Clinical Evaluation of an Immunoradiometric Assay for CA15-3 Antigen Associated With Human Mammary Carcinomas: Comparison With Carcinoembryonic Antigen

Serum levels of CA15-3, a mammary tumor associated antigen recognizedby two different murine monoclonal antibodies (115D8 and DF3),were investigated in patients with mammary carcinoma and otherbenign or malignant diseases. The reference value of the serumCA15-3 level was obtained as 24 units/ml at the 99% confidencelimit among healthy individuals (n = 462). Elevation of serumCA15-3 levels was observed in 24.3% of overall patients withmammary carcinoma. Serum CA15-3 levels in breast cancer patientscorrelated with the clinical stage; higher percentages of positivitywere observed in those with advanced breast cancer (stage IV,64.7%, recurrent, 52.4% and metastatic, 70.3%). Furthermore,elevated serum CA15-3 levels in breast cancer patients respondedwell to the effect of therapy. Although the serum CA15-3 testgave percentages of positivity of breast cancer similar to thosefound by the serum CEA test, the serum CA15-3 test revealedlower percentages of posi-tivity than the serum CEA test amongpatients with benign breast lesions, liver cirrhosis or othercarcinomas. These results suggest that the serum CA15-3 antigenlevel provides a very useful marker for diagnosis and clinicalmonitoring of patients with breast cancer.     

Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo

PURPOSE: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. MATERIALS AND METHODS: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n=6-8). RESULTS: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 micromol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 micromol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%]=growth of TAK-165 treated tumor/average growth of control tumorx100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. CONCLUSIONS: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer.     

Effectiveness of prosthetic mandibular advancement for obstructive sleep apnea:Analysis by sleep position

Abstract Fifteen patients with obstructive sleep apnea were treated using prosthetic mandibular advancement (PMA). Each patient was evaluated in the supine and lateral decubitus positions with and without PMA. After PMA treatment, the mean intraesophageal pressure (Peso) in the supine position improved from -42.6 to -27.3 cmH₂O and the mean apnea + hypopnea index (AHI) decreased from 48.8/h to 23.7/h. The mean Peso in the lateral decubitus position improved from -27.9 to -18.6 cmH₂O and the mean AHI decreased from 9.6/h to 6.6/h. With PMA, respiratory disturbance during sleep further improved by changing the body position from the supine to lateral decubitus position.     

Epstein-Barr Virus in Normal Pregnant Women*

ABSTRACT: Acquired immune suppression accompanying normal pregnancy may be associated with reactivation of Epstein-Barr virus (EBV). Pregnant women with reactivated EBV having anti-EA antibodies show high titers of antiviral capsid antigen (VCA) geometric mean titers (GMT) of 522 versus 170 in those lacking anti-early antigen (EA). Among twenty-seven seropositive women at parturition, 17 (63%) had generated antibody to EA, and all 27 (100%) demonstrated significant increases in antibody to VCA (p < 0.01). In contrast, antibody titers to cytomegalovirus, herpes hominis, varicella-zoster, and rubella viruses in the pregnant women were comparable to those found in nonpregnant controls.     

Natural Killer Activity and Antibody-Dependent Cell-Mediated Cytotoxicity in Multiple Myeloma

Natural killer (NK) activity and antibody-dependent cell-mediatedcytotoxicity (ADCC) were studied by routine methods in 11 patientswith untreated malignant monoclonal gammopathy. NK and/or ADCCactivity was clearly reduced in three patients with advanceddisease. Moreover, sera from some myeloma patients impairedthe ADCC and NK activity. A large quantity of purified monoclonalIgG from one patient appeared to inhibit NK and ADCC activityas did high concentrations of pooled polyclonal immunoglobulinfrom healthy persons. In two of these 11 patients, other malignancieswere diagnosed prior to chemotherapy. One of these patients,who had nonsecretory myeloma, had marked impairment of NK andADCC activity; the other, with IgG myeloma, had normal NK andADCC activity.     

ADDITIONAL PROOF OF REDUCTION OF ETHANOL ABSORPTION FROM RAT INTESTINE IN VIVO BY HIGH ACETALDEHYDE CONCENTRATIONS

We investigated intestinal ethanol absorption in rats pretreatedwith saline, cyanamide, 4-methylpyrazole and cyanamide + 4-methylpyrazole.The value of the absorption rate constant in the cyanamide-pretreatedgroup with high acetaldehyde levels was the lowest among thefour groups, but there were no significant differences amongthe remaining groups. We found that high acetaldehyde concentrationitself clearly reduces intestinal ethanol absorption.     

