOME cells derived from surgically resected omental samples from 14 patients. EGF-stimulated cell migration significantly more in the young cells than in the senescent cells during serial cultivation (aging) in vitro. Scatchard analysis demonstrated that the number for both high and low affinity receptors for EGF in HOME cells was decreased dramatically during serial cultivation. The expression of EGF receptor mRNA was also decreased in the senescent HOME cells. Treatment of HOME cells with EGF significantly increased cellular mRNA levels of tissue-type plasminogen activator, and two protooncogenes, c-fos and c-myc, in young HOME cells, but not in senescent HOME cells. Thus HOME cells aged in vitro show a decreased responsiveness to EGF, resulting in decreased migration of human endothelial cells. The serial cultivation of human endothelial cells in vitro may downregulate EGF receptor and decrease responsiveness to exogenous EGF, a potent angiogenic factor.

Blotting, Northern↗
PubMed1992

The outcome of pregnancy and prenatal chromosomal diagnosis of fetuses in couples including a translocation carrier.

In order to evaluate the relation between chromosomal translocation and the outcome of pregnancy, 50 couples were examined. Subjects consisted of 35 couples that included a reciprocal translocation carrier; 13 included a Robertsonian translocation carrier and 2 included a carrier of a mosaic reciprocal translocation. The reasons for performing chromosomal examinations were mainly infertility and abnormality of neonates. The rates of miscarriages and neonatal abnormalities in prior pregnancies were significantly higher than the birth rate of morphologically normal newborns. The presence of a translocation is closely related to reproductive failure because of the chromosomal imbalance. However, prenatal chromosomal examination after the 15th gestational week in subsequent pregnancies revealed that almost half of the fetuses showed normal karyotypes and only 12.8 per cent of the fetuses showed a chromosomal imbalance. Many chromosomally imbalanced fetuses are spontaneously aborted before amniocentesis. The risk of chromosomal imbalance is relatively low in prenatal diagnosis, but partial trisomies of small rearrangements tend to be preserved.

Adult↗
PubMed1992

Change in electrocardiogram T-wave amplitude during umbilical cord compression is predictive of fetal condition in sheep.

OBJECTIVE: The purpose of this study is to assess the usefulness of the dynamic change in T/QRS ratio in fetal electrocardiograms in predicting the fetal condition when repetitive variable decelerations are seen in intrapartum cardiotocograms. STUDY DESIGN: We investigated the relationship, using linear regression and Wilcoxon's test, between T/QRS and blood gas values, catecholamine concentrations, and blood pressure during repetitive cord compression in five chronically instrumented lamb fetuses. RESULTS: T/QRS during cord compression correlated significantly (p less than 0.01) with fetal arterial pH (r = -0.7711), norepinephrine concentration (r = 0.7551), and duration of elevated blood pressure during compression (r = -0.8619). Fetal arterial pH and base excess were lower, the duration of elevated blood pressure during compression was shorter, and carbon dioxide partial pressure and catecholamine concentrations were higher in the stage with higher (greater than 0.50) T/QRS during compression (p less than 0.005). CONCLUSION: We can estimate the severity of fetal distress by measuring T/QRS near the bottom of the decelerations.

Animals↗
PubMed1992

Regression of coronary atherosclerosis by combined LDL-apheresis and lipid-lowering drug therapy in patients with familial hypercholesterolemia: a multicenter study. The LARS Investigators.

The purpose of the LDL-Apheresis Regression Study (LARS) group, which included 13 institutions in Japan, was to investigate the effects on coronary atherosclerosis of LDL-apheresis combined with cholesterol-lowering drugs. Changes in coronary artery stenosis were assessed angiographically in 37 patients with familial hypercholesterolemia (7 homozygotes and 25 heterozygotes) and hypercholesterolemia which had not been defined as familial hypercholesterolemia (5 patients) by visual judgement and computer analysis. Definite regression was observed in 14 cases, including 4 homozygotes and 10 heterozygotes and others. Regression occurred as often in patients with severe coronary artery disease (2 or more vessel disease) as in those having less severe disease. Our results encourage initiation of aggressive cholesterol-lowering therapy to produce regression of coronary atherosclerosis in FH patients at high risk for cardiovascular events.

