Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer.

BACKGROUND: The one-step nucleic acid amplification (OSNA) assay is a rapid procedure for the detection of lymph node (LN) metastases using molecular biological techniques. The aim of this study was to assess the reliability of the whole sentinel lymph node (SLN) analysis by the OSNA assay as a predictor of non-SLN metastases. METHODS: Consecutive 742 patients with breast cancer were enroled in the study. The association of non-SLN or ≥4 LN metastases with clinicopathological variables was investigated using multivariate logistic analysis. RESULTS: In total, 130 patients with a positive SLN who underwent complete axillary LN dissection were investigated. The frequency of non-SLN metastases in patients who were OSNA+ and ++ was 19.3% and 53.4%, respectively, and that in patients with ≥4 LN metastases who were OSNA+ and ++ was 7.0% and 27.4%, respectively. The cytokeratin 19 (CK19) mRNA copy number (≥5.0 × 10(3); OSNA++) in the SLN was the most significant predictors of non-SLN metastases (P=0.003). The CK19 mRNA copy number (≥1.0 × 10(5)) in the SLN was the only independent predictor of ≥4 LN metastases (P=0.014). CONCLUSION: Whole SLN analysis using the OSNA assay could become a valuable method for predicting non-SLN and ≥4 LN metastases.

Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithelial cells.

We examined the effect of E(2) and selective estrogen receptor modulators (SERMs) on the proliferation and estrogen receptor (ER) activities in normal human prostate cells. SERMs such as toremifene, raloxifene and tamoxifen suppressed the proliferation of prostate epithelial and stromal cells whereas anti-androgens did not. In prostate stromal cells, the transactivation activities of ER were enhanced by adding E(2) and reduced remarkably by toremifene. The results indicate that the ER-mediated pathway plays a central role in the growth of normal prostate cells.

MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas.

BACKGROUND: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC. AIMS: To investigate the prognostic significance of MUC4 expression in IDC. METHODS: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry. RESULTS: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors. CONCLUSIONS: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.

[A case of giant cell tumor originating from the rib].

We have experienced a case of giant cell tumor originating from the rib. A 45-year-old male was admitted to our hospital because of a mass in the left chest wall. A tumor shadow was observed in the left side of chest X ray. Chest CT, bone scintigram showed tumor originating from the left 4th rib. The tumor was suspected giant cell tumor of bone by needle biopsy examination. The tumor was completely resected with chest wall surrounding the tumor. The defect of chest wall was reconstructed with Marlex mesh and the Latissimus dorsi muscle flap. The pathological diagnosis was a giant cell tumor of bone. The patient has been well for two years and one month since surgery, with no signs of recurrence.

[Urethral diverticula surrounding the urethra in women: report of 2 cases].

We report two cases of female urethral diverticula. A 49-year-old woman (case 1) complained of perineal pain when she voided urine. A 36-year-old woman (case 2) complained of perineal pain. In both cases, intravenous pyerography and urethrography revealed diverticula around their urethra, and we diagnosed them with urethral diverticula which surrounded their urethra by magnetic resonance imaging. We treated them by transvaginal diverticulectomy. Case 2 was successfully treated, but the diverticulum recurred after one year in case 1. There are over 200 reported cases of female diverticula in the Japanese literature, but a urethral diverticulum surrounding the urethra is rare.

[Intrascrotal epidermoid cyst: report of two cases].

A 41-year-old man and a 47-year-old man presented with an intrascrotal mass. The routine studies and ultrasonography showed that the mass was not associated with the testis, epididymis or spermatic cord, but the magnetic resonance imaging was the most useful for making a preoperative diagnosis. Both patients received transscrotal resection of the mass, the histopathological diagnosis of which was epidermoid cyst. A total of 24 cases of epidermoid cyst have been reported in the Japanese literature.

Effect of HSR-903, a new fluoroquinolone, on the concentration of theophylline in serum.

The effect of HSR-903, a new fluoroquinolone, on the concentration of theophylline in serum in healthy male volunteers was investigated. The concentration of theophylline in serum and the urinary excretion rates of theophylline on day 5 of concomitant dosing with HSR-903 tended to increase compared to those on day 4, when theophylline was given alone; however, the urinary excretion rates of 1-methyluric acid and 3-methylxanthine on day 5 of concomitant dosing with HSR-903 tended to decrease in comparison to those on day 4, when theophylline was given alone.

