Trisomy 11 in nonlymphocytic neoplasia.
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Biomedical subjects
Publications and source records attributed to M Fukui.
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Complementary DNA clones of a putative transforming gene were isolated from NIH 3T3 cells transformed with human Ewing sarcoma DNA. The gene was termed B-raf because it is related to but distinct from c-raf and A-raf. It appears that substitution in the amino-terminal portion of the normal B-raf protein confers transforming activity to the gene.
Of 22 patients with spasmodic torticollis, 7 were treated by microsurgical decompression of the 11th nerve. In these patients, there was an intermittent horizontal torticollis characterized by aggravation of the symptoms when in a resting posture, presenting with a striking contrast to the torticollis of extrapyramidal origin that was alleviated while in the resting posture and aggravated by postural stress. A tight neurovascular contact was observed at the C1 level, occurring between the principal 11th nerve and the vertebral or posterior inferior cerebellar artery. Nerve decompression was achieved in 2 by transposing the compressing artery and in 5 by sectioning at C1 or C2 the branching root of the 11th nerve that had caused the tight cross contact by locking the nerve trunk to the dura mater. The symptoms had improved after an interval of 1 to 4 weeks. After an average follow-up of 3 years, full or satisfactory relief had been obtained in 5 and some improvement had occurred in 2 patients. Possible neural mechanisms related to torticollis of 11th nerve origin are discussed.
Immunocytochemical characterization of choroid plexus neoplasms was performed in seven cases, five being of benign choroid plexus papilloma (CPP) and the other two of malignant choroid plexus papilloma (choroid plexus carcinoma CPC). Immunohistochemical examination was performed with antibodies to glial fibrillary acidic protein (GFAP), S-100 protein, prealbumin, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and gamma-enolase. All of the five CPPs were positive for GFAP, S-100, prealbumin, and gamma-enolase; and four of them were positive for EMA. None of the CPPs was positive for CEA. Both of the two cases of CPC were positive for gamma-enolase, and one was positive for GFAP, S-100, EMA, and CEA. No CPC showed positivity for prealbumin. This report is the first to describe the usefulness of prealbumin reactivity for histological diagnosis of choroid plexus papillomas.
Immunohistochemical characterization of 14 cases of intracranial cysts was performed. Among these 14 cases, five different types of cysts were represented; Rathke's cleft cyst (4 cases), neurenteric cyst (2 cases), colloid cyst (1 case), choroidal epithelial cyst (2 cases) and arachnoid cyst (5 cases). Immunohistochemical evaluation utilized antibodies to glial fibrillary acidic protein (GFAP), S-100 protein, prealbumin, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA). GFAP-positive cells were detected in 1 Rathke's cleft cyst and in 1 choroidal epithelial cyst. S-100-positive cells were detected in 2 Rathke's cleft cysts, in 2 neurenteric cysts, in 1 colloid cyst, and in 2 choroidal epithelial cysts. Prealbumin-positive cells were detected only in the 2 choroidal epithelial cysts. CEA-positive cells were detected in 1 Rathke's cleft cyst and in 2 neurenteric cysts. EMA-positive cells were detected in all cases. Immunohistochemical study of prealbumin and S-100 protein is useful for correct diagnosis of choroidal epithelial cyst and study of CEA is useful for diagnosis of neurenteric cyst. The arachnoid cyst is negative for immunoreactivity to GFAP, S-100, prealbumin, and CEA; this can be helpful in distinguishing this type of cyst from single epithelial cysts, a task that is sometimes difficult with only light microscopy.
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The clinical and pathological features of six patients with so-called "intraventricular oligodendroglioma" are reported. The tumor had no predilection for sex, and the patients' age at diagnosis ranged from 15 to 39 years. The lesions were located in the lateral and/or third ventricles. Total removal of the tumor was performed in three patients, and the remaining three underwent partial resection. Postoperative irradiation was given to five patients. A follow-up study revealed that five patients were free of recurrent tumor at 15 to 227 months after treatment, and one was alive with disease 25 months after surgery. Histologically, all tumors were composed of small uniform cells, with perinuclear halos and regular round nuclei. Tumor cells were sometimes arranged around nucleus-free fibrillary zones. Mitoses were infrequent. Ultrastructurally, neoplastic cells had round nuclei with dispersed heterochromatin and organelle-sparse cytoplasm containing occasional microtubules, 20 to 25 nm in diameter, and scattered dense-core vesicles, 100 to 200 nm in diameter. Cell processes containing dense-core and clear vesicles were frequently present. Thus, these neoplasms should be considered neuronal in origin, and should be classified as "intraventricular neurocytomas."
The physical act of operating on 13 patients with meningiomas was studied for its effect on the fibrinolytic system. Fibrinolytic abnormalities, mainly due to an increase of plasma fibrinolytic activity, appeared in three patients prior to, during, or after surgery. These patients demonstrated hemorrhagic diathesis in the operative wounds which was associated with a consumptive coagulopathy, namely, an increase of fibrin/fibrinogen degradation product concentration and a decrease of fibrinogen concentration in plasma. Antiplasmin agents (gabexate and tranexamic acid) were effective in minimizing loss of blood during and after the operation. Abnormal hyperfibrinolysis seems to play a role in hemostatic difficulties in patients undergoing surgery for meningioma.
