[Surgery in the anterior skull base and its reconstruction].
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Bone Transplantation↗
Biomedical subjects
N Arita
Publications and source records attributed to N Arita.
Characteristics of MHC antigen expression and tumor-infiltrating mononuclear cells in renal cell adenomas and carcinomas.
We compared the expression of major histocompatibility complex (MHC; HLA class I and II) antigens and the presence of tumor-infiltrating mononuclear cells presenting S100 protein (S100), CD68 antigen, or CD45RO antigen in formalin-fixed, paraffin-embedded tissue sections of 10 renal cell carcinomas and 9 renal cell adenomas using immunohistochemistry. The expression of beta 2-microglobulin (B2MG) as an HLA class I antigen in all 10 cases (100%) and that of HLA-DR/alpha as an HLA class II antigen in 7 of 10 cases (70%) of carcinoma was stronger than that in the adjacent proximal convoluted tubule, but was respectively not different to weaker in 8 of 9 cases and not different to markedly weaker in all cases of adenoma. Furthermore, there was comparatively dense infiltration by S100(+) antigen-presenting cells in the carcinomas, but almost none in the adenomas and generally dense infiltration by CD45RO(+) T cells and CD68(+) macrophages in the carcinomas, but little to none in the adenomas. We concluded that the generally enhanced expression of MHC antigens in carcinomas must be an immunophenotypic deviation from not only the adjacent proximal convoluted tubule but also adenomas, and that the predominant infiltration of antigen-presenting cells, T cells and macrophages in the carcinomas, but not in the adenomas, reflects the anti-cancer immune reaction.
Adenoma↗
Pharmacokinetics of intrathecal 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride in rats.
The pharmacokinetics of intrathecal 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) were studied in female Wistar rats by macroscopical autoradiography using 14C labeled ACNU. In normal rats, ACNU rapidly distributed in the subarachnoid space and ventricles after intracisternal administration. Diffusional transport into the brain tissue was limited to a depth of 1 or 2 mm from the cerebrospinal fluid (CSF) surface of the brain. Clearance of ACNU from the CSF space and brain was relatively fast and the half time of ACNU concentration at the cortical or ventricular surface was 10 min. In rats with leptomeningeal tumor induced by intracisternal inoculation of Walker 256 carcinosarcoma cells, the distribution pattern of ACNU after intracisternal administration was essentially the same as in normal rats until the tumor had grown in the subarachnoid space to form more than 10 or 20 layers of tumor cells. ACNU was distributed in the tumor as well. When the tumor had grown to form masses in the subarachnoid space, ACNU failed to penetrate to more than a depth of 1 or 2 mm from the tumor surface. Our results suggest that intrathecal ACNU administration may have no, or minor side effects on the brain and that it can eliminate floating or thin layered tumor cells in the subarachnoid space but not bulky tumors.
Animals↗
Anti-proliferative effects of TNP-470 on human malignant glioma in vivo: potent inhibition of tumor angiogenesis.
A novel angiogenesis inhibitor TNP-470 was investigated for its anti-tumor activity against malignant gliomas both in vitro and in vivo. TNP-470 cytostatically inhibited the growth in all of the seven glioma cell lines in culture including anticancer drug resistant cells. The 50% inhibitory concentrations (IC50) of these glioma cell lines were 10 to 30 micrograms/ml and they were 10 to 20 times higher than IC50 of normal endothelial cells. TNP-470 (30 mg/kg, i.p., every other day) also significantly inhibited the tumor growth of T98G-transplanted nude mice. Microscopically, tumor vessels after the treatment of the tumor-bearing mice with TNP-470 became fewer in number and smaller in diameter than those without treatment. Furthermore, there appeared extensive necrotic areas in the tumor with TNP-470. These results indicate that TNP-470 is a potent angiogenesis inhibitor for malignant gliomas. In addition, the studies of labeling index of BrdU and Ki67 suggest that TNP-470 may act mainly on tumor endothelial cells, thus resulting in reduction of the tumor growth.
Animals↗
Leptomeningeal dissemination of malignant gliomas. Incidence, diagnosis and outcome.
