Sex hormones and calcium regulating hormones in rheumatoid arthritis

Rheumatoid arthritis (RA) occurred frequently in women. Exogenous estrogen has been reported to alleviate the symptoms of patients with RA. But the implications of sex hormones and immunological abnormalities in RA remain to be elucidated. Therefore, we measured sex hormones (LH, FSH, estradiol, testosterone and prolactin), bone metabolic markers (midregion and carboxy terminal mainly recognized PTH1-84, intact PTH1-84, bone GLA protein and alkaline phosphatase), bone mineral, in lumbal bone with quantitative tomography (QCT) and with of cortex with microdensitometry in 52 females with RA and 46 females with osteoarthritis (OA) as a control group. Sex hormones and bone metabolic markers were analyzed as independent variables of serum LH, FSH and estradiol levels, using one way analysis, in patients with RA and OA. The more increased serum FSH and LH levels were, the more decreased serum estradiol levels were in both RA and OA groups, when they were considered as independent variables. These results indicate that the secretory function of pituitary and ovary axis hormones are normally enacted in RA. On the other hand, when the sex hormones of the patients under 53 years of age were studied in both groups, serum FSH adn LH showed significantly higher levels, while serum estradiol levels revealed decreased tendency in RA, compared with these in RA. Thus the pituitary ovary secretory function in patients with RA was suggested to be disturbed in early stage of age, indicating that the sex hormones would be partly implicated in calcium and bone metabolism in patients with RA.     

Jarcho-Levin Syndrome Associated with Atrial Septal Defect and Partial Anomalous Pulmonary Venous Return: A Case Report

A bstract A 61-year-old woman suffering from Jarcho-Levin syndrome (JLS) was associated with atrial septal defect and partial anomalous pulmonary venous return and underwent corrective surgery. Pressure controlled postoperative ventilator therapy is preferred in patients with JLS.     

Persistent left superior vena cava draining to left atrium with normal coronary sinus

In embryology, a persistent connection of the left superior vena cava to the left atrium rarely coexists with a coronary sinus. We herein report an unusual case of persistent left superior vena cava terminating in a left atrium with normal coronary sinus, which was revealed at the time of permanent pacemaker implantation after a second operation for recurrent left atrioventricular valve regurgitation. Because this anomaly had gone undiagnosed at the first operation, we were unable to diagnose it prior to the second operation, because the preoperative coronary angiogram clearly demonstrated a coronary sinus that was not dilated. We would have repaired the anomaly using a patch or other procedure had it been diagnosed before the second operation in order to prevent cyanosis or brain complications secondary to right-to-left shunting. One should always be on guard for this rare condition.     

Blockade of superoxide generation prevents high-affinity immunoglobulin E receptor-mediated release of allergic mediators by rat mast cell line and human basophils

BACKGROUND: Previous studies have shown that rat peritoneal mast cells and mast cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular reactive oxygen species (ROS) in response to antigen challenge. However, the physiological significance of the burst of ROS is poorly understood. OBJECTIVE: The present study was undertaken to investigate the role of superoxide anion in mediator release in rat and human cell systems. METHODS: RBL-2H3 cells were directly stimulated with anti-rat FcepsilonRI alpha-subunit monoclonal antibody (mAb). For the analysis of human cell system, leucocytes were isolated by dextran sedimentation from healthy volunteers or from patients, and challenged either with anti-human FcepsilonRI mAb or with the relevant antigens. Superoxide generation was determined by chemiluminescence-based methods. The releases of histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben assay (ELISA). RESULTS: Cross-linking of FcepsilonRI on RBL-2H3 cells or on human leucocytes from healthy donors by the anti-FcepsilonRI mAb resulted in a rapid generation of superoxide anion, as determined by chemiluminescence using superoxide-specific probes. Similarly, leucocytes from patients generated superoxide anion in response to the challenge with the relevant allergen but not with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well-known inhibitor of flavoenzymes suppressed the superoxide generation and the release of histamine and LTC4 induced by the anti-FcepsilonRI mAb or by allergen in parallel. CONCLUSION: These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon FcepsilonRI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders.     

