Aminopeptidase N purified from gypsy moth brush border membrane vesicles is a specific receptor for Bacillus thuringiensis CryIAc toxin

We have evaluated the binding of Bacillus thuringiensis Cry toxins to aminopeptidase N (APN) purified from Lymantria dispar (gypsy moth) brush border membrane vesicle (BBMV). CryIAc toxin bound strongly to APN, while either the structurally related CryIAa and CryIAb toxins or CryIC, CryIIA, and CryIIIA toxins showed weak binding to APN. An in vitro competition binding study demonstrated that the binding of CryIAc to L. dispar BBMV was inhibited by APN. Inhibition of short circuit current for CryIAc, measured by voltage clamping of whole L. dispar midgut, was substantially reduced by addition of phosphatidylinositol-specific phospholipase C, which is known to release APN from the midgut membrane. In contrast, addition of phosphatidylinositol-specific phospholipase C had only a marginal effect on the inhibition of short circuit current for CryIAa. These data suggest that APN is the major functional receptor for CryIAc in L. dispar BBMV. A ligand blotting experiment demonstrated that CryIAc recognized a 120-kDa peptide (APN), while CryIAa and CryIAb recognized a 210-kDa molecule in L. dispar BBMV. In contrast, CryIAa and CryIAb bound to both the 120- and 210-kDa molecules in Manduca sexta BBMV, while CryIAc recognized only the 120-kDa peptide. The 120-kDa peptide (APN) in L. dispar BBMV reacted with soybean agglutinin, indicating that N-acetylgalactosamine is a component of this glycoprotein.     

Percutaneous treatment of bronchial artery aneurysm with use of transcatheter coil embolization and thoracic aortic stent-graft placement

Lactic acidosis due to thiamine deficiency is known to complicate chemotherapy and radiotherapy treatment of malignant extracranial tumors, but to the authors' knowledge, this complication has not been reported in patients treated for malignant brain tumors. They report three such cases, demonstrating that this complication can occur during treatment of brain tumors. In all patients, consciousness levels deteriorated within 1 to 2 days. Serum lactic acid levels increased to concentrations between 62 and 96.7 mg/dl, resulting in severe metabolic acidosis. A low blood thiamine level (9 ng/ml) was demonstrated at the onset in one case, and high-dose thiamine infusions dramatically improved lactic acidemia as well as impairment of consciousness in two cases. In the other case, hydrocephalus was suspected initially, resulting in a delay in thiamine supplementation. Clinical differentiation of this form of lactic acidosis from hydrocephalus or tumor progression can be very difficult in a patient undergoing treatment for a malignant brain tumor. Demand for thiamine is thought to be increased in patients with malignant brain tumors, and supplemental thiamine during treatment is necessary to prevent lactic acidosis. When this complication occurs, immediate treatment with sufficient thiamine is essential, together with normalization of pH by using sodium bicarbonate. With timely intervention, the level of consciousness can recover to the preacidotic state with no new neurological deficits.     

Cytogenetically unrelated clones in therapy-related myelodysplasia and acute myeloid leukemia: experience from the Copenhagen series updated to 180 consecutive cases

Among Callitrichids, scent secretions have been identified as carrying information regarding species, subspecies, gender, social status, individuality, hormonal status, and timing of ovulation. We propose that information regarding familiarity and reproductive status is also communicated. Seven male-female pairs of cotton-top tamarins (Saguinus oedipus oedipus) were presented with several drops of distilled water, a scent secretion from the female of that pair, scent secretions from unfamiliar, reproductively mature but noncycling females, and scent secretions from unfamiliar, reproductively cycling females. Behavioral responses from both males and females were recorded over a 10 min period. Differences in behavioral response for both males and females were significant across all four conditions. This indicates that cotton-top tamarins are capable of discriminating a familiar scent from an unfamiliar scent as well as the reproductive status of an unfamiliar female. The communication of this information may play an important role in regulating mate selection, reducing reproductive competition, and stabilizing transfers in and out of groups in the wild.     

Can adrenal incidentalomas be safely observed?

