Primary leiomyosarcoma. A rare tumor of the adrenal gland

OBJECTIVE: To report on a rare case of primary leiomyosarcoma of the adrenal. To our knowledge, this is the fourth case reported in the literature. METHODS: A patient with primary leiomyosarcoma of the adrenal gland is presented. The clinical features are described, and the diagnostic and therapeutic aspects of this rare primary mesenchymal tumor are discussed. RESULTS/CONCLUSIONS: The aggressive nature and the poor prognosis of this rare tumor type are emphasized.     

The appropriateness of use of percutaneous transluminal coronary angioplasty in New York State

Between 1974 and 1989 we prospectively observed 530 patients with brucellosis. The findings for 62 patients (42 males and 20 females; mean age, 34.7 years) with 63 episodes in which the sacroiliac joint was involved (the most frequent osteoarticular location [11.7%]) were analyzed. Ten of the older patients (mean age, 55.3 years) had concomitant spondylitis. Systemic symptoms were usually important, and characteristic pain and findings of sacroiliitis were observed in approximately 75% of cases. Blood cultures were positive for Brucella melitensis for 44 patients. The most frequent radiographic findings were blurring of articular margins (42 cases) and widening of the sacroiliac space (20 cases). No radiographic anomalies were detected in 13 cases. Results of 99mTc and gallium-67 bone scans were abnormal in approximately 90% of cases (abnormalities were often mild). Overall, clinical, radiographic, and isotopic bone scan findings were sensitive and useful, although they were occasionally minimal or difficult to evaluate, making diagnostic findings confusing or misleading. Brucellar sacroiliitis is a mild disease associated with a good outcome similar to that observed for patients with uncomplicated brucellosis.     

Comparison of left anterior oblique, anterior, and geometric mean methods in gastric emptying assessment of postpancreaticoduodenectomy patients

Although left anterior oblique (LAO) gastric emptying studies appear to be an adequate alternative to geometric mean (GM) measurements in patients with normal gastric anatomy, it is not clear whether they can be used after gastric or duodenal surgery. In this study, dual-phase gastric emptying studies with combined solid-liquid meal were performed in 54 patients who had undergone pancreaticoduodenectomy (Whipple procedure). Gastric emptying was studied with GM, LAO, and anterior (ANT) methods. T1/2 and percent gastric retention at 10, 30, 60, 90, and 120 minutes were calculated. Results from the three methods were compared using correlation analysis and the t test. The t test showed no significant difference in T1/2 and percent retention values between the GM and LAO or ANT views. The solid emptying T1/2 showed a better correlation between GM and LAO values (r = 0.824) than between GM and ANT (r = 0.589). For the liquid T1/2, the reverse was true. Correlation between GM and ANT (r = 0.939) was better than between GM and LAO (r = 0.839); however, both LAO and ANT views correlated well with GM liquid emptying. It is concluded that the LAO view can replace GM gastric emptying methods in postpancreaticoduodenectomy patients for evaluation of both solid and liquid emptying, although the ANT view appears completely adequate for the study of liquid emptying.     

Enantioselective, mechanism-based inactivation of guinea pig hepatic cytochrome P450 by N-(alpha-methylbenzyl)-1-aminobenzotriazole

N-Aralkylated derivatives of 1-aminobenzotriazole are well-established, mechanism-based inhibitors of cytochrome P450 (CYP or P450). In this study, the kinetics of inactivation of CYP2B-dependent 7-pentoxyresorufin O-depentylation (PROD) and CYP1A-dependent 7-ethoxyresorufin O-deethylation (EROD) activities by enantiomers of N-(alpha-methylbenzyl)-1-aminobenzotriazole (alphaMB) were compared. The racemic mixture (+/-)-alphaMB, as well as the enantiomers (-)-alphaMB and (+)-alphaMB, produced a time-, concentration-, and NADPH-dependent loss of PROD and EROD activity in hepatic microsomes from phenobarbital-treated guinea pigs. The rates of PROD inactivation by (-)-alphaMB were significantly faster than for (+)-alphaMB. Consistent with this, the derived maximal kinact was also significantly greater for (-)-alphaMB than for (+)-alphaMB (0.49 vs. 0.35 min-1). In contrast, the concentrations required for the half-maximal rate of inactivation (Ki) were equivalent for (-)-alphaMB and (+)-alphaMB, whereas the degree of competitive inhibition of PROD activity was greater for (+)-alphaMB. No significant differences were found among (-)-alphaMB, (+)-alphaMB, and (+/-)-alphaMB with respect to mechanism-based inactivation (kinact = 0.18, 0.16, and 0.17 min-1, respectively) or competitive inhibition of EROD activity. No differences were found for the maximal extent of PROD or EROD inhibition or the loss of spectral P450 after an extended 30-min incubation with the inhibitors. We conclude that mechanism-based inactivation of guinea pig CYP2B, but not CYP1A, isozymes by alphaMB occurs in a stereoselective manner, most likely as a result of a difference in the balance between metabolic activation and deactivation for the alphaMB enantiomers.     