The effect of protein restriction on the severity and recovery from ischemic renal failure

The effects of chronic dietary protein restriction on ischemic renal failure were evaluated in rats subjected to 90 min of bilateral renal clamping. The rats were kept on either 20% casein (regular) diet or casein-free (protein-free) diet 10 days before and 21 days after renal injury. Rats on regular protein diet showed higher levels of BUN and serum creatinine and had a lower inulin clearance (microliter/min/100 g BW) than animals on protein-free diet (289 +/- 34 vs 582 +/- 103, p less than 0.05) 2 days after ischemia. However, the inulin clearance measured 21 days following ischemia was significantly higher in rats on regular diet (1468 +/- 181) than those maintained on protein-free diet after ischemia (560 +/- 167). When unilateral 90 min ischemia was performed in rats on regular diet, the postischemic kidneys showed an incomplete recovery of the inulin clearance (226 +/- 35) compared to the contralateral kidney (900 +/- 116), 21 days after ischemia; whereas in rats on a protein-free diet the inulin clearance averaged 106 +/- 17 in the postischemic kidney and 345 +/- 41 in the right kidney. When left renal ischemia and contralateral nephrectomy were performed, the inulin clearance was 1149 +/- 74 in rats on regular diet and 534 +/- 60 in rats on protein-free diet, 21 days following renal insult. These results suggest that protein restriction can play a protective role against renal ischemia in an initial phase, but it limits the late recovery from ischemia. The presence of a normal contralateral kidney inhibits the functional recovery of the postischemic kidney and a contralateral nephrectomy produces a compensatory functional hypertrophy of the postischemic kidney, even in rats on a protein-free diet.     

Isolation and preliminary characterization of ACNU-resistant sublines of rat brain tumors in vivo.

Two variant cells lines resistant to the nitrosourea derivative ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), namely C6/ACNU and 9L/ACNU, were selected in vivo from rat brain tumors. Stable resistance to ACNU proved to be a characteristic of these cell lines, whether they were grown in vivo or in vitro. These cell lines exhibited a different pattern of cross-resistance to a wide range of chemotherapeutic agents with dissimilar chemical structures and mechanisms of action as compared with that of other ACNU-resistant cell lines established in vitro. Distinct cross-resistance was observed in both the C6/ACNU and 9L/ACNU cell lines to chloroethyl-nitrosoureas such as BCNU (carmustine), CCNU (lomustine), and methyl CCNU and, additionally, to vincristine, vinblastine, Adriamycin (doxorubicin), and arabinosylcytosine, but not to bleomycin, methotrexate, cis-platinum, and 5-fluorouracil. This might point to a multifactorial mechanism of drug resistance in ACNU-resistant cell lines derived from rat C6 and 9L brain tumor cells.     

Effect of smoking on fibronectin production by human amnion and placenta.

Fibronectin production from amnion and placental tissues was evaluated in pregnant woman smokers and nonsmokers in order to examine if there were alterations of fibronectin metabolism in intrauterine tissues. In both amnion and placental tissues, cycloheximide inhibited the fibronectin output indicating that it was being synthesized. Mean fibronectin output by amnion in pregnant woman smokers was significantly lower than that in pregnant woman nonsmokers. In contrast, in the placenta from pregnant woman smokers, the output was significantly higher than that in pregnant woman nonsmokers. The present observations indicate that smoking alters an important biochemical constituent in amnion and placenta, possible leading to some complications.     

Alterations of nuclear pores in preneoplastic and neoplastic rat liver lesions induced by 2-acetylaminofluorene

The nuclear pore density and area were measured on freeze-fracturednuclei of ACI/N rat liver altered foci, adenomas and carcinomasinduced by 2-acetylaminofluorene, and compared with those ofnormal hepatocytes. The pore density of nuclei from these preneoplasticand neoplastic lesions was significantly higher than that ofhepatocytes, but there was no difference between lesions. Thearea of nuclear pores of the focus cells did not differ fromnormal hepatocytes, whereas the areas of pores of adenoma andcarcinoma cells were increased. Moreover, the nuclear pore areaof carcinomas was significantly greater than that of adenomas.These results suggest that some changes may occur in nuclearpores in the progress of tumorigenesis.     

Myocardial perfusion and clearance of 99mTc teboroxime assessed by SPECT]

99mTc teboroxime is a new myocardial imaging agent that has characteristics of high accumulation in the heart and rapid clearance. We performed tomographic teboroxime study and compared the findings with that of 201Tl. Myocardial teboroxime clearance was calculated by dynamic single photon emission computed tomography (SPECT) using continuous repetitive rotation acquisition method. Teboroxime SPECT image was reconstructed by the three-minute data started from 4 minutes after injection. In 45 myocardial regions (15 patients), complete agreement between 201Tl and 99mTc teboroxime was obtained in 33 regions (73%), when the findings were classified as normal, ischemia and infarction. Significant delay in clearance was seen in the region of coronary stenosis (greater than or equal to 75%) compared with that in the control region (p = 0.0087 at rest, and p = 0.0385 at peak exercise by paired T test). Septum-to-lateral ratios of the clearance and myocardial initial count showed positive correlation (r = 0.743). Further clinical application of this radiopharmaceutical is expected as a new myocardial imaging agent.