Preoperative evaluation of the deep cerebral veins using 3-tesla magnetic resonance imaging.

BACKGROUND: Surgical treatment of deep-seated tumors such as supratentorial intraventricular and thalamic-pineal-tectal region tumors carries a risk of postoperative deficits due to possible damage to deep cerebral veins including the internal cerebral vein. It is often difficult to identify whether the vessel encountered during surgery needs to be preserved or not through the small operative field. Therefore, preoperative evaluation of deep venous structures is important. We evaluated the usefulness of 3-Tesla magnetic resonance imaging (3 T MRI) for this purpose. METHODS: First, the ability to detect deep venous structures was compared with both 3-dimensional computed tomographical angiography (3D-CTA) and 3 T MRI in patients without any damage to deep venous structures. Images of 7 consecutive patients suffering from insulo-opercular gliomas who underwent both imaging modes for the identification of lateral striate arteries were reconstructed for evaluation of the deep cerebral veins. Subsequently, surgery for tumors at the supratentorial intraventricular and thalamic-pineal-tectal regions was prospectively performed with preoperative evaluation of deep venous system only using 3 T MRI. RESULTS: Information on the deep venous systems acquired by 3 T MRI was as useful as that acquired by 3D-CTA. Until today, we have treated 8 cases of supratentorial intraventricular and thalamic-pineal-tectal region tumors with preoperative evaluation of the deep venous system using 3 T MRI without any morbidity. CONCLUSION: Information on the deep venous system obtained with 3 T MRI aids the surgery of supratentorial intraventricular and thalamic-pineal-tectal region tumors. As the required sequences of 3 T MRI are same as those necessary for the neuronavigation system, and 3 T MRI can be achieved without the use of iodine-based contrast agents, 3 T MRI can be an alternative for preoperative evaluation of the deep venous systems.

A case of idiopathic hypereosinophilic syndrome with leptomeningeal dissemination and intraventricular mass lesion: an autopsy report.

A 43-year-old female presented with idiopathic hypereosinophilic syndrome (HES) manifesting as an intraventricular mass lesion and leptomeningeal and cerebral parenchymal infiltration by eosinophils, lymphocytes and macrophages. She had no history of either malignancy or allergic disorder. She complained of hearing disturbance caused by eosinophilic otitis media. Eosinophilia was detected in the peripheral blood. Hearing disturbance and eosinophilia improved with corticosteroid treatment. Six months later, she was admitted with disturbances of consciousness. Magnetic resonance imaging revealed a mass lesion in the right lateral ventricle and leptomeningeal involvement around the brain stem. Her symptoms deteriorated rapidly, and she died of brain stem malfunction. Autopsy demonstrated significant infiltration by eosinophils and lymphocytes into the mass lesion in the ventricle, subarachnoid space, perivascular space and parenchyma of the medulla oblongata. Histological examination of the bone marrow and other organs did not detect any evidence of parasites, malignancies, or systemic disorders in any organ. The final diagnosis was idiopathic HES. The present case shows that leptomeningeal dissemination and infiltration by eosinophils into the cerebral ventricles and brain stem should be considered in the course of idiopathic HES.

Ossification of the thoracic ligamentum flavum in an achondroplastic patient: a case report.

We report a case of spinal stenosis with ossification of the thoracic ligamentum flavum in a 53-year-old man with achondroplasia. Neurological signs indicated flaccid paralysis below L1, and the patient was unable to walk. Ossification of the ligamentum flavum was observed at T4/5 and T9 to T12, compressing the thecal sac. Laminectomy of T9 to L1 was performed. At one-year follow-up, the patient was able to walk with one elbow crutch.

Giant cell reparative granuloma of the proximal tibia: a case report.

Giant cell reparative granulomas (GCRGs) are non-neoplastic inflammatory lesions, usually of the jaw or gingiva or small bones of the hands and feet. We report one such case in the right proximal tibia of a 45-year-old man. Radiological studies showed a lytic lesion with marginal sclerosis in the epiphysis and metaphysis. After open biopsy, a preliminary diagnosis of a benign giant cell tumour was made. One month after admission, the lesion was curetted and filled with cancellous bone and hydroxyapatite. Based on the histology of the curetted lesion, the diagnosis was changed to a GCRG. The patient had an uneventful postoperative course, with no evidence of local recurrence and metastasis. He died from gastric cancer 2 years later.

Acral myxoinflammatory fibroblastic sarcoma of the foot.