To understand the clinicopathology features of leptomeningeal dissemination of malignant gliomas, a total of 157 consecutive patients treated between 1978 and 1989 were analysed. Twenty-two patients (14%) were judged to have dissemination. In 20 patients, the dissemination was diagnosed antemortem. Eleven patients had neurological deficits due to dissemination, whereas the other 9 without these had CT or myelographic evidence of dissemination. The peak incidence of dissemination was seen in the first and second decades of life. The mean age of 22 patients with dissemination was 31 years, significantly lower than that (44.5 years) of patients without dissemination. Fifteen patients developed dissemination within one year after diagnosis (early dissemination), 60% of them were less than 30 years of age. All patients with late dissemination (more than one year after diagnosis) underwent a second craniotomy for tumour removal before dissemination, while none of the 15 patients with early dissemination did. Survival after diagnosis in patients with dissemination was shorter, although statistically not significant, than that of patients without dissemination. Survival after dissemination was limited in all patients (mean 19 weeks, range 2-39 weeks). Immunohistochemical study revealed that the disseminated tumour expressed less glial fibrillary acidic protein than the primary tumour. Our results suggest that dissemination does not seem to result from extended survival of the patients, but may occur at any time in malignant gliomas. Some malignant gliomas, especially in younger patients, have a capability to acquire biological characteristics suitable for dissemination in the earlier stage of the disease.
Adolescent↗
Expression patterns of messenger ribonucleic acids encoding prohormone convertases (PC2 and PC3) in human pituitary adenomas.
OBJECTIVE: Prohormone convertases (PC2 and PC3) have been reported to play an important role for prohormone processing in rodent pituitaries. However, expression of mRNAs encoding these enzymes has not been characterized in human pituitaries. In addition, altered or insufficient prohormone processing has been reported in some human pituitary adenomas. Thus, the expression patterns of these mRNAs in non-tumorous and tumorous human pituitaries should be examined. DESIGN: Total RNAs were extracted from non-tumorous or tumorous human pituitaries to analyse PC2 and PC3 mRNA expression. SAMPLES: Five ACTH producing adenomas, 11 GH producing adenomas, one PRL producing adenoma and five non-functioning adenomas were obtained at surgery. Two non-tumorous pituitaries were also included in this study. MEASUREMENTS: The contents were quantitatively measured by Northern blot analysis using rat PC3 cDNA or human PC2 cDNA as a probe. The method was also developed for the detection of PC2 mRNA by Southern blot analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products. RESULTS: PC2 and PC3 mRNAs in non-tumorous samples were detected by Northern blot analysis whereas their contents in tumorous samples varied from high levels to undetectable. Marked variation of PC3 mRNA levels was observed among GH producing adenomas. ACTH producing adenomas were observed to express PC3 mRNA. Northern blot analysis also revealed that PC2 mRNA levels in ACTH producing adenomas were low except for one sample. PC2 mRNA expression in GH producing adenomas was confirmed by Southern blot analysis of RT-PCR products. This procedure also confirmed the various levels of PC2 mRNA expression among ACTH producing adenomas. CONCLUSION: The expression of PC2 and PC3 mRNA in human pituitaries has been confirmed. However, their expression has been observed to vary quantitatively and not to be restricted to certain types of pituitary cells.
Adenoma↗
Effects of therapy on anterior pituitary functions in patients with primary intracranial germ cell tumor.
Intracranial germ cell tumors are known to be frequently associated with anterior pituitary hypofunction and diabetes insipidus. In general, these manifestations are not ameliorated even after successful radiotherapy. Since platinum based chemotherapy is introduced as a therapeutic approach to these tumors, its effectiveness is compared with the outcome obtained by radiotherapy in terms of tumor regression and endocrine functions. In this study, six patients received conventional radiotherapy and one received chemotherapy as an initial treatment. In all patients, complete remission was achieved irrespective of the therapeutic method. Their diabetes insipidus was not improved. Many patients treated with radiotherapy did not show the complete improvement of pre-existing hypofunction of the anterior pituitaries. In contrast, chemotherapy achieved almost complete hormonal remission. These clinical observations suggest that chemotherapy is quite effective in oncological as well as endocrinological aspects in treating intracranial germ cell tumors.
Adolescent↗
Multiple ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum. A histochemical and immunohistochemical study.
An unusual case of multicentric ileal carcinoids and appendiceal endocrine carcinoma in association with Meckel's diverticulum was studied, with special attention given to the histogenesis of these neoplasms. A total of six ileal carcinoids, the largest of which was located in the wall of Meckel's diverticulum, were macroscopically and microscopically confirmed to be multicentric and revealed no visceral metastases. The histochemical and immunohistochemical profiles of the ileal carcinoids and the appendiceal carcinoma differed considerably: the former resembled subepithelial neuroendocrine cells and the latter resembled epithelial nonmucous cells and Paneth cells. The appendiceal carcinoma exhibited signs of endocrine differentiation, expressing somatostatin and vasoactive intestinal polypeptide, and secreted mucus. The tumor had metastasized to various organs. The carcinoids exhibited signs of neuroendocrine and glandular differentiation, expressing neuron-specific enolase, serotonin, chromogranin A, and endocrine granule constituent, and secreted little mucus. The data suggest different tumor cell origins or different grades of differentiation of the two types of intestinal endocrine cell tumor.