Multivariate autoregressive analysis of carotid artery blood flow waveform in an infant of a diabetic mother with cardiomyopathy

We analyzed the carotid artery blood flow waveform (CABFW) of an infant of a non-insulin dependent diabetic mother with hypertrophic cardiomyopathy (IDM cardiomyopathy) through multivariate autoregressive analysis and compared the developmental change of his CABFW with that of normal newborns. The total power was lower than normal newborns on the second and third day of life when his heart dysfunction was severe, and elevated on the fifth day of life when normal-heart function was recovered. The power of component 3 (C3), of which the damping frequency was 7–11 Hz, was slightly high on the second and third day of life and it decreased to the normal range on the fifth day of life by component analysis. In contrast, the power of C3 increased with decreasing resistance index of anterior cerebral artery (RI of ACA) which shows the cerebral vascular resistance of normal newborns. These results suggest that the carotid artery blood flow volume decreased by low cardiac output and the cerebral vascular resistance decreased to maintain the cerebral circulation, when the heart dysfunction was severe.     

PREVALENCE OF EYELID DERMATITIS IN PRIMARY SJÖGREN'S SYNDROME

Background. The eyelid dermatitis seen in elderly patients is a relatively heterogenous and troublesome disease. Most cases seem to be idiopathic and show resistance to standard dermatologic therapy. Methods. Fifty-two patients with primary definite Sjögren's syndrome (4 men, 48 women, mean age 54 years) were enrolled in this study, and the prevalence of eyelid dermatitis was investigated. Diagnostic criteria for Sjögren's syndrome were based on the criteria proposed by the Japanese Ministry of Health and Welfare. Patch test was performed using ICDRG-European standard allergens and/or eye drops, hair dye, and cosmetics. Results. Of the 52 patients, 22 showed eyelid dermatitis. These changes were much more frequent in elderly patients and showed a good correlation with the presence of ocular dry sensation. No significant difference was observed in clinical and other laboratory findings between patients with or without eyelid dermatitis. Although 8 of the 13 patients showed positive patch test reaction to various allergens, no close relationship existed between the use of a suspected substance and the onset or severity of eyelid dermatitis. Conclusions. These results suggest that the presence of rubbing dermatitis of the eyelid may be one of the cutaneous manifestations of Sjögren's syndrome.     

A case of pelvic malignant paraganglioma

We report a rare case of pelvic malignant paraganglioma that was treated with surgery, combination chemotherapy and radiation. A 47-year-old man was diagnosed with pelvic malignant paraganglioma that had metastasised to the thoracic vertebrae. The pelvic mass, which was 6 cm in size, was on the posterior side of the bladder and had invaded the prostate, seminal vesicle and bladder neck. We resected the intrapelvic tumor and lymph nodes using cystoprostatectomy. Metastases to bilateral obturator lymph nodes and the right internal iliac lymph node were shown by pathology. Adjuvant therapies included six courses of the combination chemotherapy (cyclophosphamide, vincristine and dacarbazine), and 12 courses of VP-16 therapy. Radiation therapy was done for metastasis of the thoracic vertebrae. Local recurrence, progression of bone metastasis and new metastasis have not been detected since these treatments. The patient has been clinically stable during 20 months of follow-up. Chemotherapy of cyclophosphamide, vincristine and dacarbazine and VP-16 with radiation appears to be effective in treating advanced malignant paraganglioma.     

Detection of apoptosis in keloids and a comparative study on apoptosis between keloids, hypertrophic scars, normal healed flat scars, and dermatofibroma

Recent studies have suggested that the regulation of apoptosis during wound healing is important in scar establishment and the development of pathological scarring. In this study, we demonstrate that keloid fibroblasts can be identified as apoptotic cells because of their highly condensed chromatin and discrete nuclear fragments. To further reveal the phenomenon of apoptosis, we quantified the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in surgically resected tissues of keloids (N = 10), hypertrophic scars (N = 10), normal healed flat scars (N = 10), and dermatofibroma (N = 10). The number of TUNEL-positive cells was relatively low, but was significantly higher for the keloid group compared with the normally healed flat scar group (p = 0.004), suggesting reduced cell survival and increased apoptotic cell death in a subpopulation of keloid fibroblasts. Furthermore, the number of TUNEL-positive cells was significantly higher for the keloid group compared with the dermatofibroma group (p = 0.044), suggesting that a subpopulation of keloid fibroblasts may suppress tumorgenicity at a greater rate than dermatofibroma by undergoing cell death. Hypertrophic scars had significantly higher levels of apoptosis than normally healed flat scars (p = 0.033). Therefore, these results suggest that selected fibroblasts in keloids and hypertrophic scars undergo apoptosis, which may play a role in the process of pathological scarring.