Search PubMed⌕ Search

Biomedical subjects

M Kanzaki

Publications and source records attributed to M Kanzaki.

At least 91 records · Page 5Linked to original sources
PubMed1995

A single intraportal administration of follistatin accelerates liver regeneration in partially hepatectomized rats.

BACKGROUND/AIMS: Activin A is an autocrine negative regulator of DNA synthesis in rat hepatocytes and is expressed in remnant liver after partial hepatectomy. To determine the role of activin A in liver regeneration, the effects of exogenous follistatin, which blocks the action of activin A, were examined. METHODS: Human recombinant follistatin was infused into the portal vein immediately after 70% hepatectomy. Changes in body weight, remnant liver weight, liver regeneration rate, and nuclear bromodeoxyuridine labeling were measured. RESULTS: In control rats, nuclear labeling was observed at 24 hours and peaked at 36 hours after the hepatectomy. In follistatin-treated rats, nuclear labeling was first observed after 18 hours and was significantly (P < 0.05) greater than that in control rats at 24 hours. In follistatin-treated rats, both remnant liver weight and liver regeneration rate were significantly greater at 120 hours. Serum concentrations of albumin and glucose remained reduced for up to 120 hours in control rats but recovered in follistatin-treated rats. CONCLUSIONS: A single administration of follistatin accelerates the initial round of DNA synthesis after partial hepatectomy. Activin A produced in remnant liver may exert tonic inhibitory effect on liver regeneration. Follistatin may be useful as a potential therapeutic agent to promote liver regeneration.

Activins↗
PubMed1995

Derangements in the activin-follistatin system in hepatoma cells.

BACKGROUND/AIMS: The growth of normal hepatocytes is regulated by the activin-follistatin system. The aim of this study was to investigate the activin-follistatin system in hepatoma cells. METHODS: The production and action of activin and follistatin in human hepatoma cell lines were examined. Activin A and follistatin were measured by bioassay and protein-binding assay, respectively. RESULTS: Activin A inhibited cell growth in HepG2 cells but not in either PLC/PRF/5 or HLE cells. However, the effect of activin A in HepG2 cells was attenuated at high cell density. In HepG2 cells, two classes of activin-binding sites were expressed, and affinity cross-linking showed that 125I-activin A bound specifically to three proteins with molecular weights of 48, 67, and 94 kilodaltons. In PLC/PRF/5 cells, a single class of binding site was observed, and the binding capacity was approximately 60% of the capacity in HepG2 cells. Virtually no 125I-activin A binding was detected in HLE cells. Bioactivity and messenger RNA for activin A were undetectable in three cell lines. In contrast, follistatin was released from three cell lines. CONCLUSIONS: Multiple alterations in the activin-follistatin system were found in three hepatoma cell lines. The accelerated growth observed in hepatoma cells may be caused, at least partly, by the attenuation of the action of activin A.

Activins↗
PubMed1995

Alteration of the hypothalamus-pituitary-testis axis in oligozoospermic men with normal gonadotropin levels.

BACKGROUND: Serum basal hormone levels such as lutenizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone, which is important to regulate testicular function, do not necessarily indicate the normal integrity of the hypothalamic-pituitary-testicular axis and the static measurement is not enough to detect the endocrine disorder. The dynamic measurement of gonadal hormone by GnRH test is considered to be more helpful to understanding the endocrine regulation of spermatogenesis. In this study, we performed GnRH test in oligozoospermic patients with normal levels of LH and FSH to examine the subtle alteration of hypothalamic-pituitary-testis axis. METHODS: GnRH test was performed in 41 patients with oligozoospermia and normal gonadal hormone levels. RESULTS: The responses of LH and/or FSH were excessive in most patients in spite of their normal gonadotropin levels. The patients with sperm concentration < 10 x 10(6)/ml had significantly higher peak levels of both LH and FSH than did those with sperm concentration > 10 x 10(6)/ml. In the patients with normal peak levels of both LH and FSH, sperm concentration was significantly higher than those with exceeded peak levels of FSH and/or LH after GnRH test. No significant differences were observed in estradiol, testosterone, free testosterone, or prolactin (PRL) levels between patients with normal responses and abnormal responses of LH and/or FSH. CONCLUSIONS: The feedback control of gonadotropin release from testis was worse in more severely oligozoospermic patients, although the precise mechanism of feed back still remains unknown.

