Changes of cancer diagnosis disclosure to children in Japan in the last 20 years

International Journal of Clinical Oncology - The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change...     

Platinum levels in various tissues of a patient who died 181 days after cisplatin overdosing determined by electrospray ionization mass spectrometry

Platinum (Pt) levels were determined in various tissues and body fluids obtained from a patient who died 181 days after cisplatin overdosing. The symptoms of cisplatin overdose, however, might have almost disappeared by day 40, and the patient’s death was ascribed to the recurrence of malignant lymphoma. Determination of Pt derived from cisplatin was performed by electrospray ionization mass spectrometry (ESI-MS) using silver (Ag) as internal standard. Pt and Ag complexed with diethyldithiocarbamate (DDC) in wetashed blood, and tissue solutions were extracted into isoamyl alcohol, and then acidified with oxalic acid. By injecting an aliquot of the isoamyl alcohol layer into a mass spectrometer in the direct flow injection mode, the quantitation was performed using the signals of Pt(DDC)₃ ⁺ and Ag(DDC)₂ ⁺ at m/z 639 and 403, respectively. The Pt levels ranged from 25ng/ml in blood to 2050ng/g wet weight in the liver of the patient, indicating that Pt remained at high levels in tissues, even after a period as long as 181 days after cisplatin overdosing.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

Effects of dietary restriction on age-related immune dysfunction in the senescence accelerated mouse (SAM)

The effects of age and dietary restriction on immune response were investigated using an animal model of accelerated senescence (senescence accelerated mouse, SAM). The experimental groups consisted of control (ad libitum fed) and restricted groups (fed 60% of energy intake of the controls). Spleen weight and total number of splenic cells were significantly lower in the food-restricted group at 8 mo of age. Percentages of T (Thy-1.1+) and B (surface Ig+) cells in the splenic cells were not significantly different between the two groups. The number of direct hemolytic plaque-forming cells per 10(6) spleen cells 4 d following immunization with sheep red blood cells and dinitrophenyl-Ficoll was significantly greater in the 8-mo-old mice in the food-restricted group than in the control group. In the latter group, antibody responses Progressively decreased with age. Mitogen responses to concanavalin A and lipopolysaccharide were maintained in the food-restricted group but were depressed in the control group at 8 mo. In addition, though autoantibody to single-stranded DNA increased in the control group with advancing age, there was a steady decrease in the food-restricted group until 8 mo. Serum immunoglobulin (IgA and IgM) concentrations were significantly lower in the food-restricted group than in controls at 8 mo of age. Therefore, our results suggest that when senescence accelerated mice are subjected to food restriction, there may be a modulatory effect on the immune dysfunction associated with advancing age.     

Different antigenic nature in apparently healthy women with high serum CA 125 levels compared with typical patients with ovarian cancer.

BACKGROUND. CA 125 is a representative ovarian cancer-associated antigen defined by monoclonal antibody OC125. Recently, monoclonal antibodies were produced (designated 130-22 and 145-9) that were reactive with CA 125 but bound to a separate epitope named CA 130. There was a close correlation between serum CA 125 and CA 130 values in most instances. However, among more than 8000 serum samples, 5 apparently normal women had high serum CA 125 values, despite having normal CA 130 values. In this study, the antigenic nature of these five women was investigated. METHODS. Using gel chromatography, the molecular masses of CA 125 and CA 130 were estimated that were found in the five women with false-positive CA 125 values. The sera were examined using double-determinant assays combining iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OCI25-coated or 145-9-coated beads. RESULTS. The molecular masses of both CA 125 and CA 130 were estimated as greater than 1000 kilodaltons (KD); the CA 130 mass from one of the five women with an abnormal CA 125 level was approximately 200 KD using gel chromatography. Using the double-determinant assays that combined iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OC125-coated or 145-9-coated beads, high radioactivity was found only in the homologous assay using iodine-125-labeled OC125 with OC125-coated beads. These results suggest that the antigenic nature of CA 125 found in apparently healthy women differs from that found in patients with ovarian cancer and that CA 130 epitopes are not present. CONCLUSIONS. Measurement of serum CA 130 concentrations may be useful for excluding women with falsely elevated CA 125 values.     