Adult↗
PubMed1992

Multicentric development of pancreatic intraductal carcinoma through atypical papillary hyperplasia.

We report a case of multiple intraductal carcinomas of the pancreas associated with diffuse atypical papillary hyperplasia. A 67-year-old Japanese man with a complaint of epigastric pain was examined by endoscopic retrograde pancreatography, which demonstrated multiple dilated branches of the pancreatic duct in the body and tail of the pancreas. Histologic examination on the resected pancreas showed diffuse atypical papillary hyperplasia in multiple dilated ducts associated with multiple intraductal carcinomas. Histologic features are described and multicentric carcinogenesis through atypical papillary hyperplasia is discussed.

Aged↗
PubMed1992

Scoparic acid A, a beta-glucuronidase inhibitor from Scoparia dulcis.

The 70% EtOH extract of Scoparia dulcis showed inhibitory activity against beta-glucuronidase from bovine liver. Bioassay-directed fractionation of the active extract led to the isolation of three labdane-type diterpene acids, scoparic acid A [1] [6-benzoyl-12-hydroxy-labda-8(17), 13-dien-18-oic acid], scoparic acid B [2] [6-benzoyl-14,15-dinor-13-oxo-8(17)-labden-18-oic acid], and scoparic acid C [3] [6-benzoyl-15-nor-14-oxo-8(17)-labden-18-oic acid], the structures of which were established by spectral means, including X-ray analysis. Scoparic acid A was found to be a potent beta-glucuronidase inhibitor.

Acetylation↗
PubMed1992

Papillary adenoma of the pancreas with excessive mucin secretion.

A 68-year-old woman with papillary adenoma of the pancreas with excessive mucin secretion is reported. The patient was initially diagnosed as having chronic pancreatitis because of a history of repeated attacks of pancreatitis and localized dilatation of the main pancreatic duct. Four years later, endoscopic retrograde pancreatography showed markedly diffuse dilatation of the entire main pancreatic duct with amorphous filling defects of mucin. Excretion of mucin was observed through the enlarged orifice of Vater's ampulla. The patient was treated with distal pancreatectomy, and papillary adenoma with abundant mucin in the cytoplasm was histologically demonstrated. We describe unique clinical features of "mucin-producing pancreatic tumor" and discuss an important role of endoscopic retrograde pancreatography in the diagnosis.

Ampulla of Vater↗
PubMed1992

Preserved thyroidal secretion of thyroxine in acromegalic patients with suppressed hypophyseal secretion of thyrotrophin.

OBJECTIVE: We have assessed the mechanisms which maintain euthyroidism in acromegalic patients despite the suppression of thyrotrophin (TSH) secretion. MATERIALS: Fourteen untreated patients with acromegaly were analysed. Ten patients were also studied after pituitary surgery. METHODS: Thyroid hormones, growth hormone (GH), insulin-like growth factor-I (IGF-I) and thyroidal uptake of radioactive iodine, thyrotrophin releasing hormone (TRH) test and basal metabolic rate (BMR) were measured before and after pituitary surgery. RESULTS: Nine patients had palpable goitres. The TSH response to TRH stimulation was suppressed in eight patients, who maintained normal serum levels of total T3, T4 and free T4. The patients with normal TSH response had lower levels of free and total T4 than controls. The response of TSH to TRH correlated inversely with the serum level of total and free T4, and also with the plasma level of IGF-I (r = -0.74, P less than 0.05, n = 9). After pituitary surgery, the serum levels of total and free T4 were elevated for at least up to 6 months, with a decrease in the T3/T4 ratio and the BMR. CONCLUSION: GH may have a direct stimulatory action on the thyroid secretion of T4 possibly via increased IGF-I, despite suppressed TSH secretion. The post-operative elevation of serum T4 suggests the persistent secretion of T4 from the thyroid gland, in spite of instantaneous normalization of the accelerated conversion of T4 to T3, even after reduction of excess GH secretion.