Adult↗
PubMed1995

Modulation of adenosine triphosphate-sensitive potassium channel and voltage-dependent calcium channel by activin A in HIT-T15 cells.

The ATP-sensitive potassium channel (KATP channel) determines the membrane potential of pancreatic beta-cells and plays a critical role in the regulation of insulin secretion. The present study was conducted to investigate the effect of activin A, a member of the transforming growth factor-beta supergene family, on the KATP channel in HIT-T15 clonal hamster insulinoma cells. In an excised inside-out patch, ATP-sensitive currents with a single channel conductance of approximately 20 picosiemens were observed. In an outside-out patch, currents with identical unitary conductance were also observed. In either case, the currents were augmented by diazoxide and blocked by glibenclamide, verifying that they were KATP channel currents. When KATP channel currents were monitored in an outside-out patch, activin A added to the bath solution inhibited KATP channel currents. Upon removal of activin A, the KATP channel currents were restored, suggesting that the inhibition was not due simply to spontaneous disappearance of channel activity (run-down). The KATP channel activity was markedly reduced after the addition of activin A and was reversed by diazoxide. Besides the inhibition of KATP channel, activin A increased, in a perforated patch, the amplitude of the inward Ba2+ current in response to a depolarizing pulse from -40 to +10 mV. Under the current clamp condition, activin A induced gradual depolarization, followed by a burst of action potentials. Activin-mediated action potentials were accompanied by an elevation of the cytoplasmic free calcium concentration. These results indicate that activin A causes depolarization of the plasma membrane by inhibiting the activity of the KATP channel. In addition, activin A directly modulates the voltage-dependent calcium channel and augments calcium entry.

Action Potentials↗
PubMed1994

Stimulation of follistatin production by epidermal growth factor in cultured rat hepatocytes.

Production of follistatin in cultured rat hepatocytes was studied by measuring follistatin release with a protein-binding assay using [125I]activin A. Follistatin was detected in conditioned medium of cultured hepatocytes. Ligand blotting using [125I]activin revealed that follistatin released into the medium consisted of two different forms with molecular weight of approximately 40 K-Da. Epidermal growth factor (EGF) elicited dose-dependent increases in DNA synthesis and follistatin release. Dose-response relationship for EGF-induced follistatin release correlated well with that for EGF-induced DNA synthesis. In EGF-stimulated cells, a marked increase in DNA synthesis occurred after 48 hrs. Similarly, follistatin release was markedly augmented after 48 hrs. Amount of cell-bound follistatin was not changed by the treatment with EGF. These results indicate that cultured hepatocytes synthesize and release follistatin. The activin-follistatin system operates in cultured rat hepatocytes and may modulate DNA synthesis by altering the action of activin A.

Activins↗
PubMed1994

Granulosa cell luteinizing hormone receptor expression is modulated by ganglioside-specific ligands.

