Role of p53 mutations in endocrine tumorigenesis: mutation detection by polymerase chain reaction-single strand conformation polymorphism.

To elucidate the molecular basis for endocrine tumorigenesis, p53 mutations in human endocrine tumors were analyzed by using polymerase chain reaction-single strand conformation polymorphism. Exons 5 through 10 of the p53 gene were studied in genomic DNAs from 134 primary endocrine tumors and 6 human endocrine cancer-derived cell lines. Mutations were detected and identified in 4 endocrine tumors, including one parathyroid adenoma and three thyroid carcinoma cell lines. The sites of these mutations were in exons 5 (codon 151 and 152) and 7 (codon 248 and 255). In all of three tumor cell lines, but not in a parathyroid adenoma, the normal allele encoding the p53 gene was lost. However, p53 mutations were not found in any other endocrine tumors or cell lines. Based upon these results, we concluded that the p53 gene may play a role in the tumorigenesis of a limited number of parathyroid adenoma and thyroid cancers, and that the p53 mutation with an allelic loss of the p53 gene is an important factor in malignant tumorigenesis of the thyroid gland.     

Lectin histochemistry in mucinous and serous ovarian neoplasms.

The lectin-binding properties of 44 cases of serous and mucinous ovarian cystadenoma, tumor of low malignant potential (LMP), and invasive carcinoma were examined histochemically. Wheat germ agglutinin (WGA), concanavalin A (con A), Ulex europaeus agglutinin I (UEA-I), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA-I), soybean agglutinin (SBA), and Robina pseudoaccacia (RPA) were employed. All the lectins examined were bound to neoplastic epithelial cells of benign and malignant tumors, but none bound exclusively to ovarian tumor cells. Different lectin-binding patterns between serous and mucinous neoplasms were observed, with the exception of RPA. UEA-I, con A, RPA, and PNA in serous neoplasms and UEA-I, RPA, and WGA in mucinous neoplasms demonstrated lectin-binding properties of LMP tumors intermediate between those of cystadenoma and invasive carcinoma. These findings indicate that serous and mucinous ovarian neoplasms contain different glycoconjugates, that malignant transformation of the neoplasms is associated with alteration of these glycoconjugates, and especially that LMP tumors have a different composition of cellular glycoconjugates from that of invasive ovarian carcinoma.     

Comparative in vitro and in vivo activity of rifabutin and rifampicin against Mycobacterium avium complex

In vitro antimicrobial activity of rifabutin and rifampicin against various mycobacteria, including the Mycobacterium avium complex, was evaluated by the agar dilution method, using 7H10 agar medium. The activity of rifabutin based on MIC50 and MIC90 was higher than that of rifampicin, against all the acid-fast organisms tested. Microbicidal activity of rifabutin against the M. avium complex phagocytosed in mouse peritoneal or alveolar macrophages was greater than that of rifampicin. Both rifabutin and rifampicin had therapeutic effects against murine infections induced by M. avium complex. Rifabutin was somewhat more effective than rifampicin in mice.     

Minimal osteonecrosis as a segmental infarct within the femoral head

Minimal osteonecrosis (MON) is a small and eccentrically localized lesion of osteonecrosis (ON) of the femoral head. This form of ON shows clinically benign features, but may be indicative of the pathomechanism of ON. Of 180 patients (275 hips) with ON, 15 patients (19 hips) were found to have MON. Based on the geography of the femoral head, the lesions were grouped into four types: anterior (seven hips), superior (six hips), medial (five hips), and lateral (one hip). When the location of the lesion was compared with the normal vascular anatomy, a close correlation between the location and the segmental blood supply in the femoral head became evident. Histologic findings showed localized infarction of the trabeculae and bone marrow, but no evidence suggesting repeated episodes of infarction, which is an essential feature of typical ON. From these findings, MON may be a segmental infarct within the femoral head. Interruption of the blood flow may possibly occur not in the main trunk but in the terminal branch of the lateral epiphyseal or superior metaphyseal artery; such as ischemic event is probably a single brief attack, leading to this form of infarction in contrast to typical ON developing with prolonged or recurrent obstructions.     

Universal applications of sentinel node technology

The sentinel node (SN) concept was originally proposed by several pioneers in the middle of the last century. After Donald Morton and his colleagues demonstrated the clinical significance of the SN concept in melanoma, it attracted vast attention in surgical oncology. At recent international conferences, a number of new approaches in this field for various solid tumors have been reported. Now, there are several possible applications with different technological aspects, such as individualized surgical management of solid tumors, multidisciplinary treatments, and novel therapeutic approaches. This article provides an overview of the future potential of SN technology.     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

Preoperative chemotherapy increases cytokine production after lung cancer surgery.

OBJECTIVE: Many phase II trials have shown that preoperative chemotherapy for lung cancer is feasible but associated with postoperative morbidity and mortality. However, little is known about the effect of preoperative chemotherapy on surgical stress and postoperative complications associated with surgical intervention. We evaluated the effect of preoperative chemotherapy on perioperative inflammatory cytokine production as a surgical stress marker. METHODS: The study group comprised 38 patients undergoing anatomical lung resection and mediastinal nodal dissection for clinical stage IB/II non-small cell lung cancer during the period October 2001-December 2003. Nineteen patients received a single cycle of cisplatin (80 mg/m(2)) and docetaxel (60 mg/m(2)) chemotherapy prior to surgery (neoadjuvant group), and 19 patients underwent surgery without any previous chemotherapy (control group). White blood cell and neutrophil counts and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (GCSF) were determined before surgery and on postoperative days 1 and 3. Postoperative complications were reviewed. Differences were assessed by repeated analysis of variance. RESULTS: Serum concentrations of IL-6 and GCSF rose significantly on postoperative days 1 and 3 in the neoadjuvant group in comparison to concentrations in the control group, but white blood cell count, neutrophil count, and CRP did not differ between the groups. No major complication occurred in either group. CONCLUSIONS: A single cycle of cisplatin and docetaxel chemotherapy followed by surgery can exacerbate overproduction of inflammatory cytokines during the perioperative period in lung cancer patients.