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K Kurisu

Publications and source records attributed to K Kurisu.

At least 181 records · Page 10Linked to original sources

In vivo effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors.

Cabergoline (CG) is a dopamine agonist that inhibits the secretion of prolactin (PRL) and growth hormone. In the present study, we evaluated the in vivo effect of CG on PRL secretion and the pituitary tumor induced by estrogen. Estrogen was administered by subcutaneous injection to 4-week-old Fischer 344 rats weekly for 10 weeks to induce tumors. On the last day of estrogen administration, doses of either CG or bromocriptine (BC), 0.6 mg/kg, were administered as a single oral route or chronically, given every third day. Sera and pituitary tumors were sampled on each treatment schedule. Serum levels of PRL were measured and the pituitary glands were weighed. Immunohistological evaluation was performed by optical and electron microscopy. A single dose of CG significantly inhibited the serum levels of PRL for 6 days. Following a single dose of BC, the PRL level was significantly inhibited only at 6 hours' postadministration. The continued oral administration of CG significantly reduced both the serum PRL level and the weight of the pituitary during 15 to 60 days of treatment as compared with BC. Morphologic studies revealed that CG reduced the size of the cells and of the granules, and increased the number of granules per unit area of the cytoplasm. These findings suggest that CG inhibits the maturation of PRL secretory granules and the secretion of PRL more than its synthesis. Thus, CG induced a prolonged lowering of PRL and had a good antitumor effect on rat pituitary tumors induced by estrogen.

Animals↗

Effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors: in vitro culture studies.

Cabergoline (CG) is a dopamine agonist that inhibits secretion of prolactin (PRL) and growth hormone. The purpose of this study was to investigate the PRL-lowering effect and antitumor effect of CG on estradiol-induced rat pituitary tumors in vitro and to elucidate these mechanisms. We compared the effects of CG with those of bromocriptine (BC) in terms of the inhibition of hormone secretion as well as antitumor effects on rat pituitary tumors. Primary cultures of dissociated pituitary tumor cells were used in these studies. A significant inhibition of prolactin (PRL) secretion was observed for both drugs within 12 h after treatment, and the inhibitory effects of CG and BC were antagonized by sulpiride or haloperidol. Inhibitory effect on PRL secretion after 12-h BC or CG pretreatment was more pronounced with CG than BC treatment at all time points. PRL secretion in group pretreated with CG was significantly suppressed at 72 h when compared to that of vehicle. Inhibition of de novo PRL synthesis was better demonstrated in the CG group. These findings suggest that CG has a higher affinity for the D2 receptor of pituitary cells as compared to BC and may preferentially inhibit PRL secretion rather than PRL production. An antitumor effect of CG has been confirmed at a lower dosage than that of BC.

Animals↗

Anterior pituitary function in patients with nonfunctioning pituitary adenoma: results of longitudinal follow-up.

Studies of anterior pituitary function in patients treated for nonfunctioning pituitary adenomas have been limited by their short duration. The purpose of the present study was to examine pituitary function longitudinally among three types of patients: those with complete tumor removal (group A); those with subtotal or partial adenomectomy (group B); and those in group B who underwent additional radiation therapy (group C). The subjects were 33 patients whose anterior pituitary function was evaluated by provocative tests such as insulin induced hypoglycemia, thyrotropin releasing hormone administration test and luteinizing hormone releasing hormone administration test. They underwent preoperative evaluation and postoperative reevaluations at 2 weeks, 3 months, 6 months and annually thereafter, for over 10 years. Anterior pituitary function was restored within a year after surgery, if at all. No additional function was restored after one year from treatment. In group A, no one developed impairment of anterior pituitary function after one year from surgery. In group B, however, new impairment was noted at intervals, due to tumor regrowth. In Group C, deficiencies developed after one year, irrespective of tumor regrowth. In conclusion, lifelong endocrinological follow-up is recommended for patients receiving postoperative irradiation, and for patients with potential for tumor regrowth. On the other hand, patients with total adenomectomy may be exempted from periodic endocrinological follow-up if they do not need postoperative hormonal replacement therapy.

Adenoma↗

Influence of daily subcutaneous administration of reserpine for 4 weeks or 9 weeks before mating on testis, sperm and male fertility in rats.