The ganglioside GM1 (Gal beta 1-->3GalNAc beta 1-->4[NeuAc alpha 2-->3] Gal beta 1-->4Glc beta 1-->1Cer) was synthesized during granulosa cell development in vitro, and the effect of the interaction between cell-surface GM1 and its ligands on the luteinizing hormone (LH) receptor expression was investigated. GM1 synthesis, demonstrated by metabolic labeling of glycosphingolipids with [3H]galactose and binding studies using the 125I-B-subunit of cholera toxin, a specific ligand for GM1, was increased in follicle-stimulating hormone (FSH)-treated granulosa cells. When granulosa cells were cultured for 72 h in a medium containing the B-subunit of cholera toxin, FSH-induced LH-receptor contents determined by measuring the binding of 125I-deglycosylated human chorionic gonadotropin to intact cells, was augmented. The stimulatory effect of the B-subunit was dependent on the FSH concentration and culture duration. The augmentation was observed after culture for 48 h, and marked increases were evident after 72 h, which coincided with an increase of the 125I-B-subunit binding capacity. Scatchard analysis of the LH-receptor binding indicated that treatment with the B-subunit increased the number of LH-binding sites (6580 sites/cell after treatment with 20 ng/ml FSH; 11,290 sites/cell after FSH plus 100 ng/ml B-subunit), but did not alter the binding affinity. A specific antibody against GM1 mimicked the stimulatory effect of the B-subunit. The augmentation was not accompanied by granulosa cell proliferation. These findings suggest that binding of exogenous or possible endogenous ligands to cell-surface GM1 produces signals and modulates the cellular behavior during granulosa cell development.

Animals↗
PubMed1994

Basic fibroblast growth factor induces luteinizing hormone receptor expression in the presence of insulin-like growth factor-I in ovarian granulosa cells.

Effect of basic fibroblast growth factor (bFGF) on the expression of receptors for luteinizing hormone (LH), a marker of differentiation, was studied using estrogen-primed rat ovarian granulosa cells in primary culture. bFGF had no effect by itself but dose-dependently induced expression of functional LH receptors in the presence of insulin-like growth factor-I (IGF-I). The effect of a combination of bFGF and IGF-I was delayed in onset and the magnitude of the response was smaller when compared to the action of follicle-stimulating hormone (FSH). Scatchard analysis revealed that dissociation constant (Kd) and number of LH receptors induced by bFGF and IGF-I were 0.47 nM and 6.48 fmol/10(6) cells, respectively. Unlike FSH, bFGF plus IGF-I did not cause an immediate increase in cAMP release, however, considerable amount of cAMP release was observed in cells incubated for 72 h with bFGF plus IGF-I. Indomethacin, an inhibitor of cyclooxygenase, attenuated both LH receptor expression and cAMP release induced by bFGF plus IGF-I but had little effect on the action of FSH. Finally, a combination of bFGF and IGF-I increased production of prostaglandin E2 in granulosa cells. These results indicate that bFGF is capable of inducing LH receptor in the presence of IGF-I by a mechanism involving production of prostaglandin E2.

Animals↗
PubMed1994

Co-ordinate actions of FSH and insulin-like growth factor-I on LH receptor expression in rat granulosa cells.

The actions of FSH and Insulin-like growth factor-I (IGF-I) were studied in cultured rat ovarian granulosa cells. Cells became differentiated and expressed LH receptors when they were incubated for 72 h with 200 micrograms FSH/l (high FSH) but not 20 micrograms FSH/l (low FSH). Treatment with high but not low FSH increased the release of both immunoreactive and bioactive IGF-I into the medium. A combination of low FSH and IGF-I reproduced the effect of high FSH on LH receptor expression. We then examined the critical time when low FSH and IGF-I exerted their effects. In the presence of continuous low FSH, IGF-I was capable of inducing LH receptor expression even when added 24 h after the addition of low FSH. However, when IGF-I was added at 36 h, LH receptor expression measured at 72 h was greatly reduced. In contrast to the action of IGF-I, continuous exposure to low FSH was required for LH receptor expression, and IGF-I had no effect when FSH was not included for the entire 72 h of culture. DNA synthesis as assessed by both [3H]thymidine incorporation and nuclear bromodeoxyuridine labelling was moderate at the beginning of culture and markedly reduced at 24 h both in the presence and absence of either high FSH or low FSH plus IGF-I. In the presence of either high FSH or a combination of low FSH plus IGF-I, DNA synthesis remained decreased for up to 72 h whereas it began to increase in the absence of either high FSH or a combination of low FSH plus IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Human growth hormone augmentation of epidermal growth factor binding sites on rat granulosa cells.

