Biomedical subjects

T Shono

Publications and source records attributed to T Shono.

At least 73 records · Page 4Linked to original sources

PubMed1998

Effect of retinoic acid on morphological changes of human pancreatic cancer cells on collagen gels: a possible association with the metastatic potentials.

Pancreatic carcinoma is an invasive and metastasizing type of malignancy. We established six pancreatic cancer cell lines from human pancreatic carcinomas, three highly metastatic lines (KP-1NL, KP-4, and SUIT-2) and three minimally metastatic lines (KP-2, KP-3, and BxPC-3). The three highly metastatic cell lines grew in a fibroblastoid pattern on collagen gels, whereas the three minimally metastatic cell lines grew in an epithelioid pattern under similar conditions. Western blot and Northern blot analyses indicated much higher levels of E-cadherin in the three minimally metastatic cell lines relative to the three highly metastatic cell lines. When the effect of all-trans-retinoic acid on the growth patterns of the three highly metastatic lines was examined, we observed a dramatic change from fibroblastoid to epithelioid growth in SUIT-2 cells. Although all six cell lines had comparable levels of retinoic acid receptor-gamma, retinoic acid receptor-beta was expressed only in SUIT-2 cells. Treating SUIT-2 cells with retinoic acid also induced the upregulation of E-cadherin expression. When SUIT-2 cells were treated with retinoic acid receptor-specific agonists, 13-cis-retinoic acid and Am555S, a morphological change from fibroblastoid to epithelioid growth was induced. Retinoic acid receptor-specific antagonists, LE135 and LE540, inhibited retinoic acid-induced change of the growth patterns. The effect of retinoic acid and its derivatives on the growth pattern was discussed in a possible association with their antimetastatic activities of pancreatic cancer.

Cadherins↗

PubMed1997

A novel member of lebocin gene family from the silkworm, Bombyx mori.

We screened genomic clones encoding lebocin, an antibacterial peptide from the silkworm, Bombyx mori. Two positive clones were obtained and their nucleotide sequences indicated that they contain no introns. The deduced amino acid sequences revealed that one clone (Leb 3) encoded lebocin 3 and another (Leb 4) is a new member of the lebocin gene family. Gene expression of both Leb 3 and Leb 4 was shown to be induced by lipopolysaccharide and to occur tissue-specifically in the fat body and hemocytes. Our results suggest that lebocin as well as cecropin forms a multiple gene family in B. mori.

Amino Acid Sequence↗

PubMed1997

Prenatal phthalate causes cryptorchidism postnatally by inducing transabdominal ascent of the testis in fetal rats.

Phathalate esters, which are commonly used as plasticizers for polyvinyl chloride, are also well known to disturb Sertoli cells. This study aims to show the effect of prenatally administered phthalate on testicular descent in pre- and postnatal rats. Pregnant rats were exposed to mono-n-butyl phthalate (MBP) by gavage from the 15th to the 18th gestational days. Rats administered with solvent only were used as controls. In 20-day-old fetuses (n = 15), the degree of transabdominal testicular ascent in relation to the bladder neck was thus found to be significantly higher in MBP-treated rats than that of the controls (n = 19). In addition, in MBP-treated male offspring (n = 26), 22 rats showed either bilateral or unilateral cryptorchidism at the age of 30 to 40 days old, and the occurrence of cryptorchidism was 84.6%. By contrast, the occurrence of cryptorchidism was 0% in the control rats (n = 15, P < .001). It is therefore suggested that prenatal exposure to MBP may disturb the Sertoli cells and elevate the fetal testes relative to the bladder neck while also inducing cryptorchidism postnatally. Sertoli cells may thus play an important role in the transabdominal descent of the testis by secreting Müllerian-inhibiting substance (MIS), which is known to act as a putative mediator of the transabdominal phase.

Abdomen↗

PubMed1997

Motility studies of the esophagus in a case of esophageal atresia before primary anastomosis and in experimental models.