To determine the optimum period of drug treatment and assessment parameters to evaluate male fertility in rats, different methods of examination and periods of treatment before mating were investigated in Sprague-Dawley (Crj:CD) male rats treated with a testicular oxicity-inducing agent, reserpine. The rats were given reserpine subcutaneously at daily doses of 0.05, 0.1 and 0.2 mg/kg for 4 and 9 weeks (4-week test and 9-week test). Reproductive performance was tested and after mating, the testes, epididymides, prostate and pituitary weights were measured. Sperm analysis and histopathological examinations of the genital organs were also performed in the 4-week test case. After 4 weeks, prostate weight was decreased and the implantation rate showed a tendency for decrease. Histopathological examination of the testes revealed changes such as retention of step 19 spermatids in the seminiferous tubules of stages IX to XII, although sperm analysis showed no abnormal findings. In the 9-week test, testes and prostate weights were decreased along with the implantation rate was decreased. In conclusion, of the approaches used to evaluate the effects of reserpine on male fertility, histopathological examination and measurement of genital organ weights proved more sensitive than reproductive performance testing and sperm analysis. Regarding the optimum treatment period, 4 weeks was found to be sufficient for detection of histopathological and genital organ weight changes.

Animals↗

[A case report of cranial bone defect with a porencephalic cyst in an adult].

A case of cranial bone defect with porencephalic cyst in an adult was reported. A 47 year-old male was admitted with epilepsy. He had a round lytic bone defect lesion in the left frontal skull. The porencephalic cyst was under the bone defect. The mechanism of bone defect is thought to be as follows. He had received some head trauma in childhood and the frontal skull bone had fractured. The contusioned brain changed to a porencephalic cyst. The linear bone fracture may have enlarged according to the mechanism of a growing skull fracture. Persistent pulsative pressure from the porencephalic cyst toward the fractured bone edge might be able to make the bone defect oval.

Brain Diseases↗

Changes of motor evoked potentials in global and focal ischemic models of cats.

In order to evaluate the significance of motor evoked potentials (MEPs) in central nervous system monitoring, the authors conducted two sets of experiments using feline ischemic models. Twenty-three adult mongrel cats were divided into two groups: global (n = 9) and focal ischemic (n = 14) groups. In the case of global ischemia, which was induced by hypovolemic hypotension due to blood letting, deterioration of the D wave began when the mean arterial blood pressure (MABP) approached 45 mmHg, and regional cerebral blood flow (rCBF) dropped to 40% of control. Complete disappearance of the D wave was observed below 30 mmHg in MABP and 20% of control in rCBF. In the case of focal ischemia, which was induced by transorbital occlusion of the middle cerebral artery, the percentages of rCBF at which the D wave disappeared ranged from 9 to 20%. Changes in the amplitude of the D wave--an increase and following decrease--preceded the prolongation of its latency. In contrast with the D wave I waves were too easily affected by ischemia. Moreover, rCBF at the point of disappearance of the I wave varied greatly. In conclusion, the D wave is stable in mild ischemia and is a reliable indicator of critically profound ischemia (%rCBF < 40%). Monitoring the D wave of MEPs seems to be a useful method for avoiding the deterioration of motor function by ischemic insult.

Animals↗

[Antitumor effect of intra-arterial tumor necrosis factor-alpha in rats with transplanted intracerebral glioma and its evaluation by MRI].

Recombinant human TNF-alpha was administrated intra-arterially to rats with transplanted intracerebral glioma. 1 x 10(6) of T9 rat glioma cells were transplanted into Fisher 344 rat brain stereotaxically and 1000 units of TNF-alpha was administrated at a rate of 100 microl/min. via an internal carotid artery 1 or 3 weeks after the transplantation. The effects of TNF-alpha were evaluated by MRI and histopathological examinations. Neurological symptoms, i.e. hemiparesis, appeared after 9.0 +/- 0.63 days and all rats died of tumor overloading 14.5 +/- 0.84 days after the transplantation. Single injection of TNF-alpha on 7th day after the transplantation induced regression of the tumor size in one of six rats. The tumors were detected 3 days after transplantation by MRI and they were revealed as low/iso intensity mass in T1WI, iso/high intensity in T2WI, and were enhanced by Gd-DTPA heterogeneously. On 7/14 days after the transplantation, the tumor grew approximately 7/10 mm in diameter. The single 1000 units of TNF-alpha were administrated via an internal carotid artery. 3 days after the administration of TNF-alpha, regression of the tumor size was seen in one of six rats and decrease of peritumoral edema was seen in three. These effects of TNF-alpha were, however, transient and they were not demonstrated on day 7. Single injection of TNF-alpha was not effective for large tumors more than 10 mm in diameter seen 14 days after the transplantation. These data suggest that intra-arterial TNF-alpha should be administrated at an early stage of the tumor growth and several injections are needed to cause regression in the size of the gliomas.