The effect of human GH (hGH) on the regulation of epidermal growth factor (EGF) receptor was investigated during differentiation of FSH-treated rat granulosa cells, which has been reported to be mediated by a cAMP-dependent mechanism. By measuring the binding of [125I]iodo-EGF to the intact cells, FSH was shown to cause increases in the number of EGF binding sites after culture for 72 h. When granulosa cells were cultured with hGH, the number of FSH-induced EGF binding sites was augmented, with a half-maximal effect at about 10 micrograms hGH/l and a maximal stimulatory concentration of 100 micrograms/l. The stimulatory effect of hGH was absolutely dependent on insulin which by itself showed stimulatory effects on EGF binding sites. Scatchard analysis of EGF binding sites indicated that treatment with hGH increased the number of EGF binding sites (17,200 sites/cell after treatment with FSH; 31,700 sites/cell after FSH plus hGH), but did not alter the binding affinity. The augmentation was observed after culturing for 48 h and increased progressively with time, reaching 280% of the level after FSH treatment by 120 h. Although progesterone synthesis was increased by hGH, the markers of cell differentiation such as cAMP synthesis and LH binding sites were suppressed, indicating hGH inhibition of the cAMP-mediated signal. The action of hGH on the EGF binding sites was not accompanied by cell proliferation. These findings indicate that hGH has a novel action on the regulation of rat granulosa cell EGF binding sites and that the granulosa cell may possess both cAMP-dependent and -independent mechanisms for expression of EGF binding sites.

Animals↗
PubMed1993

[A case of malignant mesothelioma of the tunica vaginalis testis].

A case of malignant mesothelioma of tunica vaginalis testis experienced in an 83-year-old male who presented with a complaint of left intrascrotal pain is reported. The tentative diagnosis was acute epididymitis. Left epididymectomy was performed following the unsuccessful treatment with antibiotics. The histology of the surgical specimen revealed malignant mesothelioma. Radical excision of the left spermatic cord and scrotal content indicated locally advanced disease with positive surgical margin. Metastatic workup, including abdominal and chest computerized tomography scan, magnetic resonance imaging and bone scan demonstrated presence of metastasis to the paraaortic lymph nodes and the lumber spine. The patient is being followed conservatively in consideration of his age and advanced stage of the disease.

Adult↗
PubMed1993

[Growth factors in the pituitary gland].

There are increasing numbers of evidence that many factors, such as growth factors and cytokines, exist in the pituitary gland, and modulate the release of pituitary hormone both in vivo and in vitro. They indicate the importance of autocrine and paracrine control system within the pituitary gland. For instance, activin, a compound whose existence and nature (in contrast to the related protein inhibin) was not contemplated before its discovery in 1986, has been shown to be synthesized in gonadotrophs and to produce diverse effects on the anterior pituitary. We would like to introduce some recent studies on growth factors in the pituitary gland.

Activins↗
PubMed1991

Further immunohistochemical study of Crooke's hyalin.

For analysis of the cytokeratin (CK) of Crooke's cells, 28 post-mortem pituitary glands with unequivocal Crooke's hyaline change were investigated immunohistochemically using monoclonal antibodies for CK subfamilies. Crooke's hyalin was positive for CK 8 [molecular weight 52.5 kilodalton (KD)] and 18 (45 KD) but negative for skin-, cornea- and esophageal-typed CKs.

Antibodies, Monoclonal↗
PubMed1991

Prevalence of Listeria monocytogenes in intestinal contents of healthy animals in Japan.

