Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Stereotaxic needle localization and biopsy of occult breast lesions: first year's experience.

During a 12-month period 115 patients with abnormal mammograms had stereotaxic needle localization and biopsy of nonpalpable breast lesions. The procedure was performed on a Fischer Mammotest II machine (Fischer Imaging; Denver, CO) and the biopsies were taken with a #18 gauge Bard biopsy needle using a Bard biopty gun (distributed by Bard Urological; Covington, GA; manufactured by Radiplast; Uppsala, Sweden). Mammographic lesions were suspicious matrix densities (85), clustered microcalcifications (22), or a combination of both (8). The pathologist recommended open biopsy in 16 per cent (18/115) of the patients. Pathology on the 18 open biopsies revealed that 11 (9 matrix densities and 2 calcifications) were carcinomas and true positives, whereas the other 7 (all matrix densities) were benign mastopathies and false positives. Further analysis of the pathologic data showed that there were three possible diagnoses from the needle biopsies on the patients that later went to open biopsy: cancer (6), very suspicious lesion (9), and slightly suspicious lesion without atypical hyperplasia (3). All 6 cancers were confirmed by open biopsy; about half (5/9) of the very suspicious lesions were cancer and none (0/3) of the slightly suspicious lesions were cancer. More cases, followed by open biopsy, are needed to refine the selection procedure for open biopsy and careful follow-up of the patients who did not have open biopsy will also be needed to determine the false negative rate. Excellent patient acceptance was found and the test was easy to perform in the office without serious complications. Furthermore, the test was cost effective because it avoided open biopsy in 97 patients.     

Inhibitory effects of AH 21-132 in guinea-pig isolated ileum and taenia caeci.

1. AH 21-132 is being investigated as a potential chemotherapeutic agent for bronchial asthma. The present experiments were designed to determine whether AH 21-132 shares the activity of theophylline as an antagonist at adenosine A1 receptors and to assess its potency as a relaxant in intestinal smooth muscle. 2. In the transmurally-stimulated guinea-pig ileum, theophylline (1 mM), but not AH 21-132 (1 and 10 microM), antagonized twitch depression induced by adenosine. Higher concentrations (100 microM and 1 mM) of AH 21-132 themselves had a depressant effect. Neither theophylline (1 mM) nor AH 21-132 (1 and 10 microM) antagonized twitch depression induced by noradrenaline. 3. AH 21-132 (100 microM and 1 mM) depressed maximum contractions of ileum induced by both acetylcholine (ACh) and histamine. 4. In ileum treated with hyoscine (1 microM), AH 21-132 (greater than 10 microM) caused a concentration-dependent depression of the log concentration-effect curve for potassium chloride. 5. Simultaneous extracellular electrophysiological and mechanical recording from taenia caeci showed that AH 21-132 (100 microM-1 mM) inhibited spontaneous tension waves and their associated bursts of electrical spike activity. 6. Intracellular electrophysiological recording from taenia caeci showed that the mechano-inhibitory effect of 1 mM AH 21-132 was accompanied by abolition of spontaneous spike activity. Following spike abolition, the membrane potential assumed a value very close to that observed during periods of electrical quiescence prior to drug exposure. 7. AH 21-132 inhibited the activity of cyclic AMP-dependent and cyclic GMP-dependent phosphodiesterases derived from homogenates of ileal smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analog language teaching versus natural language teaching: Generalization and retention of language learning for adults with autism and mental retardation

Examined the effects of two instructional methods on language generalization and longterm retention in 23 adults with autism and severe to profound mental retardation. Analog language teaching employed discrete trials in a controlled setting concentrating on discrimination and identification of materials. Natural language teaching emphasized instruction through interactions that occurred incidentally to training students in the use of materials to perform functional tasks. Assessments were conducted under conditions favoring analog teaching to assure against partiality toward natural language teaching. Under such disadvantageous conditions, the methods of natural language teaching would be supported by results showing either no difference or an advantage in their favor. Both techniques increased initial and long-term generalization though the results suggest no relative superiority for either method under these assessment conditions. A significant interaction was found between prior functioning level and sequence of instruction. Because natural language teaching has many strengths, few drawbacks, and produces equal generalization and retention under disadvantageous conditions, it is strongly supported as preferable for people with autism and mental retardation.The authors acknowledge the important assistance provided by the following people: the staff and management of the Behavior Development and Learning Center at CSH/DC directed by Israel Perel, Lisa Kramer, Steve Hafferkamp, James Lowdermilk, and, finally, and especially, to the participants themselves.     