Animals↗

Novel cell-surface Ag expressed on rat osteoclasts regulating the function of the calcitonin receptor.

Osteoclasts are known to be hematopoietic in origin. However, the detailed mechanisms of their differentiation and activation are not known. Cell-surface molecules preferentially expressed on cells of the osteoclast lineage may play some important roles in these processes. We prepared a mAb that recognizes a unique cell-surface membrane protein specifically expressed on rat osteoclasts. Expression of this Ag, designated as Kat1 Ag, was markedly stimulated by a factor secreted by the osteoblastic cell line ROS 17/2.8. Binding studies of 125I-labeled calcitonin (CT) showed that the Ag was not the CT receptor (CTR). However, interestingly, studies of the biologic activity of this mAb that recognizes Kat1-antigen (mAb Kat1) revealed possible regulatory functions of this Ag in osteoclasts. Firstly, mAb Kat1 significantly elevated the binding affinity of the CTR expressed on osteoclast-like cells without altering the number of receptors. Secondly, CT-sensitivity of the osteoclast progenitor cells in the system of osteoclast differentiation showed marked augmentation on treatment of these cells with this mAb. Even a very low concentration of CT (0.1 ng/ml) significantly inhibited osteoclast differentiation in the presence of mAb Kat1, whereas a higher concentration of CT (10 ng/ml) was required to inhibit their differentiation in the absence of this mAb. Thirdly, mAb Kat1 inhibited dentin-resorbing activity of osteoclast-like cells. Furthermore, the inhibitory effects of CT on osteoclast-mediated dentin resorption was augmented by the presence of this mAb. These observations strongly suggest that Kat1-antigen is a unique cell-surface protein regulating the affinity of the CTR expressed on osteoclasts and also the bone-resorbing function of these cells.

Animals↗

Effects of peripheral axotomy of the inferior alveolar nerve on the levels of neuropeptide Y in rat trigeminal primary afferent neurons.

The effects of peripheral axotomy of the inferior alveolar nerve (IAN) on the presence and distribution of neuropeptide Y (NPY)-like immunoreactivity (IR) in the trigeminal sensory nuclear complex (TSNC) and trigeminal ganglion were investigated in the rat by immunohistochemistry. In the normal trigeminal ganglion, there were no NPY-IR cells, and some perivascular nerve fibres exhibited NPY-IR. In normal TSNC, many NPY-IR axons and nerve terminals were observed in the superficial layers of the subnucleus caudalis (SpVc) and paratrigeminal nucleus (paraV), but were sparse in the other subnuclei of the TSNC. Fourteen days following peripheral axotomy of the IAN, many large- and medium-sized cells in the trigeminal ganglion displayed NPY-IR, and marked increases in the numbers and staining densities of NPY-IR were observed in deeper laminae (laminae III-V) of the dorso-medial region of the SpVc and other nuclei, in addition to the dorso-medial region of the spinal trigeminal tract. Degrees of alterations of the levels of NPY were most marked in the SpVc. The present results indicate that peripheral axotomy of the IAN evokes the appearance of NPY-IR in the trigeminal ganglion and alterations of NPY-IR in the entire IAN projection areas of the TSNC.

Animals↗

Effects of sympathectomy on the cutaneous temperature abnormalities in rats with chronic constriction injury of the sciatic nerve.

Effects of surgical sympathectomy on the cutaneous temperature abnormalities of plantar surface evoked by the chronic constriction injury (CCI) of the sciatic nerve were investigated in the rat. In normal animals, there were very small temperature differences between both plantar surfaces. There were also very small temperature differences in plantar surfaces following the sympathectomy prior to CCI. In rats with CCI, the cutaneous temperature of the nerve-injured plantar surface was significantly higher (warmer) than that of the contralateral plantar surface during the first week following CCI, and then became lower (cooler). Surgical sympathectomy prior to and just after CCI significant suppressed the temperature abnormalities during the first week, but no effect was observed after 2 weeks following CCI. These observations indicate that sympathetic vasoconstriction may contribute to the cutaneous temperature abnormalities evoked by CCI during the early stage, but does not affect the abnormalities at later stages.