A total of 1,705 fecal specimens or ileo-cecal contents of cattle, pigs, dogs, cats, chicken and rats were submitted for the isolation of Listeria monocytogenes by the use of the combination of Oxford-LPM agar plates after the cold enrichment in PBS at 4 degrees C for 4-6 weeks. Prevalence of L. monocytogenes was found to be 1.9% in cattle, 0.6% in pigs, 0.9% in dogs and 6.5% in rats. However, none of L. monocytogenes was isolated from chicken or cats. Among 26 isolates of L. monocytogenes, 13 strains (50%) were classified into types 1/2a (3 strains), 1/2b (5 strains) and 4b (5 strains) and were often associated with human listeriosis. The majority of the Listeria spp. other than L. monocytogenes isolated from these animals was found to be L. innocua.

Animals↗
PubMed1991

[A case of acinar-islet cell tumor of the pancreas body].

Combined carcinoma of the pancreas is very rare. The case of pancreatic tumor featuring both acinar cell and islet cell tumors presented, may be only the fifth case of acinar-islet cell tumor in the world. A 34-year-old-woman visited our hospital complaining of weight loss (8 kg/6 months). A clearly demarcated pancreatic tumor was visualized by ultrasonography, body CT and MRI. Class 3 cells were extracted via ultrasonography guided fine-needle biopsy. Tumor was enucleated on October 5, 1988. Histologic appearance of the tumor by light microscopy was consistent with that of both acinar cell and islet cell tumors. Electron microscopy revealed two distinct populations of zymogen and neuroendocrine granules. The patient is doing well 1 year and 7 months postoperatively with no evidence of liver metastasis or recurrence. This case is significant in terms of the close histogenic relationship between pancreatic exocrine and endocrine components.

Adenoma, Islet Cell↗
PubMed1991

[A case of chest wall rhabdomyosarcoma].

A 56-year-old man was admitted to our hospital with right chest pain. Chest X-ray, CT scan and MRI revealed a chest wall tumor and enlarged mediastinal lymph nodes. Percutaneous lung biopsy was performed, and the pathological diagnosis of pleomorphic rhabdomyosarcoma was obtained. The only significant abnormal laboratory finding was elevation of serum NSE (24.5 ng/ml). Although chemotherapy (VAC-ADM) and radiation therapy were performed, the patient died about 7 months after admission. To our knowledge, only 17 cases of chest wall rhabdomyosarcoma have been reported in Japan.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Choroid plexus hemangioma with port-wine nevus of the face: relationship to Sturge-Weber syndrome--case report.

The authors describe a case of choroid plexus hemangioma in a 49-year-old male. Computed tomographic scan showed an isodense mass at the trigone of the right lateral ventricle with homogeneous enhancement. He also displayed a port-wine nevus on the ipsilateral side of the face. At operation, the tumor was found not to adhere to the lateral ventricular wall but to be connected to the choroid plexus, and was colored similarly to the facial nevus. Histological examination showed a capillary hemangioma with many crowded capillaries. This case was not included in the category of Sturge-Weber syndrome but is thought to be closely related, considering the syndrome from the viewpoint of generalized neurocutaneous hemangiomatosis.

Cerebral Ventricle Neoplasms↗
PubMed1988

Intramitochondrial inclusions caused by depletion of creatine in rat skeletal muscles.

Effect of creatine depletion by beta-guanidinopropionic acid (beta-GPA) feeding on mitochondrial morphology was studied in rats. Following beta-GPA feeding for 9 weeks, intramitochondrial inclusions running parallel to the long axis of mitochondrion were observed in skeletal muscles. A bundle of inclusions consisted of four parallel arrays containing electron-dense materials. Two outer arrays were continuous with cristal membranes and two inner arrays were chains of fine particles. Mitochondria with such inclusions were elongated probably in only a certain direction even though it was suggested that the layers of cristae were straightened two-dimensionally. Longer mitochondria ran parallel to the muscle fibers. It was also suggested that chronic stimulation of mitochondrial biogenesis by depletion of high energy phosphates may induce such inclusions within mitochondria.

Adenosine Triphosphate↗