Aged↗
[Long survival after removal of a huge brain tumor which had metastasized from a lung cancer: case report].
Patients with large metastatic brain tumors are considered to have poor prognosis. We report a case of a patient with more than 33 months survival after complete resection of a huge temporal tumor which had metastasized from a lung cancer. A 57-year-old woman presented left hemiparesis and disturbance of consciousness. Magnetic resonance images revealed a huge cystic mass lesion in the right temporal lobe. After a macroscopically complete excision of the tumor, she received radiation therapy (whole brain 50 Gray). She had received lung surgery for the primary lung cancer, 2 years prior to brain metastasis. Histological examination showed papillary tubular adenocarcinoma which was similar to the previously resected lung cancer. Thirty three months after the resection of the intracranial tumor, she has no neurological deficits and no signs of recurrence of either brain tumor or lung tumor. We discuss the size of metastatic brain tumor and the postoperative prognosis of patients with metastatic brain tumor.
Adenocarcinoma, Papillary↗
Purification of motility factor (GMF) from human malignant glioma cells and its biological significance in tumor invasion.
Two molecular species of glioma-derived motility factor (GMF), GMF-I and GMF-II, have been purified to homogeneity from the serum-free conditioned medium of a highly invasive human glioma cell line, T98G, by gelatin affinity chromatography and heparin affinity-, DEAE-, hydroxyapatite-, gel permeation- and sulfopropyl high performance liquid chromatography. GMF-I and GMF-II showed a single protein band on non-reducing SDS-polyacrylamide gel electrophoresis with a molecular mass of 145 kDa and 165 kDa, respectively. The physico-chemical characteristics of these two GMFs are similar with respect to amino acid composition. GMF-I and GMF-II both stimulated the migration of T98G cells in a concentration-dependent manner, and the activity of GMF-I was about 5 times as strong as that of GMF-II. Checkerboard analysis demonstrated that the GMFs had not only a chemotactic effect but also a chemokinetic effect on T98G cells. C6 glioma cells and T98G cells, both of which showed high invasiveness in an in vitro invasion assay with reconstituted basement membrane, Matrigel, migrated to the GMFs with great intensity, while A172 and 9L glioma cells and normal glial cells, all of which weakly infiltrated the Matrigel barrier, migrated to the GMFs with much less intensity. These results indicate that migratory response of glioma cells to the GMFs correlates well with invasiveness, suggesting an important role(s) of the GMFs in the process of glioma cell invasion.
Amino Acids↗
Expression of tenascin in human gliomas: its relation to histological malignancy, tumor dedifferentiation and angiogenesis.
The immunohistochemical distribution of tenascin (TN), fibronectin (FN), and laminin (LN) was investigated in 56 human gliomas (8 astrocytomas, 15 anaplastic astrocytomas, and 33 glioblastomas) with regards to the histological degree of malignancy and the degree of tumor cell differentiation evaluated by the staining of glial fibrillary acidic protein (GFAP). In 8 anaplastic astrocytomas and 28 glioblastomas, TN was predominantly immunolocalized in the basement membrane zone of the proliferating tumor vessels; sections of all astrocytomas were negative for TN staining. FN was localized in the basement membrane zone of the vessels in all astrocytomas, 12 anaplastic astrocytomas, and 22 glioblastomas. In 7 anaplastic astrocytomas and 19 glioblastomas, both TN and FN were expressed to various degrees in the tumor vessels. However, most of the TN-positive vessels did not express FN, and most of the FN-positive vessels were negative for TN staining. Furthermore, in 6 anaplastic astrocytomas and 12 glioblastomas, either TN or FN, but not both, were expressed in any area on serial sections. Most of the tumor cells around TN-positive, FN-negative tumor vessels did not express GFAP. On the other hand, GFAP was present in most tumor cells around TN-negative, FN-positive vessels. LN was detected in all vascular and pial-glial basement membrane zone of the tissues examined. These findings indicate that the degree of histological malignancy and the degree of cell dedifferentiation of human gliomas correlate well with the expression of TN, but are inversely correlated with the expression of FN.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Monoclonal↗
Pituitary granuloma and chronic inflammation of hypophysis: clinical and immunohistochemical studies.
