Assessment of affinities of propranolol and bopindolol to membranes from COS-7 cell transiently transfected with beta-1- and beta-2-adrenoceptors using a radioligand-binding assay method.

This study was performed to assess the affinities of propranolol, bopindolol, its two metabolites (18-502, 20-785), pindolol, metoprolol, and atenolol to beta(1)- and beta(2)-adrenoceptor (beta(1)- and beta(2)-AR) subtypes using the membranes of COS-7 cells transiently expressing beta(1)- and beta(2)-AR subtypes. Radioligand-binding assays were performed and the results were compared with those (pKi or pA(2) values) obtained from the membrane-enriched fractions from the rat heart, cerebral cortex, bovine heart, tracheal smooth muscle or guinea-pig heart muscle. The pKi values of propranolol, bopindolol, its two metabolites, atenolol, pindolol and metoprolol to beta(1)-AR subtypes obtained from COS-7 cell membranes were 9.02 +/- 0.04, 7.44 +/- 0.12, 9.38 +/- 0.31, 6. 65 +/- 0.16, 5.55 +/- 0.14, 8.17 +/- 0.15 and 5.99 +/- 0.13, respectively. The rank order of pKi values for these agents to beta-(2)-ARs in COS-7 cell membranes was the same as that of beta(1)-ARs. In addition, good correlations were observed between pKi values of homogenates from various tissues and those of transfected COS-7 cell membranes to beta(1)- and beta(2)-ARs. Although good correlations were also observed between pA(2) values obtained from tracheal smooth muscle (beta(2)-ARs) and pKi values obtained from transfected COS-7 cell membranes to beta(2)-ARs, low correlation coefficient values to beta(1)-ARs were observed, however. In conclusion, these results suggested that binding characteristics of (3)H-CGP-12177 to beta-AR subtypes in these membranes from transfected COS-7 cells are similar to those from membrane fractions of various tissues.

[Prospective matched control study concerning the treatment and quality of life of hemophiliacs with inhibitors].

Factor VIII (IX) inhibitors represent one of the most serious problems for the treatment of patients with hemophilia. The Blood Products Research Organization (Japan) has supported a study group for treatment of hemophiliacs with inhibitors. In 1995 the study group started a prospective matched control study of hemophiliacs with and without inhibitors and compared such factors as quality of life and economic cost. Each inhibitor patient was matched with a control patient in terms of age, type of hemophilia, and severity of hemophilia. A total of 136 patient-pairs were enrolled. Bleeding episodes were more frequent in the control group than in the inhibitor group. Days of hospitalization, days in wheelchairs, and the number of impaired joints were significantly higher for the inhibitor group. Number of blood-product infusions, days of bed rest at home, and days of brace use were the same for both groups. Blood-product expenditures were significantly higher for the inhibitor group than for the control group (yen 10,872,283/patient/year vs. yen 4,327,542/patient/year). Our study highlighted the higher cost of treatment and lower quality of life for hemophiliaes with Factor VII inhibitors.

Basal cell adenocarcinoma of the salivary glands: comparison with basal cell adenoma through assessment of cell proliferation, apoptosis, and expression of p53 and bcl-2.

BACKGROUND: Basal cell adenocarcinoma (BCAC) of the salivary gland is a rare tumor and recently described entity. Eleven cases of BCAC are presented here and compared with basal cell adenoma (BCA) through assessment of cell proliferative activity, apoptosis, and expression of p53, bcl-2, and epidermal growth factor receptor (EGFR) because these two tumors show close similarity in some cytologic and architectural characteristics. METHODS: Formalin fixed, paraffin embedded sections of 11 cases of BCAC and 9 cases of BCA, selected from the authors' files of 1851 primary tumors of the major salivary gland, were examined using immunostaining for Ki-67 (MIB-1), p53, bcl-2, and EGFR. In addition, apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling. RESULTS: The incidence of BCAC was 0.6% among patients with major salivary gland tumors in the current series. Nine cases of BCAC arose in the parotid gland and two were of submandibular gland origin. Approximately 50% of the patients had recurrences, but no patient developed metastases or died of disease. Vascular involvement (75%), perineural invasion (36%), and necrosis (45%) were common features. Cell proliferative activity, including mitotic count, Ki-67 labeling index (LI), and apoptotic index were significantly higher in BCAC than BCA. More than four mitotic figures per ten high-power fields or a Ki-67 LI > 5% appeared to be limited to cases of BCAC. Considering those cases expressing p53 or EGFR in > 10% of tumor cells as positive, 6 of the 11 BCAC cases were positive for p53 and 3 were positive for EGFR. In contrast, all BCA cases were negative for p53 and EGFR. Although all cases of BCA were strongly positive for bcl-2 (> 50% of tumor cells), 3 of 11 cases of BCAC were completely negative. CONCLUSIONS: BCAC is a rare salivary gland tumor with a relatively high recurrence rate. Examination of cell proliferation, apoptosis, and expression of p53, bcl-2, and EGFR were found to be useful in distinguishing malignant basal cell tumors from their benign counterparts arising in the salivary gland.