Cephaloridine nephrotoxicity in streptozotocin induced diabetic Fischer 344 (F344) rats

The purpose of this study was to determine if cephaloridine nephrotoxicity is attenuated in streptozotocin (STZ)-induced diabetic rats. Fischer 344 (F344) rats (205-250 g) were given a single injection (i.p.) of STZ (27-35 mg/kg) or citrate buffer. The nephrotoxicity of (750 mg/kg) cephaloridine (i.p.) was then compared with normoglycemic and 14-day diabetic rats. Increased blood urea nitrogen (BUN) levels as well as diminished renal cortical slice accumulation of tetraethylammonium (TEA) and lactate-stimulated p-aminohippurate (PAH) were measured (P less than 0.05) in normoglycemic rats 48 h after cephaloridine administration. Cephaloridine failed to alter BUN levels and organic ion accumulation in diabetic rats. Diabetes did not totally protect against cephaloridine toxicity since kidney weights were elevated in normoglycemic and diabetic rats 48 h after administration of 750 mg/kg cephaloridine. A series of experiments also measured BUN levels, kidney weight and renal cortical slice uptake of PAH and TEA 24, 48 and 72 h after (1500 mg/kg) cephaloridine administration. Cephaloridine increased (P less than 0.05) kidney wt and decreased PAH and TEA uptake (P less than 0.05) in the normoglycemic group at 24-72 h. No change in kidney wt, PAH or TEA uptake was observed in the diabetic rats. These data indicate diabetes reduces cephaloridine nephrotoxicity.     

Cinefluoroscopic evaluation of periprosthetic cardiac valve regurgitation

The results of cinefluoroscopic evaluation in 509 patients in whom there was no evidence of prosthetic mitral or aortic valve regurgitation were compared with those in 41 patients who had perivalvular aortic or mitral regurgitation. Rotational motion of the base ring of each prosthesis (base-ring tilt) was measured in at least two views. A base-ring tilt of 7 degrees or more for aortic prostheses or 11 degrees or more for mitral prostheses was associated with an increased incidence of significant perivalvular regurgitation. Likewise, in patients who had multiple studies, a change between studies in base-ring tilt of 4 degrees or more for aortic prostheses or 5 degrees or more for mitral prostheses was associated with significant perivalvular regurgitation. These data suggest that the presence of either an abnormal base-ring tilt or an abnormal increase in base-ring tilt is strong, supportive evidence of partial prosthetic valve dehiscence.     

Dual function nitroimidazoles less toxic than RSU 1069: selection of candidate drugs for clinical trial (RB 6145 and/or PD 130908.

Following the toxicity and synthetic difficulties encountered with the hypoxic cell radiosensitizer RSU 1069, efforts have focused on development of a superior analogue. Two compounds, RB 6145 and PD 130908, have emerged from this program which overcome the instability and synthetic problems associated with RSU 1069 while retaining favorable biological activity. Both agents show comparable radiosensitizing activity to RSU 1069 following oral or i.p. administration to mice bearing the KHT or RIF-1 tumors. Sensitizing efficiency is about 10 X greater than that observed for misonidazole or etanidazole. Toxicity toward hypoxic tumor cells in vivo is demonstrated by clamping tumors (for 60 min) following administration of PD 130908 or RB 6145. Both are effective hypoxic cytotoxins, but less potent than RSU 1069. Systemic toxicity is substantially reduced following oral drug administration. Further, doses achievable following fractionated drug treatments are sufficiently high to produce significant levels of radiosensitization.