Esophageal motility was assessed in a case of long-gap esophageal atresia (EA) without tracheoesophageal fistula before primary anastomosis, in addition esophageal manometrical studies were also experimentally performed in mongrel dogs to investigate the pathogenesis of the motility disorders in successfully repaired EA. Coordinated peristaltic contractions were observed between the proximal and distal esophageal pouch when swallowing before primary anastomosis in EA. In addition, these contractions induced a reflex relaxation of the lower esophageal sphincter (LES) as seen in the normal esophagus at the age of 8 months. At the age of 28 days, however, the LES showed an unstable pressure profile and the absence of a reflex relaxation in response to the contractions of the proximal esophageal pouch. On the other hand, experimental studies were carried out on six mongrel dogs weighing 12-15 kg. In group 1 (n = 3), the esophagus was divided at the level of the tracheal carina and both the proximal and distal pouches were closed separately. In group II (n = 3), the esophageal branches of the vagal nerves were divided between the level of the aortic arch and the esophageal diaphragmatic hiatus. Postoperatively, coordinated peristaltic contractions were shown between the proximal and distal esophageal pouches in group I, although the vagotomized esophagus showed abnormal simultaneous contractions in group II. These results suggested that even if the esophageal continuity is disrupted, the coordinated peristaltic contractions are propagated between the proximal and distal esophagus before primary anastomosis in EA, and thus postoperative esophageal motility disorders may result from the surgical damage to the vagus during operative procedures.

Anastomosis, Surgical↗

PubMed1997

Acetylcholinesterase (ACE) staining shows the abnormal innervation of a pulled-through rectum in a case of repaired anorectal malformation.

Abnormal innervation of the anorectum was noted in relation to anal incontinence in a case of repaired high-type anorectal malformation (ARM). A ten-year-old boy presented with anal incontinence after reconstructive surgery of ARM with a recto-urethral fistula. An anorectal manometrical examination revealed both an adequate tonus of the anal sphincter muscles and the absence of rectoanal reflex relaxation. And a barium enema showed a narrow region in the rectosigmoid colon, which was similar to that of Hirschsprung's disease (HD). Furthermore, an acetylcholinesterase (ACE) histochemical study of the rectal suction biopsies revealed an increased number of ACE-positive nerve fibers in the lamina propria mucosae and muscularis mucosae of the pulled-through colon. At the same time, however, some ganglia cells were also observed in the submucosa of the affected rectosigmoid colon and these cells could not be found in HD. Although the mechanism by which the abnormally innervated parasympathetic nerve fibers arose in the pulled-through colon remains unclear, this neuronal abnormality is considered to be the cause of anal incontinence in this case.

Acetylcholinesterase↗

PubMed1997

Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis.

Tumor necrosis factor alpha (TNF-alpha) is a macrophage/monocyte-derived polypeptide which modulates the expression of various genes in vascular endothelial cells and induces angiogenesis. However, the underlying mechanism by which TNF-alpha mediates angiogenesis is not completely understood. In this study, we assessed whether TNF-alpha-induced angiogenesis is mediated through TNF-alpha itself or indirectly through other TNF-alpha-induced angiogenesis-promoting factors. Cellular mRNA levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors were increased after the treatment of human microvascular endothelial cells with TNF-alpha (100 U/ml). TNF-alpha-dependent tubular morphogenesis in vascular endothelial cells was inhibited by the administration of anti-IL-8, anti-VEGF, and anti-bFGF antibodies, and coadministration of all three antibodies almost completely abrogated tubular formation. Moreover, treatment with Sp1, NF-kappaB, and c-Jun antisense oligonucleotides inhibited TNF-alpha-dependent tubular morphogenesis by microvascular endothelial cells. Administration of a NF-kappaB antisense oligonucleotide almost completely inhibited TNF-alpha-dependent IL-8 production and partially abrogated TNF-alpha-dependent VEGF production, and an Sp1 antisense sequence partially inhibited TNF-alpha-dependent production of VEGF. A c-Jun antisense oligonucleotide significantly inhibited TNF-alpha-dependent bFGF production but did not affect the production of IL-8 and VEGF. Administration of an anti-IL-8 or anti-VEGF antibody also blocked TNF-alpha-induced neovascularization in the rabbit cornea in vivo. Thus, angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms.

Animals↗

PubMed1996

Elicitors triggering the simultaneous gene expression of antibacterial proteins of the silkworm, Bombyx mori.

Various elicitors were examined by Northern blot analysis to investigate the simultaneous induction of gene expression of antibacterial proteins such as cecropin B, attacin and lebocin from the silkworm, Bombyx mori. Lipopolysaccharide (LPS), lipid A, 2-keto-3-deoxyoctonate (KDO) and peptidoglycan (PG) triggered efficiently and simultaneously the gene expression of antibacterial proteins. Effects of inhibitors for signal transduction on the gene expression of Bombyx mori (Bm) cecropin B triggered by lipid A were observed using isolated adherent hemocytes consisting of granular cells and plasma cells. H-7, H-89 but not W-7 inhibited gene expression, suggesting that protein kinase C and A but not myosine light chain kinase may participate in signal transduction.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1996

Angiogenesis as a new target for cancer treatment.