[Nutritional and immunological assessment in patients with malignant obstructive jaundice--the influence of preoperative biliary decompression and abdominal surgery].

A clinical study was undertaken to evaluate the nutritional and immunological status of patients with malignant obstructive jaundice with serum bilirubin level of 5mg/dl or greater (N = 22). Healthy volunteers (N = 9) and patients with cholecystolithiasis (N = 26) were assessed as non-icteric control, as well as patients with obstructive jaundice due to choledocholithiasis (N = 3) were used as icteric control. We also evaluated the time-course of five patients with malignant obstructive jaundice before and after PTCD and surgery. Nutritional status was assessed by prognostic nutritional index (PNI), blood chemistry and rapid turnover protein. Cellular and humoral immunity were assessed by peripheral lymphocyte count, lymphocyte stimulation test, antibody dependent cell-mediated cytotoxicity, and serum immunoglobulins. The following results were obtained. 1) Nutritional and immunological status of patients with malignant obstructive jaundice were severely depressed. 2) Nutritional and immunological status were not improved by preoperative biliary decompression such as PTCD. 3) The immunological indices recovered postoperatively. However, the nutritional indices did not recover by the time of discharge. Intensive nutritional support before and after surgery may be mandatory for patients with malignant obstructive jaundice.

Teratogenic potency of 2,3,4,7,8-pentachlorodibenzofuran and of three mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans in mice. Problems with risk assessment using TCDD toxic-equivalency factors.

The potency of 2,3,4,7,8-pentachlorodibenzofuran (P5CDF) and of three defined 2,3,7,8-TCDD-free mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs) to induce cleft palates in NMRI mice was studied. The data were compared with a dose-response curve for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The slope of the dose-response curve for P5CDF was the same as for TCDD. However, application of the International-TCDD-Toxic-Equivalency (I-TE) factor (NATO/CCMS 1988) of 0.5 overestimated the potency of the pentachlorinated congener about 2.5-fold under these experimental conditions, suggesting 0.2 as a TE factor. When assessing the cleft palate frequency on the basis of I-TEs and the weight of the substances, the potencies of the two PCDF mixtures studied were also clearly overestimated. This result was not substantially changed when using the TE factor of 0.2 for P5CDF. For the PCDD mixture studied, the cleft palate-inducing potency found largely agreed with the prediction when applying the I-TE factors. According to our data, the use of TE factors as calculated by the UBA/BGA (1985) or the NATO/CCMS (1988) are both conservative when attempting to assess the cleft palate incidence induced by PCDF mixtures in mice.

[Preoperative assessment of risk for gastroenterological operations in patients with hepatic cirrhosis].

In order to devise an easy and available method to assess the surgical risk of cirrhotic patients, we reviewed 52 cirrhotic patients who underwent gastroenterological operations at Tokyo Kosei Nenkin Hospital between 1968 and 1982, by means of multivariant discriminant analysis. Utilizing presence of ascites, serum albumin, ICG R15, prothrombin time and platelet count, we estimated the surgical risk as Risk Score. Furthermore, our method predicted short-term survival of other 150 cirrhotic patients who underwent gastroenterological operations at the First Surgical Department The University of Tokyo between 1968 and 1985. We conclude that our method is easily available, and that cirrhotic patients with Risk Score less than or equal to 2.5 tolerate all the gastroenterological operations except hepatic major resection, and that those with Risk Score of residual liver less than or equal to 2.5 tolerate well hepatic major resection.

[An assessment of outcome prediction in patients with severe brain damage with auditory brainstem response and blink reflex].

Results of auditory brainstem response (ABR) and electrically elicited blink reflex (BR) recorded from 43 patients with severe brain damage within three days after the onset of illness were analyzed to assess the prognostic value of ABR and BR with respect to patient outcome evaluated by the criteria proposed by Jennett and Bond. It was possible to recognize, in recordings obtained from patients with severe brain damage, three basic patterns of BR as well as five patterns of ABR within three days after the onset. Three basic patterns of BR were composed of Type I, which closely approximated the BR of normal subjects except for moderately prolonged latency of R2, Type II, which indicated absence of bilateral R2 activities, and Type III, which showed absence of R1 as well as bilateral R2. ABRs were graded, in increasing order of abnormality, from Type I to Type V. Type I was almost normal pattern from wave I to wave V. Type II indicated prolonged latency or markedly reduced amplitude of waves IV and V. Type III showed absence of waves IV and V. Type IV had only wave I. Type V indicated absence of all waves. BR abnormalities significantly proved useful in predicting vital prognosis of the comatose patients with supratentorial lesion. In patients who had Type II of BR, additional studies of ABR enhanced the reliability of prediction of functional prognosis. On the other hand, ABR was recognized as stronger basis for predicting outcome in patients with infratentorial lesion. All patients with Type IV or Type V of ABR were expired within one month after the onset.(ABSTRACT TRUNCATED AT 250 WORDS)