Acromegaly↗
PubMed1992

Risk factors in the pregnancy of patients with systemic lupus erythematosus: association of hypocomplementaemia with poor prognosis.

Fetal wastage is still high in the pregnancies of patients with systemic lupus erythematosus (SLE). We examined retrospectively the cases of 38 patients with inactive SLE in whom pregnancy was either desired or had already been obtained. The prevalence of antiphospholipid antibodies in the group with fetal loss was high. The antibodies were, however, also detected in five of 14 patients who had had a live birth. It was noted that low levels of serum complement activity (CH50 less than 25 U/ml) occurred in five of six patients with fetal loss, but in only two of 22 with a live birth. Serial studies also confirmed a close association between decreased serum complement activity and poor fetal prognosis in lupus pregnancy. Treatment with increased doses of prednisolone may help to achieve successful live births. Thus hypocomplementaemia may be associated with a worse prognosis for the fetus in the pregnancies of some patients with SLE in remission.

Adult↗
PubMed1992

A probable case of superfecundation.

Discordant twins are of obstetrical concern because of high morbidity and mortality of either the smaller or the larger twin, or both. The discordance becomes apparent usually in the second trimester. We report a case of discordant twins diagnosed in the 10th week of gestation, which was concluded to be a case of superfecundation. The discordancy was persistent up to the 35th week of gestation, when 2 baby boys were born by cesarean section because of preeclampsia. The postnatal courses of the babies were uneventful.

Adult↗
PubMed1992

Small hyperechoic renal tumors displaying no fat content on CT.

We report two cases of small renal adenocarcinoma and one case of small angiomyolipoma, which were identified as hyperechoic tumors by ultrasonography. None of the three tumors displayed fat content on plain CT. Since CT cannot reliably identify the intratumoral structure of small hyperechoic renal tumors, we recommend intraoperative pathological examination when CT findings do not correspond with the results of ultrasonography.

Adult↗
PubMed1992

Synthesis of N-substituted C-normorphinans and their pharmacological properties.

Several N-substituted C-normorphinans (VIII and IX) were synthesized and tested for their analgetic and narcotic antagonist activities and physical dependence capacity. Treatment of N-formyl- octahydro-2-pyrindine (IIIc) with polyphosphoric acid readily gave N-formyl-C-normorphinan (IV). The N-nor bases (V and VII) obtained from IV were converted to VIII and IX. The N-methyl derivative (I), which was previously reported to be inactive by Haffner's method, exhibited potent analgetic activity by the hot plate method and the AcOH-induced writhing test. Compounds VIII and IX showed pharmacological properties similar to those of N-substituted morphinans and exhibited agonist (analgetic) and/or narcotic antagonist activities. The C-nor analogue (IXa) of cyclorphan (IIc) exhibited potent analgetic and antagonist activities with no physical dependence capacity in the single-dose suppression tests both in rats and monkeys.

Analgesics↗
PubMed1992

Synthesis of the optically active trans-isomers of diltiazem and their cardiovascular effects and Ca-antagonistic activity.

Optically active trans-isomers of diltiazem were synthesized and their cardiovascular effects were evaluated in anesthetized dogs and in isolated guinea pig hearts. Both (+)-2 (2R,3S) and (-)-2 (2S,3R) were much less active than diltiazem (1, 2S,3S) with short duration of action. No substantial enantiomeric difference in activity was seen between them. Their Ca-antagonistic activities on Ca(2+)-induced contractions in K(+)-depolarized canine basilar arteries were also examined. Absolute stereochemistry of (+)-2 was determined to be 2R,3S by X-ray crystallographic analysis.

Animals↗