We describe five patients with chronic inflammation of the hypophysis including three pituitary granulomas of unknown aetiology. In contrast to the previously reported cases, the involvement of neurohypophysis or hypothalamus was a distinct clinical feature in these patients. Impairment of anterior pituitary function was less prominent, while polyuria and polydipsia occurred in all cases. Enlargement of the sella turcica was absent in three and slight in two cases. CT scan and MR images demonstrated a contrast-enhanced sellar mass in all patients; abnormally thickened pituitary stalk and infundibulum with contrast-enhancement was observed in four. The fibrous tissues were removed by the transsphenoidal approach in four patients, and by the subfrontal approach in one case. In all patients, the endocrinological dysfunction was prolonged. No increase in the size of the remaining pituitary mass was demonstrated on repeated MR images in any of the patients. On histological examination, granulomatous formation was present in three samples, and multinucleated Langhans' giant cells were seen in one. The epithelioid cells and multinucleated giant cells constituting the granulomas were positive for anti-macrophage antibody. No firm laboratory or histological evidence was obtained supporting the presence of systemic disease leading to granulomas. In the other two cases, the pituitary lesions were composed of chronic inflammation tissue, and serum antipituitary antibodies were present in a patient with concurrent Hashimoto's thyroiditis. Our experiences with chronic inflammation of the hypophysis indicate that these patients are best managed by histological confirmation of the lesion followed by adequate hormonal replacement.(ABSTRACT TRUNCATED AT 250 WORDS)
Corticosterone↗
[Pharmacokinetics of MX2, a new morpholino anthracycline, in CSF following intravenous injection].
MX2 x HCl is a new morpholino anthracycline derivative with molecular weight 622.07, and highly lipophilic. In the animal experiments, MX2 was found to cross the blood brain barrier after i.v. injection. Its distribution into the brain was increased by intracarotid injection. In the present study, we examined the distribution of MX2 into the cerebrospinal fluid (CSF) after i.v. administration (5 mg/kg) in normal rabbits. Five min after injection, plasma concentration of MX2 reached to the maximum level (4344.5 ng/ml). CSF concentration of MX2 was at the highest level (75.8 ng/ml) 10 min after injection, and thereafter decreased gradually in parallel with plasma concentration. At 5 hrs after injection, CSF concentration became 26.7 ng/ml, AUC half time of elimination, and mean residence time were 3093.8 ng.hr/ml, 4.57 hrs and 5.10 hrs in plasma and 212.3 ng.h/ml, 5.23 hrs and 7.14 hrs in CSF, respectively. These results indicate that MX2 is able to distribute into CSF after i.v. injection, and expected to be a new anticancer drug for brain and leptomeningeal tumors.
Animals↗
[In vitro ENU-induced carcinogenesis of rat fetal astroglia--biological character of mutant glial cell].
To investigate glial carcinogenesis in vitro, fetal rat brain cells were cultured and exposed to ENU (approximately 200 micrograms/ml). The cells were passaged weekly thereafter. Morphological changes were observed under the phase contrast microscope. When mutant colonies where the cells lost contact inhibition and grew in a multilayer fashion appeared, the cells were cloned. To assess the biological characters of cells, expression of GFAP, vimentin, A2B5 and p53 product were determined by immunohistochemistry and flow cytometry. Tumor forming ability of the cells was evaluated by both colony forming efficiency in low serum medium (LSM; 2% FBS, 300 cells/100 mm dish) and transplantability to nude mice. Both primary cultured and ENU-treated cells were positive for GFAP and vimentin, but population of A2B5 positive cells was less than 5%, thus indicating that these cells were astroglial in origin. The mutant colonies appeared 7 weeks after ENU treatment. These cells grew rapidly with cell doubling time ranging between 18 to 26 hours, while non-ENU-treated astroglias had a longer cell doubling time (48 to 55 hours). The cloned mutant glial cell lines formed large colonies in LSM (efficiency 20-40%), but astroglial cells did not. The mutant astroglial cells also developed tumors in nude mice. p53 protein was never detected in normal astroglia, however, some glial cells treated by ENU abruptly became p53 positive after several passages. These p53 positive cells formed stratified colonies thereafter. These results indicate that mutant astroglial cells can be induced by a single dose of ENU in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Transfer of multiple sclerosis into severe combined immunodeficiency mice by mononuclear cells from cerebrospinal fluid of the patients.