Relationship between angiographical manifestations and operative findings of hemifacial spasm was studied in 100 cases. Vertebral angiography was performed, and Towne, straight AP, and lateral projections were routinely studied. The anterior inferior cerebellar artery (AICA) directly compressed the facial nerve root exit zone in 54 instances, the posterior inferior cerebellar artery (PICA) in 38, and the vertebral artery (VA) in 11. Compressions by multiple vessels were observed in 3 cases. Anatomical variations of the AICA and the PICA were classified into 3 groups according to their origins and their distributions of blood supply: Type I, normal distribution of AICA and PICA; Type II, common trunk anomaly with dominant AICA (basilar artery origin); and Type III, common trunk anomaly with dominant PICA (vertebral artery origin). In our cases, 35% of them showed normal distribution, 34% dominant AICA, and 35% dominant PICA. Analyses of the angiograms revealed significantly increased numbers of common trunk anomalies when compared with normal angiograms studied by Takahashi. In 60 of the 65 cases with common trunk anomalies, facial nerves were compressed by the main trunk or the branches of the dominant artery. There were 35 cases which belonged to Type I anatomical classification. They were subdivided into 2 groups according to the size of the AICA and PICA: 1. AICA greater than PICA, and, 2. PICA greater than AICA. In the AICA greater than PICA subgroup, the AICA was the offending artery in all but one case. In the PICA greater than AICA subgroup, the PICA was responsible in 9 of 17 cases. In 31 cases, angiograms showed a redundant VA with lateral elongation into the cerebellopontine angle.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of intracarotid hyperosmolar mannitol on the blood-brain barrier (BBB) in triethyl tin (TET)-induced rat brain edema was examined by using intravenous Evans blue (EB, MW 68,000) and Adriamycin (ADM, MW 580) as tracers. Three ml of 1.4 M mannitol solution were administered through the right carotid artery during 45 s for BBB opening. The barrier was opened for 60-120 minutes and then re-established. The reversibility was preserved in TET-treated rats and controls. In fact, the intravenous injection of EB stained both TET-treated and non-treated cerebral hemispheres with mannitol-induced transient BBB disruption, but not without BBB disruption. BBB was resistant to both high and low molecular weight substances in TET-induced edema. The importance of this hyperosmotic studies provides the evidence for normal BBB function in TET-induced brain edema.
Neurotoxicity of adriamycin (ADM) was investigated following the transient disruption of the blood-brain barrier (BBB) in rats. The BBB disruption by the hyperosmotic agent (1.4 M mannitol) was confirmed by the leakage of ADM and Evans blue administered intravenously. Neuropathological changes due to the toxicity of ADM were found as early as day 4. The neurons in the cerebral cortex and nucleus caudatus-putamen showed focal clearing of the nuclear chromatin, increased dense bodies in the cytoplasm and dilatation of the cisternae of the rough endoplasmic reticulum (r-ER) and Golgi apparatus. By day 7, nucleolar segregation and irregular membranous structures appeared in the nuclei with the progression of cytoplasmic changes. By day 10, the cytoplasm of many neurons was vacuolated. Electron-microscopically, the cisternae of the r-ER and Golgi apparatus were prominently dilated in these neurons. Neuronal microtubules were increased in number, in particular in the perinuclear region. Numerous whorl-like membranous structures and separation of nuclear membrane were also observed. Some astrocytic processes surrounding the blood vessels revealed loss of organelles and a few pericytes showed an increased number of lysosomes on days 7 and 10. This experiment clearly demonstrates that ADM has strong neurotoxic effects in the central nervous system when the BBB is disrupted, and provides the warning for the possibilities of neurotoxic side effects when ADM is administered, in combination with a hyperosmotic agent, for the treatment of human malignant tumors, including brain tumors.
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The metabolism of benoxinate hydrochloride [2-(diethylamino)ethyl 4-amino-3-butoxybenzoate monohydrochloride; oxybuprocaine] was examined in humans after administration of a single oral dose. The drug was almost completely absorbed and was rapidly excreted in the urine (92.1% of dose in 9 h). Nine metabolites and unchanged drug were isolated from the urine and identified by comparison of TLC, GC, and GC-MS with authentic compounds. Any metabolites reflecting initial loss of the butyl side chain of benoxinate could not be detected. This suggests that the ester portion is metabolized more rapidly than the O-butyl side chain. 3-Butoxy-4-aminobenzoic acid, the hydrolyzed product of benoxinate, was primarily excreted (70-90% of dose) as the glucuronide together with a trace of the glycine conjugate (0.35% of dose). In addition, 3-butoxy-4-acetylaminobenzoic acid, 3-hydroxy-4-aminobenzoic acid, and 3-hydroxy-4-acetylaminobenzoic acid were identified, the latter two being detected partly as the glucuronides (1.20 and 1.43% of dose, respectively).
Immunohistochemical stains using neuronal and glial marker proteins were applied to retinoblastomas tissues from 14 children. Among the neurofilament triplet proteins, NF68Kd positive cells were observed in 12. Few NF160Kd positive cells were noted in 2, and NF210Kd positive cells were not detected. The positive ratio of NF68Kd and gamma-enolase seems to relate to the Flexner-Wintersteiner rosettes. Gamma-enolase positive cells were observed in 13. The distribution in tumor tissues was broader than that of NF68Kd positive cells. The immunoreactivities of NF68Kd were in parallel with those of gamma-enolase. Few GFAP positive cells were present around blood vessels, while S-100 protein and MBP positive cells were never observed. Our results indicate that retinoblastoma possesses predominantly neuronal properties, albeit in an immature form.
CT findings of 6 cases with germinoma originating in the basal ganglia and thalamus are reported. The early finding of germinoma in this region on plain CT, was an irregularly defined, slightly high density area without mass effect. Repeated CT scanning showed enlarging iso-density lesion accompanied by mass effect to high. Intratumoral cysts and calcifications were frequently observed. The tumor showed mild to moderate and inhomogeneous enhancement by intravenous injection of contrast medium. A tendency to ipsilateral hemicerebral atrophy was found in one case. These findings were somewhat different from those of germinomas in the pineal and suprasellar regions. This phenomenon may be related to the anatomical difference of the brain where the tumor originated.