We report a rare case of acral myxoinflammatory fibroblastic sarcoma (AMFS) in a 68-year-old woman. Tumor excision of a mass between the 1st and 2nd toe of the left foot was performed after a diagnosis of ganglion in February 2003. Examination of the surgical specimen confirmed AMFS. No recurrence or metastasis occurred during the follow-up period of 4 years. Clinical characteristics such as recurrence rate, metastasis rate and period of metastasis are unclear for AMFS. Long-term clinical follow-up is thus required.

Genetic analysis of high-metastatic clone of RCT sarcoma in mice, and its growth regression in vivo in response to angiogenesis inhibitor TNP-470.

Genetic analysis of a high-metastatic clone of RCT sarcoma (HM-RCT) was the aim of the study. HM-RCT was developed by the lung passage as well as limiting dilution method from the original RCT sarcoma, in which a tumor was spontaneously developed in a C3H/He mouse. HM-RCT expressed enhanced POU domain (class 2, associating factor 1), adenylate cyclase 7, procollagen type III (alpha), A kinase anchor protein 4 and Ehm (expressed on high-metastatic cells) and 11 expressed sequence tags (ESTs). compared with the original clone of RCT. Eighteen specific genes and 14 ESTs were underexpressed in HM-RCT. We investigated the effects of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of this HM-RCT in vivo. In an experimental group, mice received TNP-470 (30 mg/kg) intraperitoneally every other day. After 5 weeks, the growth of the TNP-470-treated tumor was significantly suppressed in vivo, but did not affect the metastasis. The proportion of positive PCNA-stained cells and cellular telomerase activity was significantly low in response to TNP-470.

Comparison of biological effects of modulated electro-hyperthermia and conventional heat treatment in human lymphoma U937 cells.

Loco-regional hyperthermia treatment has long history in oncology. Modulated electro-hyperthermia (mEHT, trade name: oncothermia) is an emerging curative treatment method in this field due to its highly selective actions. The impedance-matched, capacitive-coupled modulated radiofrequency (RF) current is selectively focused in the malignant cell membrane of the cancer cells. Our objective is studying the cell-death process and comparing the cellular effects of conventional water-bath hyperthermia treatment to mEHT. The U937 human histiocytic lymphoma cell line was used for the experiments. In the case of conventional hyperthermia treatment, cells were immersed in a thermoregulated water bath, whereas in the case of mEHT, the cells were treated using a special RF generator (LabEHY, Oncotherm) and an applicator. The heating dynamics, the maximum temperature reached (42 °C) and the treatment duration (30 min) were exactly the same in both cases. Cell samples were analysed using different flow cytometric methods as well as microarray gene expression assay and western blot analysis was also used to reveal the molecular basis of the induced effects. Definite difference was observed in the biological response to different heat treatments. At 42 °C, only mEHT induced significant apoptotic cell death. The GeneChip analysis revealed a whole cluster of genes, which are highly up-regulated in case of only RF heating, but not in conventional heating. The Fas, c-Jun N-terminal kinases (JNK) and ERK signalling pathway was the dominant factor to induce apoptotic cell death in mEHT, whereas the cell-protective mechanisms dominated in case of conventional heating. This study has clearly shown that conventional hyperthermia and RF mEHT can result in different biological responses at the same temperature. The reason for the difference is the distinct, non-homogenous energy distribution on the cell membrane, which activates cell death-related signalling pathways in mEHT treatment but not in conventional heat treatment.

Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene.

High-frequent microsatellite instability (MSI-H) was detected in two of the 80 gliomas examined, whlie the other 78 gliomas showed microsatellite stable (MSS) phenotype. Both of the two MSI-H tumors were glioblastomas which developed in teenage patients. One of the patient was diagnosed as having Turcot's syndrome and had a germline mutation in the hMLH1 gene. Loss of expression due to promoter methylation was selectively observed in the wild type allele of the hMLH1 gene in the tumor of this patient. The other patient had neither a family history nor a past personal history of malignancy. Although no mutation in the mismatch repair genes was detected in the tumor of this patient, the level of expression of the hMLH1 gene was markedly decreased and the promoter sequence of the gene was highly methylated. In the tumor of this patient, the PTEN1 gene, one of the genes carrying microsatellite sequences in their coding regions, was altered by a slippage mutation within five adenine repeat sequences. These findings indicate that the genetic or epigenentic inactivation of the hMLH1 gene is involved in a subset of early-onset gliomas and the PTEN1 gene could be a downstream target for mutation as observed in glioblastoma without MSI.