Animals↗

A novel monoclonal antibody recognizing a unique antigen of rat osteoclasts induced by the calcified matrices.

The morphology of osteoclasts, primary cells that resorb bone, is well documented; however, the precise details of their terminal differentiation remains obscure. To date, the only morphological criterion for identifying activated functional osteoclasts has been the presence of ruffled borders. We have developed a rat bone marrow culture system in which osteoclast-like cells formed. These cells fulfilled most of the criteria of osteoclasts, and when they were reseeded on calcified tissue, formed numerous resorption lacunae in vitro. To find an immunological marker for functional osteoclasts, we have used these cells in a functional state as antigens for the preparation of monoclonal antibodies (mAb) that reacted with rat osteoclasts; we obtained mAb Ch1 and Ch2. Interestingly, these mAbs reacted with the marginal portion of authentic osteoclasts, where they attached to the bone surface on frozen sections. The reactivity of Ch1 to rat osteoclasts was more restricted than that of Ch2: Ch1 reacted with few tartrate-resistant acid phosphatase (TRAP)-positive cells on a culture plate. These TRAP-positive cells (including mono- and multinucleated cells) were, however, converted to Ch1-positive cells when they were reseeded on calcified tissues. These findings suggested that the antigen recognized by the Ch1 antibody was induced by some factors of matrix proteins released from calcified tissues.

Acid Phosphatase↗

MRI of pituitary adenomas: the position of the normal pituitary gland.

The position of the normal pituitary gland, assessed using gadolinium - enhanced MRI was compared with the position found at surgery for pituitary adenoma in 25 patients. The tumours were five microadenomas and 20 macroadenomas. Using T1-weighted imaging, the anterior lobe could be differentiated on the sagittal image in five patients (20%) and on the coronal image in four (16%). The high intensity of the posterior lobe could be differentiated using T1-weighted sagittal imaging in 13 patients (52%). The normal pituitary gland, which enhanced more strongly than tumour, could be differentiated using Gd-DTPA-enhanced MRI on the sagittal images in 22 cases (88%) and on the coronal image in 17 (68%). In seven patients, the normal pituitary gland surrounded the tumour; it was displaced superiorly in 14 cases and superioposterorly in two but in no case was it displaced anteriorly or downwards.

Adenoma↗

Displacement of the normal pituitary gland by sellar and juxtasellar tumours: surgical-MRI correlation and use in differential diagnosis.

We compared the position of the normal pituitary gland as estimated by gadolinium (Gd)-DTPA-enhanced MRI, with its position at surgery in 40 patients with intra- and juxtasellar tumours: 22 pituitary adenomas, 4 craniopharyngiomas, 7 meningiomas, 2 germinomas, and 5 Rathke cleft cysts. In 37 of these, the normal gland showed more intense contrast enhancement than the adjacent tumour, from which it could be differentiated by Gd-DTPA-enhanced MRI, especially in the sagittal plane. The direction of displacement of the normal pituitary gland correlated well with tumour type, so that its position proved helpful in the differential diagnosis. The normal gland was typically displaced superiorly by pituitary adenomas, inferiorly by craniopharyngiomas, and anteriorly by germinomas. It showed variable displacement by Rathke cleft cysts, and was not usually displaced by meningiomas.

Adenoma↗

O6-alkylguanine-DNA alkyltransferase activity of human malignant glioma and its clinical implications.

Activity of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) is an important determinant of responsiveness of tumor cells to chloroethylnitrosoureas (CENUs), representative chemotherapeutic agents for primary malignant gliomas. In order to assess the real states of this repair protein in human malignant gliomas, we assayed AGT activity in surgically extirpated 42 malignant glioma samples and studied the distribution of the activity under certain clinical conditions. There were wide variations in AGT activity between individuals. No significant difference in AGT activity on average was seen either between glioblastoma and anaplastic astrocytoma, nor between primary and recurrent tumors. Among 42 malignant gliomas, 7 samples (16.7%) had low AGT activity less than 0.1 pmoles/mg protein. In the case of glioblastoma, tumors possessing higher AGT activity tended to be less responsive to post-operation remission-induction therapy including CENUs. The result of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) chemosensitivity assay by using the corresponding surgical specimens suggested a close relationship between cellular resistance to CENUs and AGT activity. It was found to be unlikely that a short term administration of CENUs had a significant effect on AGT activity of brain tumors in human body. We could detect a bit of definite evidences of the relevance of AGT to resistance to CENUs and need to conduct further investigations for other resistance factors.

