Association of BRCA2 polymorphism at codon 784 (Met/Val) with breast cancer risk and prognosis.

PURPOSE: The association of BRCA2 polymorphisms at codon 372 [Asn (N)/His (H)]and codon 784 [Met (M)/Val (V)] with breast cancer risk was evaluated in Japanese women. In addition, the prognostic significance of these polymorphisms was studied in breast cancer patients. EXPERIMENTAL DESIGN: A case-control study was conducted to examine the association of the BRCA2 N/H372 polymorphism and M/V 784 polymorphism with breast cancer risk (cases = 149, controls = 154). The prognostic significance of these polymorphisms was evaluated in 139 patients with primary breast cancer. RESULTS: No significant association was observed between the N/H372 polymorphism and breast cancer risk. In contrast, a significant increase in breast cancer risk (odds ratio, 2.03; 95% confidence interval, 1.07-3.87) was observed in carriers of the variant allele (V784) of the M/V784 polymorphism as compared with noncarriers after adjustment for the classical risk factors, age, family history, parity, body mass index, and so forth. Among breast cancer patients, various clinicopathological parameters including menopausal status, tumor size, lymph node status, histological grade, and estrogen-receptor status were not significantly different between the carriers and noncarriers of the variant allele with regard to both N/H372 and M/V784 polymorphisms. The N/H 372 polymorphism was not significantly associated with patient prognosis. On the other hand, breast cancer patients carrying the variant allele of M/V784 polymorphism showed a significantly (P = 0.014) lower 3-year disease-free survival rate (63%) than noncarriers (92%). Multivariate analysis has revealed that the M/V784 polymorphism is a significant prognostic factor, being independent of the other conventional prognostic factors such as lymph node status and estrogen receptor status. CONCLUSION: These results suggest that the M/V784 polymorphism, but not the N/H372 polymorphism, would be useful in the selection of women at high risk for developing breast cancer and would also serve as a clinically useful prognostic factor in breast cancer patients.     

In Vitro Evaluation of Platelet/Biomaterial Interactions in an Epifluorescent Video Microscopy Combined with a Parallel Plate Flow Cell

Abstract: Suitable evaluation systems are critical for ranking various biomaterials in order to develop a method to design and synthesize nonthrombogenic biomaterials. We have recently developed an in vitro test system to evaluate platelet/biomaterial interactions in whole blood. The system consists of a parallel plate flow cell and epifluorescent video microscopy (EVM). A glass coverslip coated with a polymer was incorporated into the flow cell, and blood was perfused using a syringe pump via a polymer–coated PVC tubing connected to the flow cell. Whole human blood was anticoagulated with heparin (2 U/ml), and the platelets were labeled with the fluorescent dye mepacrine (5 μM). This system permitted real–time and dynamic observations of platelet/biomaterial interactions in whole blood under a defined flow condition. In order to evaluate the feasibility of this system, two different segmented polyether–polyurethanes (SPEUs), PU–PTMG(650) and PU–PTMG(2000), were chosen as test polymers. Surface characteristics verified with electron spectroscopy for chemical analysis (ESCA) and contact angle measurements showed similar results in both SPEUs. Blood was perfused at a wall shear rate of 200 s^–1 for 20 min. Excitation light was applied for 2 s at 1 min intervals. The real–time image was then analyzed at each time point for the percentage of surface area of platelet coverage. Plasma β–thromboglobulin (β–TG) levels were also measured before and after each run. PU–PTMG(650) showed a significantly higher number of adhered platelets than PU–PTMG(2000) at each time point. β–TG levels of PU–PTMG(650) were also higher than those of PU–PTMG(2000), which is comparable to the results of EVM. Thus, this EVM system has been proven to be an excellent and highly sensitive in vitro analytical method for evaluating platelet/biomaterial interactions.     

Synthesis and antitumor activity of tropolone derivatives. 7. Bistropolones containing connecting methylene chains.

Bistropolone derivatives (4-12) containing differing lengths of linkage between the two tropolone rings were prepared and examined for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. Parent compound 3, related compounds previously prepared, and the new compounds 4-12 were evaluated for inhibitory activity against ribonucleotide reductase by indirect means to measure their effects on the dNTP pool imbalance. Present structure-activity relationship results would suggest that potently active bistropolones in vivo inhibit intracellular ribonucleotide reductase through chelating with the two irons at the two active sites of the enzyme.     

Cervical lung hernia in a case of severe chronic asthma and bronchitis

A case of a bilateral pulmonary hernia of the lungs into the supraclavicular fossae is described. A man, aged 79, with severe chronic asthma and chronic bronchitis due to air pollution, complained of a cervical mass off and on for several years. The herniation was greater on the right side. It could be identified on physical examination by the presence of a soft painless supraclavicular bulge which was exaggerated by strain or cough. Radiologically this herniation could best be identified on lateral cervical roentgenogram. It is said that cervical lung hernia is a rare condition, but in our experience supraclavicular herniation of the lung is not unusual in cases of severe chronic obstructive lung disease.     