Purification and partial characterization of a protein proteinanse inhibitor isolated from eggplant exocarp.

A protein proteinase inhibitor was isolated and purified from eggplant exocarp by heat treatment, ammomium sulfate fractionation, column chromatography on DEAE-cellulose, and gel filtration on Sephadex G-25 and G-50. The final purified preparation of the inhibitor was found homogeneous by electrophoretic analysis. The inhibitor showed strong and stoichiometric inhibition on trypsin whereas it showed weak inhibition on alpha-chymotrypsin. It displayed no inhibiting characteristics on pepsin. The molecular weight of the inhibitor was estimated to be approximately 6000. This finding, with the trypsin inhibition data, suggested that the inhibitor combined trypsin in the molar ratio of 1:1. The amino acid analysis indicated that the inhibitor is rich in half-cystine, glycine and aspartic acid, and contains no tryptophan, histidine, methionine or valine.

Curettage and radiotherapy of giant cell tumour of the sacrum: a case report with a 10-year follow-up.

A case report of a 53-year-old woman with giant cell tumour of the sacrum is presented. Initial curettage was performed through a posterior approach and the patient was relieved of pain and discharged. However, 6 months later the patient was readmitted with a tumour that had progressed towards the L5 vertebra. A further curettage followed by adjuvant radiotherapy resulted in successful reduction of the tumour. Ten years after the operation, there was no recurrence or metastasis.

Post-immigration Changes in Social Capital and Substance Use Among Recent Latino Immigrants in South Florida: Differences by Documentation Status.

Changing social capital among recent Latino immigrants (RLIs) influences substance use post-immigration. This was a longitudinal study of 476 South/Central American RLIs examining social capital and substance use changes pre to post-immigration. Self-reported measures of social capital and substance use were compared between surveys administered within 1 year of immigration and 2 years post-immigration. Post-immigration, social capital, hazardous drinking and illicit drug use decreased. Women were less likely to engage in hazardous drinking [adjusted odds ratio (AOR) .32, p < .001], and less likely to use illicit drugs (AOR .67, p = .01). Documented individuals with higher levels of 'business' social capital had increased odds of illicit drug use (AOR 2.20, p < .05). Undocumented individuals with higher levels of 'friend and others' social capital had decreased risk for hazardous drinking and illicit drug use (AOR .55, p < .01; AOR .56, p < .05). Documentation status moderated the relationship between social capital and substance use. RLIs can be targeted for primary prevention of substance abuse.

Developmental changes in pharmacokinetics and pharmacodynamics of warfarin enantiomers in Japanese children.

OBJECTIVE: To clarify developmental changes in the pharmacokinetics and dynamics of warfarin enantiomers to establish rational pediatric dosage. METHODS: Plasma concentrations of unbound warfarin enantiomers, vitamin K1 and vitamin K-dependent proteins (that is, prothrombin fragments 1+2, protein C, and the protein-induced by vitamin K absence) and international normalized ratio were measured in 38 prepubertal (1 to 11 years), 15 pubertal (12 to 18 years), and 81 adult (37 to 76 years) patients given long-term warfarin therapy. Unbound oral clearance values for warfarin enantiomers and its body weight-, body surface area-, and liver weight-normalized values, as well as the pharmacodynamic parameters, were compared among the groups. RESULTS: The prepubertal, pubertal, and adult patients exhibited comparable mean plasma concentrations of unbound warfarin enantiomers for pharmacologically more active (S)-warfarin. Although the unbound oral clearance of (S)-warfarin for the prepubertal patients was significantly (P < .01) less than that for the adult group (346 versus 637 mL/min), the body weight-normalized unbound oral clearance for the prepubertal patients was significantly (P < .01) greater than that for the adults and showed a negative correlation (P < .05) with age. In contrast, no differences were observed in the liver weight-normalized unbound oral clearance for (S)-warfarin between the prepubertal and adult groups. The prepubertal patients showed significantly (P < .01 or .05) lower plasma concentrations of protein C and prothrombin fragments 1+2 and greater international normalized ratio and international normalized ratio/dose than the adults. In contrast, the pubertal patients showed largely similar pharmacokinetic and pharmacodynamic properties to adults. CONCLUSION: Liver weight may be a better parameter than body weight for estimating the warfarin doses for prepubertal patients on the basis of the corresponding adult values. Augmented responses to warfarin in children should also be taken into account for estimating warfarin doses for children.