Neovascularization is often required for rapid growth of solid tumors and also limits vascular metastasis of tumor cells. Neovascularization-targeting agents are a recent innovation that may be a novel means of anticancer therapy. These antiangiogenic drugs have been developed by targeting cell proliferation of vascular endothelial cells, basement-membrane-degrading enzymes, angiogenic factors/receptors, extracellular matrix, angiogenesis signaling, and cell-cell/cell-matrix interactions. In this report, we describe how tumor angiogenesis occurs and how antiangiogenic agents are developed.

Animals↗

PubMed1996

Extraabdominal fixation of the gubernaculum inhibits testicular descent in newborn rats.

Within 48 hours after birth, newborn rats were anesthetized, and the distal tip of the gubernaculum was exposed extraabdominally, then fixed to the fascia of the groin on the left or the right side under a dissecting microscope (6x). In the sham-operated rats, the distal tip of the gubernaculum was merely exposed. Nonoperated rats were used as controls. In 60- to 90-day-old operated rats (n = 42), all testes were located in the superficial inguinal position, and the incidence of cryptorchidism was 100% on the operated side. In the sham-operated rats (n = 28), 27 of 28 testes descended into the scrotum, and one was located in the perineum; the incidence of cryptorchidism was 3.6% on the operated side. All testes also descended into the scrotum, and the incidence of cryptorchidism was 0% in controls (n = 20). The incidence of cryptorchidism was significantly higher among operated rats than among sham-operated or control rats (P < .001). The testicular weight and the germinal epithelia of the cryptorchid testes were significantly lower than those of the scrotal testes in both sham-operated and control rats. Therefore it is suggested that the extraabdominal fixation of the distal tip of the gubernaculum in newborn rats induces cryptorchidism. The present model is considered to be a simple and useful one to investigate the process of testicular maldescent and inhibited growth of the testis in cryptorchidism.

Animals↗

PubMed1996

Scanning electron microscopy shows inhibited gubernacular development in relation to undescended testes in oestrogen-treated mice.

The morphological relationship between transabdominal testicular descent and the 'swelling reaction' of the gubernaculum was investigated in oestrogen-treated fetal mice by using scanning electron microscopy (scanning EM). In addition, flutamide was also administered to pregnant mice to determine whether androgens cause gubernacular growth and transabdominal testicular descent in offspring. In oestrogen-treated fetal mice, scanning EM showed that both the gubernacular 'swelling reaction' and transabdominal testicular descent were inhibited, in addition to inhibition of Müllerian duct regression. The gubernaculum showed a flat, thin bulb (widest diameter 0.25 +/- 0.04 mm) and an elongated cord (1.28 +/- 0.41 mm) after oestrogen treatment in utero, which was significantly different in appearance from that in normal control mice (width 0.44 mm +/- 0.06 mm, p < 0.001; length 0.27 +/- 0.19 mm, p < 0.0001). However, flutamide-treated mice showed much more normal gubernacular enlargement and transabdominal testicular descent. The width of the gubernacular bulb after flutamide exposure was 0.44 +/- 0.05 mm, which was comparable to that in control animals; the length of the intra-abdominal gubernaculum (0.44 +/- 0.15 mm) was slightly longer than in controls (p < 0.02). These results suggest that both the swelling reaction of the gubernaculum and transabdominal testicular migration are blocked by prenatal exposure to oestrogen. However, oestrogen exposure of the fetus does not block the swelling reaction of the gubernaculum by acting as an antiandrogen.

Androgen Antagonists↗

PubMed1996

Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress.

Oxygen radicals are induced under various pathologic conditions associated with neovascularization. Oxygen radicals modulate angiogenesis in cultured human microvascular endothelial cells by an unknown mechanism. Treatment of human microvascular endothelial cells for 15 min with 0.1 to 0.5 mM hydrogen peroxide (H2O2) or 100 U of tumor necrosis factor alpha per ml induced tubular morphogenesis in type I collagen gels. Gel shift assays with nuclear extracts demonstrated that H2O2 increases the binding activities of two transcription factors, NF-kappaB and AP-1, but not of Spl. Tumor necrosis factor alpha increased the binding activities of all three factors. A supershift assay with specific antibodies against JunB, JunD, and c-Jun (Jun family) showed that the antibody against c-Jun supershifted the AP-1 complex after H2O2 treatment. Coadministration of the antisense sequence of NF-kappaB inhibited H2O2-dependent tubular morphogenesis, and the antisense c-Jun oligonucleotide caused partial inhibition. The angiogenic factor responsible for H2O2-induced tubular morphogenesis was examined. Cellular mRNA levels of vascular endothelial growth factor and interleukin-8 (IL-8), but not those of transforming growth factor alpha, were increased after treatment with 0.5 mM H2O2. Coadministration of anti-IL-8 antibody inhibited tubular morphogenesis enhanced by H2O2, and IL-8 itself also enhanced the formation of tube-like structures. Treatment with antisense NF-kappaB oligonucleotide completely blocked H2O2-dependent IL-8 production by endothelial cells. The tubular morphogenesis of vascular endothelial cells after treatment with oxidative stimuli and its possible association with NF-kappaB and IL-8, is examined.