MR appearance of parasymphyseal insufficiency fractures of the os pubis

 Objective. To clarify the MRI features of parasymphyseal insufficiency fractures of the os pubis. Design and patients. MRI was performed in four postmenopausal women with parasymphyseal insufficiency fractures. The diagnosis was confirmed with plain films in every patient. T1-weighted and T2-weighted images were obtained in four patients using a 1.5-T unit. Postcontrast T1-weighted imaging was also done in three patients. Results and conclusions. MRI of pubic parasymphyseal insufficiency fracture characteristically demonstrates a hyperintense mass lesion with a hypointense rim on T2-weighted imaging, showing peripheral and septal enhancement after contrast administration. It is important to have this entity in mind in patients with osteoporosis, especially in patients with a history of pelvic irradiation for malignant disease, so as not to misinterpret it as a chondroid tumor or bone metastasis.     

Tumor Response to Neoadjuvant Chemotherapy Correlates with the Expression of P-Glycoprotein and PCNA but Not GST-π in the Tumor Cells of Cervical Carcinoma

Objective.To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas.Methods.We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathioneS-transferase π (GST-π), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied.Results.Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P< 0.005) and low PCNA labeling (P< 0.05), but not GST-π expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-π nor PCNA was correlated with the patient survival.Conclusion.Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.     

Coronary vasodilator versus cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in the dog heart

We compared the coronary vasodilator and cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. The drug was administered intraarterially. In SA node preparations MCI-176 reduced sinus rate and produced atrial standstill in large doses. In AV node preparations MCI-176 prolonged AV conduction time and produced second- or third-degree AV block in large doses only when administered into the artery supplying the AV node, but failed to affect AV conduction when administered into the artery supplying the His-Purkinje-ventricular system. In paced papillary muscle preparations MCI-176 reduced the force of contraction. In spontaneously beating papillary muscles MCI-176 failed to change the beating rate. MCI-176 increased blood flow in all preparations. The dose that doubled blood flow was slightly larger than the dose that produced a 15% increase in AV conduction time, but about one-third the dose that produced a 15% decrease in sinus rate. The dose estimated to reduce the force of contraction by half was more than approximately 10 times the dose that doubled blood flow. The results indicate that MCI-176 can be classified as a nonvasoselective calcium antagonist but that it differs from others.     

A case of melorheostosis with a 14-year follow-up

Melorheostosis is a benign sclerosing dysplasia with a very unusual and characteristic roentgenographic appearance. We reported a patient with melorheostosis in the left lower extremity followed up for 14 years. Although the extraosseous lesions only slightly enlarged, the bone scintigraphy showed the activity of the metabolism to be still high.     

Statistical and integrative approach for constructing biological network maps

A goal of systems biology is to build a concrete biochemical network map, which provides an important instruction to trace the pathways of interest or to understand the mechanism of a biological system. In the postgenomic era, not only the concrete biochemical maps, but also postgenomic maps (mRNA coexpression and protein-protein interaction networks) have been extensively produced. In the biochemical map, the individual reactions are reliable, but the number of the reactions is limited, because molecular biology requires extensive experiments to verify them. By contrast, postgenomic data provide much information regarding interactions, but are coarse-grained. To expand the biochemical network, an intuitional approach, which superposes postgenomic data on the map one by one, has been carried out, but it is not effective when a large amount of the coarse-grained data is handled. In order to effectively integrate such postgenomic interactions into a biochemical map, a statistical approach would be suitable rather than intuition. In this article, we proposed a novel statistical approach that integrates postgenomic interaction networks into the biochemical network, predicting novel pathways. A statistical correlation for such different types of networks identifies functional modules; subsequently the superposition of the different networks on the functional modules predicts inter-modular relations, which are the key pathways to construct a large-scale biochemical network.