Gene testing of hereditary cancer on comprehensive gene medical examination support system

It has been estimated that genetic factors or a combination of genetic and environmental factors play a role in the development of 10-15% of all cancers. A genetic cause of hereditary cancer has been identified in more than 40 diseases till now. For preventing this cancer, gene testing is essential because it has no definite clinical marker as in hereditary non-polyposis colorectal cancer: HNPCC. Much more experience must be accumulated in this testing at the clinical base in order to increase specificity and sensitivity while safeguarding ethical, legal and social issues (ELSI). Recently, the Personal Information Protection Law was enforced. Gene inspection involving hereditary cancer should be carried out under a comprehensive gene medical examination organization. It is important for the family doctor, medical specialist, and gene inspection person in charge to cooperate closely with one another, and this will be a subject of future study.     

Reduced radiosensitivity and increased CD40 expression in cyclophosphamide-resistant subclones established from human cervical squamous cell carcinoma cells

To investigate the interaction between anticancer drug resistance and radioresistance in cervical cancer cells, 3 single cell-derived cyclophosphamide-resistant subclones were established from the drug- and radiosensitive human cervical squamous cell carcinoma cell line ME180 by chronic exposure cultures with 4-hydroxy-cyclophosphamide followed by limiting dilution. The established cyclophosphamide-resistant subclones were also radio- and multidrug-resistant to 7 other anticancer drugs. Flow cytometric analysis revealed significantly increased levels of CD40 expression on the 3 resistant subclones, whereas no CD40 expression was found on the parent ME180 cells. However, there were no changes in the expression levels of CD29, CD49a-CD49f or CD59 between the parent cells and resistant subclones. A recombinant human soluble CD40 ligand had no effect on the proliferation of the resistant subclones. Irradiation had no effect on the 4-hydroxy-cyclophosphamide sensitivity of the parent cells. These results indicate that the established cyclophosphamide-resistant subclones have impaired cell death signals, which are common to both drug- and radiation-induced apoptosis, and cyclophosphamide may not be an adequate drug for use in concurrent chemoradiotherapy. Furthermore, CD40 activation signals may be associated with the multidrug- and radioresistance in these cyclophosphamide-resistant subclones.     

Pachymeningoencephalitis: case report

A 59-year-old man presented with generalized convulsion. MR imaging demonstrated a homogeneously enhanced dural lesion infiltrating the parenchyma in the right parietal region. He had no history of sinusitis and the lesion a resembled malignant tumors, so surgical treatment was performed. The histopathological studies showed pachymeningitis extending to the cerebral parenchyma, so the diagnosis of pachymeningoencephalitis was made. After the operation, the patient had no neurological deficits and anticonvulsant therapy was continued. We report the third case of idiopathic local pachymenigoencephalitis that we could range extensively in the world. The clinical features and pathogenesis are discussed.     

Emergency drainage for urosepsis associated with upper urinary tract calculi

PURPOSE: We examined the characteristics of patients with urosepsis associated with upper urinary tract calculi requiring emergency drainage. MATERIALS AND METHODS: From January 1994 to December 2003, 424 patients were admitted to our urological department a total of 473 times for treatment of upper urinary tract calculi, of whom 53 required a total of 59 emergency drainage procedures for urosepsis. We summarized the characteristics of these patients and events, and determined risk factors for emergency drainage using logistic regression analysis. RESULTS: In 14 events (24%) intensive management, such as the use of vasopressors and anticoagulants, was performed. Transient thrombocytopenia less than 100,000/mm occurred in 18 events (31%). Hyperbilirubinemia occurred in 8 of 38 events (16%) without prior antibiotic therapy. One patient (2%) died of urosepsis. Patients with calculi who underwent emergency drainage required a longer hospital stay than those without emergency drainage (25.2 vs 14.8 days, p <0.001). Of the variables analyzed poor performance status (Karnofsky performance status 70% or less, OR 2.9, p = 0.003), age 75 years or older (OR 2.1, p = 0.038) and female sex (OR 1.8, p = 0.046) were risk factors on multivariate analysis. CONCLUSIONS: Our findings suggest that the frequency of emergency drainage in elderly patients with poor performance status has increased in recent years, at least in our rural area of Japan. Preventing calculous formation and urinary tract infection in individuals with poor performance status will be of considerable importance in the future.     

GalNAc-GD1a is localized specifically in ventral spinal roots, but not in dorsal spinal roots

We investigated the localization of GalNAc-GD1a biochemically in the human and bovine peripheral nervous system (PNS). The high-performance thin-layer chromatography (HPTLC)-overlay method with rabbit IgG polyclonal antibody against GalNAc-GD1a (anti-GalNAc-GD1a antibody) revealed expression of GalNAc-GD1a in the ventral spinal nerve roots (VRs) but not in the dorsal spinal nerve roots (DRs) of both species. The amount of GalNAc-GD1a in the human and bovine VRs was 2.22 +/- 0.35 microg/g wet tissue and 7.71 +/- 0.49 microg/g wet tissue, respectively. These results suggest that IgG anti-GalNAc-GD1a antibody may be involved in disturbance of peripheral motor nerves and in the pathogenesis of pure motor neuropathy.