[A case of metastatic renal tumor originating from lung cancer difficult to distinguish from renal cell carcinoma].

A 66-year-old female underwent left lower lobectomy for her lung cancer (adenocarcinoma) in November 1992, followed by the resection of brain metastasis in October 1993. Later, a left renal tumor with paraaortic lymph node swelling was found by a follow-up abdominal CT. She was treated with left nephrectomy and the resection of the paraaortic lymph nodes in June 1997. The histopathology of the resected tumor and the lymph nodes revealed a metastatic renal tumor originating from the pulmonary adenocarcinoma. There have been 38 reported cases of metastatic renal tumor from lung cancer in the Japanese literature.

[Experimental mouse models of susceptible and resistant pneumococcal pneumonia with special reference to the cause of bacteremia].

To study the pathogenesis of Streptococcus pneumonieae, we established mouse models with acute pneumonia caused by the penicillin susceptible S. pneumoniae strain (J4) and the clinically isolated penicillin resistant S. pneumoniae (RSTY045). The MICs of the J4 and RSTY045 strain against penicillin G were 0.016 and 2.0 micrograms/ml, respectively. In the therapeutic experiment, the ED50 of penicillin G against the J4 strain was 14,800 IU/kg and that of the RSTY045 strain was 92,000 IU/kg. In the pathological study, both lungs infected with J4 and RSTY045 showed typical bacterial pneumonia. The pathogen infected with the J4 strain showed septic pneumonia in which neutrophils were more invasive to the vascular area than that infected with RSTY045. All of the J4 strain blood cultures tested positive 24 hours into the pneumonia course, whereas only two of the RSTY045 strains showed positive at the end of the pneumonia course. The pneumolysins of J4 and RSTY045 were 191 HU/ml and 1,622 HU/ml respectively. There seemed to be no association between pneumolysin and the blood culture results in our model. To investigate these results, we infected mice with four PSSP and six PRSP clinically isolated strains (RSTY strains) containing J4 and RSTY045, respectively. Blood cultures were performed at 24 hours and 3 days after infection and death rates were calculated 3 days after infection. In the PSSP infection groups, 81.7% showed a positive result at 24 hours and 100% at 3 days after infection showed positive results, whereas in the PRSP 40.0% at 24 hours and 59.0% at 3 days after infection. The average levels of pneumolysin in PSSP and PRSP were 473.0 HU/ml and 835.2 HU/ml, respectively. There seemed to be no association between pneumolysin, death rates and the of blood culture results. (p > 0.05).

[Successful emergency coronary artery bypass grafting in a patient with systemic lupus erythematosus under hemodialysis therapy].

A 38-year-old woman, who had been suffering from systemic lupus erythematosus (SLE) and receiving steroid therapy for the past 25 years, underwent a successful emergency coronary artery bypass grafting for unstable angina. She had also been treated with a 10-year period of hemodialysis therapy for chronic renal failure. Her coronary angiography revealed the heavily calcified ectatic right coronary artery with a thrombus formation in its proximal portion associated with severe stenosis in the proximal left coronary artery. The left internal thoracic artery was anastomosed to #7 and the saphenous vein to #3, respectively. Postoperative coronary angiography performed one month later revealed both grafts to be patent with no stenosis. Ischemic heart disease (IHD) is one of the major complication limiting the prognosis of the patient with SLE. We discuss the point related to cause of IHD and the surgical management.

[A case report of invasive pulmonary aspergillosis which could not be saved in spite of making an early diagnosis].

A seventy-one year old male with pemphigus vulgaris and treated with steroid therapy for long periods of 7 months was suffered from invasive pulmonary aspergillosis. He complained of a productive cough and the chest X-p indicated a mild infiltration shadow in his both lungfields. He was treated by intravenous antibiotics and no clinical improvement was observed. Two days after the onset of the clinical respiratory symptoms, he was transferred to the division of respiratory diseases and the diagnosis of aspergillosis was confirmed by serological and histopathological studies on the same day. Intravenous amphotericin B and oral itraconazole administrations were started immediately after the diagnosis was made. However, the progression of the disease was so rapid and his immune condition was too weak to respond to the treatment. The overall clinical course of the case was extremely short only 5 days.