Base Sequence↗

PubMed1995

Intracellular signal transduction of PBAN action in lepidopteran insects: inhibition of sex pheromone production by compactin, an HMG CoA reductase inhibitor.

Pheromone biosynthesis activating neuropeptide (PBAN) regulates sex pheromone production in the pheromone glands of many species of female moths. In order to probe the biochemical steps as well as underlying mechanisms regulated by PBAN, we have tested the effect of chemicals on sex pheromone production by using an in vitro assay. Among the chemicals we tested here, compactin, a specific 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, clearly inhibited the pheromone biosynthesis in the silkworm, Bombyx mori, and the common cutworm, Spodoptera litura. Since the activation of HMG CoA reductase occurs by dephosphorylation mediated by a specific phosphatase and the biochemical step regulated by PBAN in bombykol biosynthesis is similar to the one catalyzed by HMG-CoA reductase in cholesterol biosynthesis, the present results support the idea that phosphoprotein phosphatase has a significant role to regulate bombykol production in the intracellular transduction of PBAN action in B. mori.

Amino Acid Sequence↗

PubMed1995

Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors.

To examine which growth factors correlate with neovascularization in human brain tumors, the mRNA levels of transforming growth factor alpha, transforming growth factor beta, basic fibroblast growth factor, and vascular endothelial growth factor (VEGF) genes were determined by a Northern blot analysis in surgically obtained human gliomas and meningiomas. The vascular development was determined by counting the number of microvessels which were immunostained with von Willebrand factor. We normalized the growth factor mRNA levels versus the glyceraldehyde phosphate dehydrogenase mRNA level. In the 17 gliomas and 16 meningiomas examined, the mRNA of transforming growth factors alpha and beta, basic fibroblast growth factor, and VEGF were expressed at various levels. Among those 4 growth factors, the mRNA levels of VEGF, but not those of transforming growth factors alpha and beta and basic fibroblast growth factor, correlated significantly with vascularity in both gliomas (correlation coefficient r = 0.499; P < 0.05) and meningiomas (correlation coefficient r = 0.779; P < 0.001). These findings thus suggest that VEGF may be a positive factor in tumor angiogenesis in both human gliomas and meningiomas.

Brain Neoplasms↗

PubMed1995

Physiological effects in vitro of calcitonin gene-related peptide on gubernacular contractility with or without denervation.

The gubernaculum in neonatal rats has been shown previously by direct observation to contract rhythmically in response to exogenous calcitonin gene-related peptide (CGRP), but the physiological properties of these contractions were unknown. In the first study the authors investigated gubernacular contractility in vitro using a strain gauge to see if there were characteristics of skeletal or smooth muscle. Both the frequency and the amplitude of contractions were significantly enhanced by CGRP, and isotonic tension of the gubernaculum and the duration of contractions were also increased after CGRP. The effect of CGRP on gubernacular contractions appeared several minutes after adding CGRP, and it was independent of the acetylcholine action, which induced only a single twitch response of the gubernaculum. In the second study the authors investigated the effect on gubernacular contractility of prior transection of the genitofemoral nerve (GFN), which contains CGRP. Vigorous contractions occurred in 85% of denervated gubernacular compared with 46% of controls (P < .01). These data provide the first quantitative evidence of rhythmic gubernacular contractions, and suggest that CGRP enhances gubernacular contractility by a direct effect independent of acetylcholine. Further, the contractile properties resemble those of differentiated cardiac muscle or primitive embryonic skeletal muscle. GFN transection enhances the gubernacular contractile response to exogenous CGRP, which is consistent with the GFN being the normal source of CGRP for the gubernaculum in vivo.

Animals↗

PubMed1995

The effect of the excision of future scrotal skin on testicular descent in neonatal rats: a new experimental model of cryptorchidism.