Astrocytoma↗

Growth inhibition of subcutaneously transplanted human glioma by transfection-induced tumor necrosis factor-alpha and augmentation of the effect by gamma-interferon.

Using subcutaneous solid tumors produced by U251-MG human glioma cells, we studied the in vivo transfection of the cells with the tumor necrosis factor-alpha (TNF-alpha) gene delivered by means of liposomes. When the tumor had become 7 mm in diameter, liposomes with entrapped TNF-alpha gene were injected into the center of the subcutaneous tumor. We found that mRNA of transfection-induced TNF-alpha, which was expressed in the tumor tissue, was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) method and its protein was demonstrated by enzyme-linked immunoassay. Growth of the tumor was inhibited when the injection was carried out five times at every other day. The growth-inhibitory effect by transfection-induced TNF-alpha was much remarkable as compared with exogenous TNF-alpha and the effect was enhanced by the intraperitoneal injection of gamma-interferon (IFN-gamma) 12 h prior to intratumoral injection of the liposomes.

Animals↗

Combined antitumor effects of TNF and G-CSF on a human medulloblastoma xenograft line.

The antitumor effects of TNF and G-CSF on a xenograft line of human medulloblastoma were examined. (Method):1) A human medulloblastoma xenograft line was transplanted into nude mice. Tumor bearing nude mice were divided into the following eight groups: untreated controls (C); those receiving a subcutaneous injection of G-CSF for one week (G1); for four weeks (G2); those receiving an intratumoral injection of TNF for four weeks (Tit); an intravenous injection of TNF (Tiv); those receiving a combination of G1 and Tit (G1 + Tit); a combination of G2 and Tit (G2 + Tit); and a combination of G2 and Tiv (T2 + Tiv). The relative tumor weight in each group was calculated and any antitumor effects were examined by calculating a tumor growth inhibition ratio. 2) Tumor bearing nude mice were divided into the following two groups: those receiving a subcutaneous injection of G-CSF and an intravenous injection of TNF (G+T); and only an intravenous injection of TNF (T). We evaluated the pathological findings from the tumors at 0 h, 0.5 h, 1 h, 3 h, 6 h, 12 h, 24 h and 48 h after the TNF injection. Routine H.E. staining and immunostaining using antigranulocyte and antimacrophage antibodies were performed. (Results): 1) The tumor growth inhibition ratio was 0.112, 0.190, 0.287, 0.451, 0.347, 0.635, and 0.622 at G1, G2, Tit, Tiv, G1 + Tit, G2 + Tit, G2 + Tiv group. A combined antitumor effect was clearly seen in the G2 + Tit and the G2 + Tiv groups. 2) The tumor was fragmented by the infiltration of many inflammatory cells 24 hours after TNF injection. Many more macrophages were observed in the tumors of G+T mice than in the T mice. Granulocytes were observed only in the tumors of the G+T mice.

Animals↗

In vitro chemosensitivity test of human brain tumors using a three-dimensional organ culture with a collagen gel matrix.

We evaluated the usefulness of an in vitro tumor organ culture system using a specialized collagen gel matrix derived from pig skin as a chemosensitivity test for human brain tumors. Two xenograft tumors derived from human glioblastoma and medulloblastoma were examined with this system and the results were compared with data obtained from a nude mouse assay. Xenograft tumors exhibited in vivo-like three-dimensional growth on the collagen gel matrix and had increasing incorporation of tritiated (3H)thymidine for 2 weeks. Drug sensitivity, as measured by this assay at therapeutic peak plasma concentrations of anticancer drugs, corresponded with that measured with the nude mouse assay. Chemosensitivity of 16 surgical specimens of malignant brain tumors were also examined successfully by this collagen gel matrix (CGM) assay. When the highest inhibition rate in dose-inhibition curve was equal to or greater than 50%, the tumor was regarded to be sensitive to the agent. The efficacy rates in CGM assay for 16 lesions were 25.0% (4/16) for ACNU, 67.8% (11/16) for adriamycin, 31.3% (5/16) for cisplatin, and 67.8% (11/16) for etoposide. The CGM assay has advantages as a chemosensitivity test because of its simple procedure, rapidity, high rate of evaluable tumor growth, and in vivo-like three dimensional tumor growth. Our results indicate that the CGM assay is feasible to test the chemosensitivity of malignant brain tumors.

Animals↗