Autoradiographic Analysis of Radiolabeled Anti-carcinoembryonic Antigen Monoclonal Antibody CEA102 in Colorectal Cancer Using Computed Radiography

Anti-carcinoembryonic antigen monoclonal antibody (MAb) CEA102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with ¹³¹I-labeled intact CEA102 or its F(ab')₂. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of ¹³¹I-labeled CEA102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of administered radiolabeled MAb in individual tumors, but the density of the tumors was higher than that of the normal tissues. In the quantitative distribution analysis of CEA102, the uptake of the primary tumor (mean 1.10%ID/kg) was ten-fold greater than that of the normal colon mucosa (mean G.10%ID/kg). These results revealed that the application of MAb has great potential in radioimmunodetection as well as in antibody-directed therapy.     

K-Ras gene status and expression of Ras/mitogen-activated protein kinase (MAPK) signaling molecules in ameloblastomas

BACKGROUND: To clarify the roles of rat sarcoma (Ras)/mitogen-activated protein kinase (MAPK) signaling pathway in oncogenesis and cytodifferentiation of odontogenic tumors, K-Ras gene status and expression of Ras, Raf1, MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK)1, and ERK1/2 proteins were analyzed in ameloblastomas as well as in tooth germs. METHODS: Paraffin sections of 10 tooth germs and 46 benign and 6 malignant ameloblastomas were examined immunohistochemically for the expression of K-Ras, Raf1, MEK1, and ERK1/2. Frozen tissue samples of 22 benign ameloblastomas and 1 malignant (metastasizing) ameloblastoma were analyzed by direct DNA sequencing to detect K-Ras gene alteration. RESULTS: Immunohistochemical reactivity for K-Ras, Raf1, MEK1, and ERK1/2 was detected in both normal and neoplastic odontogenic epithelium, and these molecules were reactive chiefly with odontogenic epithelial cells neighboring the basement membrane. Plexiform ameloblastomas showed slightly stronger expression of these Ras/MAPK signaling molecules than follicular ameloblastomas. Keratinizing cells and granular cells showed decreased reactivity for the signaling molecules. Basal cell ameloblastomas showed slightly stronger reactivity for the signaling molecules than did the other subtypes. K-Ras immunoreactivity in malignant ameloblastomas was lower than that in dental lamina of tooth germs. Direct DNA sequencing showed a GGT to GCT point mutation at codon 12 of K-Ras gene in one ameloblastoma. Conclusion: Expression of K-Ras, Raf1, MEK1, and ERK1/2 in tooth germs and ameloblastomas suggests that Ras/MAPK signaling pathway functions to regulate cell proliferation and differentiation in both normal and neoplastic odontogenic epithelium. K-Ras gene status implied that K-Ras mutations might play a minor role in oncogenesis of odontogenic epithelium.     

A case of corticobasal degeneration presenting with visual hallucination]

We report a case of corticobasal degeneration (CBD) presenting with visual hallucination. A 65-year-old woman showed clumsiness of the left hand. Clinical symptoms slowly progressed to include rigidity, which was left side dominant, limb-kinetic apraxia of the left hand, disorder of construction and dressing, unilateral spatial neglect, cortical sensory loss and alien limb phenomenon. Cranial MRI showed atrophy of the parietal and medial aspect of the frontal lobes, which was more severe on the right than on the left. SPECT images showed hypoperfusion in the parietal, frontal and temporal lobes, which were similarly more severe on the right than on the left. We diagnosed the patient as having CBD based on the clinical symptoms. Two years' later, she developed recurrent visual hallucinations that were typically well formed and detailed. Since patients with CBD generally do not experience visual hallucination, this case is considered the very rare and indicates the possibility that visual hallucination may be one of the clinical symptoms of CBD.     

A case of recrudescent groove pancreatitis, which was in remission by proximal gastrectomy with vagotomy for gastric cancer]

This report describes our experience with a 60 year old male who suffered from a recrudescence of groove pancreatitis. He had been treated by conservative medication therapy by proton pump inhibitor used for therapy of duodenal ulcer, and was in remission. During a follow-up one year later, endoscopy revealed gastric cancer, for which a proximal gastrectomy and vagotomy were performed. The patient continues to remain in remission for the groove pancreatitis. Our experience with the clinical course of this disease, in which treatment for duodenal ulcer was used effectively, offers new insights into the progression and therapy of groove pancreatitis.     