The ingunoscrotal skin of neonatal rats was widely excised on either the right or left side to examine the role of the scrotum in testicular descent. At the age of 10 days, gubernacular migration was observed to be significantly inhibited on the operated side in comparison with that on the nonoperated side. At the age of 60 to 90 days, 12 of 17 testes on the operated side were located in the superficial inguinal position, 2 were in the perineum, and another 3 had descended into the contralateral nonoperated scrotum. All the testes descended into the scrotum on the nonoperated side and in the normal control rats. Though the histological development was remarkably inhibited in the cryptorchid testis, the contralateral descended testis did show the same histological appearance as that of the control testes in 90-day-old rats. This new model of cryptorchidism is considered to provide a simple technique for investigating the mechanism of testicular descent and the impaired development of the testes in cryptorchidism.

Animals↗

PubMed1995

Chemotherapy for progressive pilocytic astrocytomas in the chiasmo-hypothalamic regions.

Over the past 25 years, we have treated 17 patients with chiasmo-hypothalamic astrocytomas. Before 1988, the initial treatments consisted of surgery and/or radiotherapy, while since 1989, 4 children (1 male, 3 females, aged 3-8 years) were treated primarily with chemotherapy. None of them was associated with neurofibromatosis. After a biopsy of the tumor, the intravenous administration of ranimustine (MCNU; 30-86 mg/m2) and/or nimustine (ACNU; 30.3-64.1 mg/m2) was given without radiation therapy. Chemotherapy was usually given as an out-patient, with a total of 5-13 courses. The total doses of MCNU and ACNU administered ranged from 150 to 570 mg and from 64.8 mg to 100 mg, respectively. After chemotherapy 2 patients showed clinical improvement and tumor regression on neuro-imaging, while one patient showed clinical improvement and tumor size stabilization on neuro-imaging. The remaining one child, however, showed a clinical worsening and tumor progression on neuro-imaging studies. He was thus treated with a second chemotherapy regimen with carboplatin and etoposide, which brought about tumor regression. The acute and subacute toxicity of chemotherapy was mild. All patients are now leading almost normal lives with a median of 43 months after diagnosis. Although a longer and more careful clinical observation is required, the authors conclude that chemotherapy with MCNU and/or ACNU may benefit patients with unresectable pilocytic astrocytoma requiring treatment. The advantages of this therapy include its mild side effects and the lack of any hospitalization in most patients. It may also delay the need for radiation therapy, which can have a deleterious effect on the young developing brain.

Antineoplastic Agents↗

PubMed1995

Dual pathways of tubular morphogenesis of vascular endothelial cells by human glioma cells: vascular endothelial growth factor/basic fibroblast growth factor and interleukin-8.

In this study, we examined whether human glioma cells are angiogenic in a model using human microvascular endothelial cells, and also which factor is responsible for the glioma-dependent angiogenesis. Tubular morphogenesis in type I collagen gel by human microvascular endothelial cells was stimulated in the presence of 10 and 100 ng/ml of vascular endothelial growth factor (VEGF), 10 ng/ml basic fibroblast growth factor (bFGF) and 10 ng/ml of interleukin-8 (IL-8). Tube formation of the microvascular endothelial cells was assayed in the glioma cell lines IN157 and IN301, co-cultured using the double chamber method. IN301 cells had much higher levels of VEGF, bFGF and transforming growth factor-beta mRNA than IN157 cells, whereas the two had similar levels of transforming growth factor-alpha mRNA. By contrast, IN157 cells had much higher levels of IL-8 mRNA than IN301 cells. IN301-dependent tubular morphogenesis was inhibited by anti-VEGF or anti-bFGF antibody, and the inhibition was almost complete when anti-VEGF and anti-bFGF antibodies were present. On the other hand, IN157-dependent tubular morphogenesis was inhibited by anti-IL-8 antibody, but not by anti-VEGF or anti-bFGF antibodies. These findings demonstrated dual paracrine controls of tumor angiogenesis by human glioma cells. One is mediated through VEGF and/or bFGF, and the other, through IL-8.

Astrocytoma↗

PubMed1995

Intracellular transduction in the regulation of pheromone biosynthesis of the silkworm, Bombyx mori: suggested involvement of calmodulin and phosphoprotein phosphatase.

We have tested the effects of chemicals on bombykol production in vitro in the silkworm, Bombyx mori, to probe the biochemical steps as well as underlying mechanisms regulated by PBAN. These results suggest the involvement of calmodulin and phosphoprotein phosphatase in the intracellular signal transduction of PBAN action.

Amino Acid Sequence↗