[A case of pulmonary alveolar proteinosis with high levels of tumor markers].

We report a case of pulmonary alveolar proteinosis (PAP) in which the serum levels of CEA, CA15-3, and TPA, as well as the whole lung lavage fluid levels of CEA, CA19-9, CA125, CA15-3, CA50, SLX, SCC, and TPA were high. The patient was a 39-year-old man who presented with exertional dyspnea, and nonsegmental bilateral reticular infiltration shadows in the middle and lower lung fields on the chest radiograph. A diagnosis of proteinosis was confirmed by histopathology of the transbronchial lung biopsy (TBLB) specimen, biochemical analysis of the phospholipids, and an electron microscopic study of lavage fluid. Whole lung lavages alleviated his symptoms, effaced the shadows on the chest radiographs and brought the blood gas values closer to normal. An immunohistochemical study of TBLB specimens showed that CEA, CA153, and SLX were positively stained in the alveolar epithelia. With repeated lavage, tumor markers (CEA, CA15-3, TPA) in the fluid decreased. These results suggest that the alveolar epithelia indeed produced these tumor marker molecules. In PAP, it is well recognized that CEA may be high in at least one of the following: serum, bronchoalveolar lavage fluid, and whole lung lavage fluid. To date, however, the site of production of such tumor markers had not been clearly demonstrated to be in the lung tissue. This case is interesting because there are few reports of PAP with high levels of tumor markers in the serum and whole lung lavage fluid, and because the tumor markers found in abnormally high amounts in this patient were produced by alveolar epithelia.

[A case of pseudoxanthoma elasticum underwent coronary artery bypass grafting].

A case of pseudoxanthoma elasticum (PXE) underwent coronary artery grafting is reported. Coronary angiography of a woman with age of 41 with PXE revealed three vessels lesions. Coronary artery bypass grafting using saphenous vein grafts was performed. The left internal mammary artery was not able to use because of obstruction. Her postoperative course is uneventful for 3 years to date. Histological examination of a segment of ascending aorta revealed changes of PXE underwent CABG is extremely rare. This is the third reported case in Japan.

[A case of Aspergillus niger pneumonia cured with an early diagnosis].

We have experienced a case with A. niger aspergilloma who developed Aspergillus pneumonia after bacterial pulmonary infection. Examinations of sputum cytology and detection of serum Aspergillus antigen were useful for an early diagnosis of his condition. Early and intensive antifungal chemotherapy mainly with intravenous amphotericin B brought about his complete remission.

Synthesis and pharmacological evaluation of 7-substituted procaterol derivatives.

A series of procaterol derivatives having a substituent at the 7-position of the carbostyril moiety was synthesized. Halogenation of procaterol and its homologues gave the 7-halogeno derivatives (3). Nitration of the procaterol analogues afforded the 7-nitro derivatives (4), and the catalytic reduction of 4 gave the 7-amino derivatives (5). These compounds showed weak beta-adrenoceptor stimulant activities in anesthetized dog.

A trial of molecular epidemiology using bovine enteroviruses isolated monthly from cattle.

Enteroviruses were isolated monthly for one year from feces in the intestine of 47 cattle. Judging from the isolation panel, it was suggested that endemic infection occurs. Genetic changes of isolated enteroviruses were traced using RNase T1 oligonucleotide fingerprint analysis and nonparametric distance scaling. Using some characteristics transitions of fingerprint patterns we could also trace some strains. These analyses suggested that in some strains drastic genetic changes may occur, which coincide with additional infections transmitted from other cows. Furthermore, it was indicated that the genetic changes of viruses isolated from cow R13 were not very drastic, but genetic changes were drastic for viruses isolated from cow R19. Overall, we could never observe the same fingerprint pattern using RNase T1. This study suggests that genetic changes tend to accumulate as time elapses, and at the same time, infection decreases.

Synthesis of procaterol derivative having a piperidylmethanol group and its beta-adrenoceptor stimulant activities.

A procaterol derivative (6) having a piperidylmethanol group was synthesized by the nucleophilic reaction of a 5-formylcarbostyril derivative with pyridyllithium, followed by selective catalytic reductions to afford the erythro-isomer. Compound 6 showed non-selective beta-adrenoceptor agonist activities like those of l-isoproterenol in an in vivo assay using anesthetized dogs.