Calorie restriction increases serum parathyroid hormone and decreases serum calcitonin levels in patients with maturity onset diabetes mellitus

Calorie restriction is important in managing patients with maturity onset diabetes mellitus (NIDDM). The effect of such restriction on calcium metabolism is not known. The objective of this study was to determine whether patients on calorie restricted diets would show any modification of parathyroid hormone (PTH) and calcitonin (CTN). The serum levels of PTH and CTN were measured by radioimmunoassays in 269 patients with NIDDM. The patients were divided into two groups depending on the intake of calorie, and PTH and CTN were monitored for 2 years. Plasma levels of vitamin D were measured by competitive protein binding assays before and after each program. The level of PTH (520.8±266.0 pg/ml) (mean±S.D.) was significantly (P<0.01) higher in 109 diabetic patients whose calorie intake was restricted for 2 years (diet (D) group) as compared with that (256.6±103.8 pg/ml) of 160 diabetic patients whose calorie intake was not restricted (non-diet (ND) group). The daily oral calcium intake of the two groups did not differ significantly. We found no significant difference in the serum PTH level in the ND groupVS. normal control subjects (248.8±98.4, N=78). The serum calcium concentration and the amount of calcium excreted in urine were slightly but significantly (P<0.01) lower in the D than in the ND group. The rate of tubular reabsorption of phosphate (% TRP) was significantly lower in the D group than that in the ND group (P<0.01). The serum CTN level was significantly (P<0.01) lower in the D group (33.9±11.3 pg/ml) than in the ND group (64.9±21.2 pg/ml) 2 years after each treatment. The plasma 1,25-(OH)₂-vitamin D level was significantly (P<0.01) lower in the D group (22.2±6.6 pg/ml) than in the ND group (50.6±4.2 pg/ml). When the restriction of calorie intake in the D group was canceled, their PTH levels decreased, which was accompanied by increase in the 1,25-(OH)₂-vitamin D levels, whereas their CTN levels were unchanged. These observations suggested that a restricted calorie intake is a risk factor for secondary hyperparathyroidism as well as for a low serum level of CTN in patients with NIDDM.     

A Case of Fibrous Histiocytoma Associated with Xanthogranulomatous Alteration

We report here an unusual case of fibrous histiocytoma in which an area of xanthogranuloma was observed histologically. Our case suggests that adult xanthogranuloma is a variant of fibrous histiocytoma.     

Tumor-specific binding of radiolabeled G-22 monoclonal antibody in glioma patients.

Iodine-131-labeled G-22 monoclonal antibody F(ab')2 fragment reaching specifically with a glioma-associated surface glycoprotein was administered to 12 glioma patients to investigate its use in radioimaging of intracranial gliomas. No immediate or delayed side effects were attributable to antibody injection. Nine patients received the radiolabeled complex intravenously. The images of low-grade gliomas were generally poor and disappeared within 4 days. High-contrast images were obtained beyond the 7th day in high-grade gliomas except one case in the pineal region. Three patients received intraventricular or intratumoral administration. Clear images of all tumors were demonstrated from the 2nd until later than the 7th day. One patient with cerebrospinal fluid (CSF) dissemination of brainstem glioma demonstrated negative CSF cytology after intraventricular administration.     

Direct injections of calcitriol into enlarged parathyroid glands in chronic dialysis patients with severe parathyroid hyperfunction

Summary: Severe secondary hyperparathyroidism in chronic dialysis patients has been recently treated by supraphysiological concentration of calcitriol achieved through pulse therapy. However, there are many patients resistant to this therapy, who usually have larger parathyroid gland(s). to overcome this resistance, calcitriol was injected directly into the enlarged glands under ultrasonographic guidance. We injected 70–90% of the calculated gland volume of calcitriol solution (1 μg/mL) into the glands of 7 patients three times per week for 2 weeks. the parathyroid hormone (PTH) levels decreased significantly after 2 weeks of direct injections of calcitriol. Following a further 4 weeks of calcitriol pulse therapy, PTH levels remained suppressed and serum alkaline phosphatase activity and the volume of parathyroid glands also decreased. During the long-term follow up, five patients remained well controlled with calcitriol pulse therapy, while two patients needed ethanol injections to control hyperparathyroidism. Although we could not completely rule out a toxic effect of the vehicle, direct injection of calcitriol into parathyroid glands may be another treatment option for chronic dialysis patients. Our data further support the important role of resistance of parathyroid cells to calcitriol in the pathogenesis of parathyroid hyper function in uraemic patients.