Rapid detection of mecA gene by nested PCR for diagnosis of methicillin resistance in Staphylococcus aureus]

In recent years, the most common causative organism of hospital infections has been methicillin resistant Staphylococcus aureus (MRSA). The major mechanism of beta-lactam resistance in MRSA is attributed to the production of a specific penicillin binding protein (PBP2'), which is a product of mecA gene, with extremely low binding affinities to beta-lactams. In the present study, we have established a rapid identification method of MRSA by sensitive detection of mecA gene using nested PCR. Nested PCR method amplifying the target DNA in two steps enhanced the efficiency of the second round amplification. By means of this method, mecA gene was successfully detected in clinical samples, such as blood, pus, sputum and feces within 3-4 hrs. Rapid diagnosis of MRSA-bacteremia is particularly important for prevention of sever systemic infection. There are some strains of S. aureus which possess mecA gene in spite of low minimal inhibitory concentration of DMPPC. In these strains expression of mecA gene is induced by contact of beta-lactams and they obtain methicillin resistance. Using nested PCR method, these latent MRSA are rapidly and certainly detectable. This method should be useful for early and effective detection of MRSA hospital infections.     

Endovascular repair of a presumed aortoduodenal fistula.

This report describes the use of transluminal endovascular grafting for the treatment of a presumed aortoduodenal fistula. The patient was a 71-year-old man who had undergone resection and graft replacement for an abdominal aortic aneurysm. Three years after operation, melena was caused by perforation of the duodenal wall by a pseudoaneurysm at the proximal graft anastomosis. The pseudoaneurysm was treated by transluminal endovascular grafting. The pseudoaneurysm was subsequently thrombosed and absorbed. The ulcer-like lesions at the site of the duodenal wall perforated by the pseudoaneurysm also resolved. Endovascular stent-grafts may have a role to play in management of aortoduodenal fistula.     

Surgical repair of total anomalous pulmonary venous connection in neonates and infants--prevention for pulmonary venous obstruction at the site of anastomosis

From October, 1980, to June, 1987, thirty-eight infants less than one year old underwent correction for total anomalous pulmonary venous connection (TAPVC). Overall operative mortality and late mortality were 13% and 6%, respectively. Residual pulmonary hypertension was noted in 4 patients: three had pulmonary venous obstruction at the site of atrial anastomosis (PVOA) and one had supracardiac (Ia) lesion left after repair of mixed type (IV: Ia + III) of TAPVC. Two late deaths occurred in these with PVOA. Twenty-two patients with supracardiac (I) or infracardiac (III) TAPVC were divided into three groups according to the technical development in atrial anastomosis: the large anastomosis in which venous incision reached into at least one pulmonary vein beyond common pulmonary vein and the continuous running suture were used in 10 patients (group 1), the appropriate size of anastomosis in which venous incision limited within the common pulmonary vein and the continuous running suture used in 4 patients (group 2), and the appropriate size of anastomosis and the interrupted suture in 8 patients (group 3). PVOA were 3 (33%) in group 1, but 0 (0%) in group 2 and 3. Two late death occurred all in group 1 with PVOA. Cardiopulmonary bypass time and aortic clamp time in group 3 were 91 min and 74 min respectively, which did not become longer than those in both group 1 and group 2. Interrupted suture technique does not make operating time longer than continuous running suture one. PVOA is one of the important factors predicting late operative result.(ABSTRACT TRUNCATED AT 250 WORDS)     

Placental alkaline phosphatase as a tumor marker for primary intracranial germinoma

A sensitive enzyme-linked immunosorbent assay (ELISA) was used in a retrospective study of placental alkaline phosphatase (PLAP) levels in serum, cerebrospinal fluid (CSF), and intratumoral cyst fluid in primary intracranial germinoma. The ELISA showed no cross-reactivity with intestinal alkaline phosphatase except in very high concentrations, after samples had been heat-treated. Three patients with germinoma were studied for serum PLAP levels and in all the levels were elevated (3.78, 0.52, and 2.11 IU/liter). Two of the germinoma patients were studied for PLAP levels in the CSF, and both had elevated levels (0.83 and 9.83 IU/liter). The intratumoral cyst fluid in one case of germinoma was tested for PLAP and the level was found to be very high (603 IU/liter). These PLAP levels decreased concomitantly with the reduction in tumor size during irradiation. Serum PLAP levels were measured in 40 control adult male individuals and in the CSF of 20 nonpregnant patients with subarachnoid hemorrhage. The upper normal limits were 0.20 and 0.11 IU/liter in the serum and the CSF, respectively. All PLAP levels measured in the serum of patients with various brain tumors were 0.18 IU/liter or less. This study strongly suggests that PLAP is a clinically useful tumor marker for primary intracranial germinoma.