Spontaneous reduction in Epstein-Barr virus (EBV) DNA copy number in EBV-infected epithelial cell lines.

We found that spontaneous and 12-0-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus (EBV) reactivation occurred in short-term (ST)-cultured EBV-infected epithelial cell lines GT38 and GT39 after their establishment; however, it diminished in the long-term (LT)-cultured cells passaged for more than 2 years from ST-cultured cells. We hypothesized that the EBV reactivation may be related to the EBV DNA copy number in the cells. A higher level of EBV DNA content was detected in ST-cultured cells than in LT-cultured cells by Southern hybridization using an EBV DNA XhoI probe. Fluorescence in situ hybridization using EBV DNA BamHI W fragments showed that ST-cultured cells contained a higher EBV DNA copy number than that of LT-cultured cells. EBV DNA-negative cells were detected in small proportions in LT-cultured cells, but were undetected in ST-cultured cells. These results demonstrate that EBV genomes are not maintained stably in the cell lines, and some of them are lost in continuous passages of the cells. We discuss the mechanisms of reduction of EBV reactivation and EBV DNA in the cell lines.

Association between chromosome 11q13 amplification and prognosis of patients with oesophageal carcinomas.

Ninety pairs of normal and tumour tissue DNAs were isolated from paraffin-embedded blocks of advanced oesophageal carcinoma cases and examined for gene amplification at chromosome 11q13 by dot-blot hybridisation using the int-2 gene as a probe. 22 of 90 carcinomas (24%) showed more than two times amplification. Although no significant correlation was observed between gene amplification and histological type or metastasis to lymph node, a tendency for deeper invasion to be associated with more frequent amplification was observed. In relation to prognosis, patients with amplification had a lower survival rate than those without amplification. This tendency was evident both in the group with well differentiated type carcinoma and in the group which had no metastasis to lymph node. Thus, gene amplification of the int-2 locus may be a useful prognostic factor.

Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma.

Adamantinoma of long bones is a rare neoplasm predominantly involving the tibia. Cytogenetic studies of adamantinoma are few. Cytogenetic or molecular cytogenetic analysis of four adamantinomas, and a review of eleven cases in the literature reveals extra copies of chromosomes 7, 8, 12, 19, and 21 as recurrent in this neoplasm. Adamantinoma may be confused with a variety of primary and metastatic epithelial and mesenchymal neoplasms. Observation of these aneuploidies may be useful in establishing the diagnosis of adamantinoma.

Genomic structure of human alpha-pix, and variable deletions in a poly (T) tract in gastric cancer tissue.

PAK-interacting exchange factor (PIX) has been reported to mediate the recruitment of PAK into focal adhesions and activate Rac, thus creating a feedback loop that stimulate PAK and other targets. This pathway is thought to be related to cellular changes, such as transformation and migration, that are often encountered in cancer cells. Here, we report the genomic structure of alpha-PIX, one of the PAK- interacting exchange factors, including the identification of the promoter region, which consisted 772 amino acids in 22 exons, spanning about 100 kb on genome of X chromosome. All splice sites conformed to the GT-AT rule. To investigate the role of alpha-PIX in carcinogenesis, we screened 60 cases of gastric cancer for mutations and polymorphisms using an intron-primer that covered all the exons, but no mutations or polymorphisms were found in the coding region. However an 18 bp repeat of thymidine tract was present in 50 bp downstream from exon 12 and the deletion of variable numbers of mononucleotide repeats was observed in seven out of the 60 gastric cancer tissue specimens that were examined. These seven cases all exhibited a mutator phenotype, suggesting that the deletions are passenger mutations. Thus our results revealed that alpha-PIX probably does not play any primary role in human gastric carcinogenesis.

Notable minimum value of relative risk recognized by Japanese epidemiologists and rule of proof in civil trial: questionnaire survey.

Members of The Japanese Society of Cancer Epidemiology were questioned about relative risk in cancer epidemiology. The notable minimum value of relative risk recognized by the epidemiologists distributed from 1.1 to 5.0, and the mean and the standard deviation of the notable minimum value were 1.92 and 0.760. In civil litigation of United States a plaintiff must prove one's case by a "preponderance of evidence," which means that a causal relationship between risk factors and a health disturbance to a plaintiff is proved when relative risk is 2.0 or more. The mean value 1.92 of the notable minimum value of relative risk nearly corresponded to the relative risk 2.0, which indicates that opinion of Japanese epidemiologists did not disagree with the rule of the proof in civil litigation of United States. It is mentioned that the standard of the proof should be "high probability" based on "a high level of conviction in the judge's own mind" in Japanese civil trials, and that the "high probability" means that relative risk is 5.0 or more if we dare to quantify the vagueness. This value corresponded to the maximum value of the notable minimum relative risk in the questionnaire to the Japanese epidemiologists. In civil litigation of Japan, the standard of the proof based on epidemiological results may be more conservative than the opinion of Japanese epidemiologists.