To investigate the mode of the pathogenesis of multiple sclerosis (MS), we transferred cerebrospinal fluid (CSF) cells, predominantly mononuclear cells, from MS patients at both exacerbation and remission stages of the disease into severe combined immunodeficiency mice by intracisternal injection. As controls, (i) CSF cells from patients with cervical spondylosis and (ii) peripheral blood mononuclear cells from normal individuals were transferred. Four to 6 weeks after transfer, most mice transferred with CSF cells from MS patients at the exacerbation stage of the disease developed paralysis and ataxia. The histopathological examination on the sacrificed mice revealed multiple scattered, discrete lesions localized in the white matter of the brainstems and spinal cords. These lesions were characterized by various degrees of tissue necrosis, involving inflammatory-cell infiltration. Most infiltrating cells were macrophages, although a smaller number of granulocytes appeared in several foci. Reactive astrocytic gliosis was also seen around the necrotic foci. Furthermore, these lesions exhibited demyelination. These histopathological changes are similar to those seen in MS. In contrast, none of the severe combined immunodeficiency mice transferred with CSF cells from MS patients at the remission stage of the disease, or with CSF cells from the patients with cervical spondylosis, or with peripheral blood mononuclear cells from normal individuals showed any such histopathological changes. These observations provide convincing direct evidence of encephalitogenicity of mononuclear cells in CSF from MS patients at the exacerbation stage of the disease.
Animals↗
Identification and characterization of high molecular weight forms of basic fibroblast growth factor in human pituitary adenomas.
Basic fibroblast growth factor (bFGF) extracted from 23 human pituitary adenomas and 2 nontumorous anterior pituitary glands was examined by Western blot analysis to elucidate their molecular forms. Four bands that specifically interacted with anti-bFGF antibody were identified at the regions of 16K, 18K, 22K, and 24K mol wt. These immunodetectable bFGFs were bound to a heparin-Sepharose affinity column and eluted with 1-2 M NaCl. These partially purified tumor extracts could stimulate dose-dependently the growth of FGF-responsive cells. Some tumors contained bFGF with a mol wt of 24 K as a dominant form. In contrast, a major form of bFGF at the region of 18K was identified in the nontumorous anterior pituitary glands. We also addressed the possible presence of FGF receptor mRNA using Northern blot analysis. Many, but not all, human pituitary adenomas were found to contain detectable levels of FGF receptor mRNA with a size of 3.5 kilobases. The present results suggest that the role of bFGF in growth and hormone secretion in human pituitary adenomas should be examined using high mol wt forms of bFGF.
Adenoma↗
Intracranial and intraspinal dissemination of an ACTH-secreting pituitary tumor.
A case of a 29-year-old man with an ACTH-producing pituitary tumor disseminated into the subarachnoid space is described. After total adrenalectomy for Cushing's disease at the age of 15, Nelson's syndrome developed. Transsphenoidal adenomectomy at 17 and 21 years of age, pituitary irradiation and medical therapies with sodium valproate, baclofen and bromocriptine failed to lower his plasma ACTH level. Multiple intracranial and intraspinal tumors associated with the symptoms of left hemiparesis developed. The removal of a tumor grown at the level of C1-3 was performed with successful palliation of his symptoms. Histologically, the tumor cells showed sinusoidal, papillary and diffuse patterns with a preponderance of the former over the latter two, although the papillary pattern predominated in the primary pituitary tumor. Immunohistochemical analysis demonstrated most cells to be positive for ACTH in the metastatic tumor as well as the primary adenoma. The clinical significance of his course is discussed with a review of 11 reported cases with metastatic ACTH-producing pituitary tumors.
Adrenocorticotropic Hormone↗
[A case of recurrent malignant glioma treated by superselective intraarterial chemotherapy with a combination of etoposide and cisplatin].
Superselective intraarterial infusion of etoposide and cisplatin was performed in a patient with recurrent malignant glioma located in the left midbrain extending to thalamus which had progressed after two courses of radiotherapy and chemotherapy with various anticancer agents. Infusion of etoposide (80 mg/m2) and cisplatin (80 mg/m2) at the basilar top did not result in any neurological deficits when infused for 60 minutes with intermittent infusion of papaverine and nicardipine. CT scan carried out 6 days after chemotherapy demonstrated disappearance of the tumor.
Antineoplastic Combined Chemotherapy Protocols↗