T lymphocyte responses to anti-neutrophil cytoplasmic autoantibody (ANCA) antigens are present in patients with ANCA-associated systemic vasculitis and persist during disease remission

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel has been identified in the cardiac muscle of a number of mammalian species, including humans. The goal of this study was to begin quantifying the structural requirements necessary for arylaminobenzoate block of the CFTR channel. The cardiac cAMP-dependent Cl- current (ICl) was measured using the whole-cell arrangement of the patch-clamp technique in guinea pig ventricular myocytes during stimulation of protein kinase A with forskolin. At drug concentrations below the IC50 value for channel block, reduction of ICl by the arylaminobenzoates occurred in a strongly voltage-dependent manner with preferential inhibition of the inward currents. At higher drug concentrations, block of both the inward and outward ICl was observed. Increasing the length of the carbon chain between the benzoate and phenyl rings of the arylaminobenzoates resulted in a marked increase in drug block of the channel, with IC50 values of 47, 17, and 4 microM for 2-benzylamino-5-nitro-benzoic acid, 5-nitro-2-(2-phenylethylamino)-benzoic acid, and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), respectively. Increasing the carbon chain length further with the compound 5-nitro-2-(4-phenylbutylamino)-benzoic acid, caused no additional increase in the potency of drug block (IC50 = 4 microM). Inhibition of ICl by the arylaminobenzoates was modulated by the pH of the external solution; increasing the pH from 7.4 to 10.0 greatly weakened NPPB block, whereas decreasing the pH to 6.4 enhanced block. In addition, block of ICl was observed during intracellular dialysis of NPPB, and this action was not affected by raising the external pH.     

Antiasthmatic activity of the second-generation phosphodiesterase 4 (PDE4) inhibitor SB 207499 (Ariflo) in the guinea pig

We evaluated the airway activity of the novel phosphodiesterase type 4 inhibitor SB 207499 [Ariflo; c-4-cyano-4-(3-cyclopentyloxy-4-methoxyp henyl-r-1-cyclohexane carboxylic acid)], in the guinea pig. Ovalbumin (OA)-induced contractions of guinea pig isolated tracheal strips were inhibited by SB 207499 with an EC50 of 1 microM but had little or no effect on exogenous agonist-induced contraction, which suggests that its effect on OA-induced contraction in vitro is primarily due to inhibition of mediator release from mast cells. In anesthetized guinea pigs, SB 207499 inhibited OA-induced bronchoconstriction with i.v. and p.o. ID50 values of 1.7 and 17 mg/kg, respectively. At 1, 3 and 6 hr after SB 207499 (30 mg/kg p.o.), OA-induced bronchospasm was inhibited by 92%, 70% and 58%, respectively, corresponding to elevated plasma concentrations of 1.62 +/- 0.19, 1.65 +/- 0.29 and 0. 93 +/- 0.24 microg/ml, respectively, of SB 207499. SB 207499 also inhibited house dust mite-induced bronchoconstriction (ID50 = 0.9 mg/kg i.v. and 8.9 mg/kg p.o.). In contrast to its lack of bronchorelaxant activity in vitro, SB 207499 inhibited bronchospasm induced by i.v. leukotriene D4 (LTD4) [ID50 = 3 mg/kg i.v.]. The bronchorelaxant effect of i.v.-administered SB 207499 was at least additive with that of salbutamol in reversing infused histamine-enhanced airway tone, but it did not alter base line or enhance salbutamol-induced cardiovascular effects. In conscious guinea pigs, SB 207499 (10 or 30 mg/kg p.o.), 1 hr before antigen or LTD4 challenge, markedly reduced bronchospasm and subsequent eosinophil influx as measured by bronchoalveolar lavage 24 hr after provocation. SB 207499 administered after OA or LTD4 challenge also reduced airway eosinophilia measured at 24 hr after OA challenge or 96 hr after LTD4 challenge. These results, coupled with the broad anti-inflammatory activity of SB 207499 previously described (Barnett et al., 1998), suggest that SB 207499 will be useful in the treatment of asthma and other inflammatory disorders.     

Terminal deoxynucleotidyl transferase expression during neonatal life alters D(H) reading frame usage and Ig-receptor-dependent selection of V regions

During neonatal life, Ig diversity is limited in many respects. The absence of terminal deoxynucleotidyl transferase (TdT) expression with the consequent lack of nontemplated addition during the neonatal period, coupled with the predominant usage of a single D(H) reading frame (RF), leads to severe limitations of diversity in the CDR3 region of Ig heavy (H) chains. The neonatal Ig H chain repertoire is also characterized by restricted V(H) usage, with predominant expression of certain V(H) segments, such as V(H)81x, that are rarely evident during adult life. In this report, we examine the effect of enforced TdT expression on the neonatal repertoire of V(H)81xDJ(H) rearrangements. We find that TdT synthesis abrogates D(H) RF bias during the fetal/neonatal period through a Ig-receptor-independent mechanism. These findings suggest that D(H) RF bias during neonatal life is determined largely by homology-directed joining. We also find that TdT synthesis alters the selection of productively rearranged V(H)81xDJ(H) alleles in the neonatal spleen through a Ig-receptor-dependent mechanism. Analysis of predicted CDR3 amino acid sequences indicates that positive selection of V(H)81x-encoded H chains is correlated with the presence of a consensus sequence immediately adjacent to the V(H) segment. These data support the hypothesis that the CDR3 region is critical in determining the ability of V(H)81x-encoded H chains to form functional receptors that support positive selection of B lymphocytes. Together, our results demonstrate that TdT can indirectly influence the Ig repertoire by influencing both receptor-dependent and receptor-independent selection processes.