Calcitonin receptors on neoplastic mononuclear cells cultured from a human giant-cell tumor of the sacrum.

Saturable, specific, high-affinity calcitonin receptors were demonstrated in cultured neoplastic mononuclear spindle cells from a giant-cell tumor of the sacrum of a 38-year-old woman. The receptor was analyzed by autoradiography and 125I-calcitonin binding assay. Binding reversibility of 125I-calcitonin to the cells was not complete and the structural specificity was indicated by the inability of unrelated hormones to compete with calcitonin. The 24,000 receptors/cell and dissociation constant (Kd) of 8.0 x 10(-10) M, calculated from linear Scatchard plots, suggested the existence of a single class of calcitonin binding sites in the neoplastic mononuclear cells. Flow-cytometric analysis in the primary culture showed that mononuclear cells consisted of mononuclear round cells of monocyte/macrophage lineage, which express more calcitonin receptors than neoplastic mononuclear spindle cells. Administration of calcitonin caused morphological and physiological alterations, resulting in involutional or irregular cytoplasmic shapes and inhibition of DNA synthesis in neoplastic mononuclear cells accompanied by the escape phenomenon. Cells preincubated with calcitonin showed a decrease in 125I-calcitonin binding activity, which could account for the escape phenomenon. The decrease in 125I-calcitonin binding was rapid, but the recovery was not observed for 24 h after elimination of calcitonin. This decrease may be caused by the disappearance of residual receptors or by a decrease in calcitonin affinity. The calcitonin-induced morphological changes and the inhibition of DNA synthesis of cells were revealed to be mediated by calcitonin receptors.

Differentiation of Dunn osteosarcoma cells in response to dibutyryl cyclic 3',5'-adenosine monophosphate.

We investigated the effects of dibutyryl cyclic adenosine 3',5'-monophosphate (Bt2cAMP) on the differentiation of Dunn osteosarcoma cells. Flow-cytometric analysis and DNA synthesis assay showed that Bt2cAMP decreased the cell population in the S phase in a time- and dose-dependent manner. Also, the cells showed distinct morphological and functional alterations; the cell morphology changed to a fibroblast-like appearance with long and thin protoplasmic processes, the knobs or blebs on both the cell membrane and nuclear membrane disappeared and the intracellular alkaline phosphatase activity increased. Moreover, Bt2cAMP-treated cells secreted a large quantity of fibronectin, which was deposited on the extended cell surface in the culture medium. Thus, Dunn osteosarcoma cells are differentiated morphologically and functionally by Bt2cAMP, and might be transformed to benign precursor cells.

Synthesis of elastin. A rapid formation of lysine-derived crosslinks by chick embryo aorta.

Aortas of 13-day-old chick embryo were labeled for 0.5 hr with [14C]lysine and subjected to a serial extraction after chase for 1-24 hr with [12C]lysine. Substantial radioactivity was found in insoluble elastin after 3 hr chase. The effect of beta-amino-propionitrile on labeling with [14C]lysine was also examined. Each fraction was hydrolyzed and applied to a short column on an amino acid analyzer. Radioactivity was found in desmosine and isodesmosine of insoluble elastin as early as 1 hr after the beginning of chase. The radioactivity increased rapidly at 2 hr and very slowly thereafter. A large count, which was separated into five peaks on a long column, was observed in other lysine derivatives at 2 hr and increased steadily up to 24 hr, while the lysine count decreased from 1 : 0.5 to 1 : 6 against lysine derivatives and from 1 : 0.04 to 1 : 0.9 against quarter-desmosine after 24 hr. The oxidation of lysine residues incorporated during the 0.5 hr pulse was almost completed during the first 1 hr of chase, and these oxidized residues were incorporated into crosslinks during the following 1 hr. It is suggested that poorly crosslinked elastin accumulated in the soluble fractions. The presence of crosslinking derived from lysine residues was also indicated in the microfibril fraction.