We currently recommend excision of adrenal incidentalomas > or = 4 cm in size and all hormonally active tumors. The optimal management and follow-up of smaller nonfunctioning tumors are controversial. The aim of this study was to determine the clinical outcome of a well defined population of patients with incidentalomas followed without operative intervention. The study group comprised 231 patients, identified from the records of abdominal or thoracic computed tomographic (CT) scans performed between 1985 and 1989. The primary outcome variable analyzed was survival. Follow-up was obtained by office records, telephone contact, or letter. There were 101 male and 130 female patients with a mean age at diagnosis of 64 years (range 5-86 years). Most adrenal tumors were unilateral (right 113; left 98); 20 were bilateral. Mean tumor size was 2 cm (range 1-6 cm). In nine (4%) patients the tumor was > or = 4 cm. Follow-up [mean 7 years; range 1 month (patient died) to 11.7 years] was complete in 224 (97%) patients. Ninety-one (39%) patients had one or more additional CT scans performed during the follow-up period, with only four patients demonstrating a > 1 cm increase in the size of the adrenal mass. Surgical excision of these four lesions identified benign pathology. Eighty-one (35%) patients died of conditions unrelated to adrenal pathology. No patient developed subsequent adrenal hyperfunction or adrenal malignancy. Within the context of our guidelines, conservative management of adrenal incidentalomas considered benign or nonfunctioning at diagnosis is appropriate. Additional information provided by repeat CT scanning appears to confer limited benefit. This study does not support laparoscopic removal of small, nonfunctional adrenal tumors, as has been suggested.     

Bone density and fracture risk in men

We evaluated different definitions of osteoporosis in a population-based sample of 348 men (age 22-90 years) compared with 351 women (age 21-93 years). Thirty-six men (10%) and 46 women (13%) had a history of osteoporotic fracture (hip, spine, or distal forearm due to moderate trauma at >/= age 35). In logistic regression analysis, osteoporotic fracture risk was associated with bone mineral density (BMD) at all sites (neck, trochanter, total hip, lumbar spine, and total wrist) in both genders (p < 0.001) except spinal BMD in men. After adjusting for age, total hip BMD was the strongest predictor of fracture risk in women (odds ratio [OR] per 1 SD decline, 2.4; 95% confidence interval [CI], 1.6-3.7), while wrist BMD was best in men (OR, 1.5; 95% CI, 1.1-2.0). Among men but not women, bone mineral apparent density (BMAD) was a better predictor of fracture than BMD (wrist BMAD OR, 1.7; 95% CI, 1.3-2.3). Hip BMD/BMAD decreased linearly from age 20 years onward in both genders, while spinal BMD/BMAD declined after age 40 in women but not in men. In both genders, total wrist BMD/BMAD decreased after age 50. By World Health Organization criteria, the age-adjusted prevalence of osteoporosis at the hip, spine, or wrist was 35% among women >/=50 years of age. A similar approach (BMD > 2.5 SD below the young male mean) produced an osteoporosis prevalence rate in men >/=50 years of age of 19%. Thus, bone density predicts fracture risk in men as it does in women, and the prevalence of osteoporosis in men, using sex-specific normal values, is substantial. These observations indicate a need for better prevention and treatment strategies for men.     

Long-term bone marrow culture profiles in patients with myelodysplastic syndromes are not explicable by defective apoptosis

PURPOSE: To compare intraoperative anaesthetic and haemodynamic effects of clonidine-bupivacaine, morphine-bupivacaine and placebo-bupivacaine combinations during continuous spinal anaesthesia. METHODS: Thirty six geriatric patients, undergoing knee replacement using continuous spinal anaesthesia were randomly assigned to: Placebo (n = 12), clonidine (n = 12) and morphine (n = 12), where 1 ml saline, 0.15 mg clonidine or 0.15 mg morphine were mixed with 10 mg bupivacaine 0.5%. Anaesthetic variables studied were maximal sensory level and degree of motor block, duration of surgical analgesia and duration of anaesthesia. Changes in systolic arterial pressure and vasopressor requirements were evaluated. RESULTS: Maximal sensory level and degree of motor block were comparable among the groups. Before surgery two patients in the placebo group, three in the clonidine and one in the morphine group received one additional ml bupivacaine 0.5% because of inadequate anaesthesia and were not considered for determination of duration of surgical analgesia. In the remainder, 1/9 in the clonidine group, 8/10 in placebo and 8/11 in morphine (P < 0.05) received reinjection of bupivacaine for surgical pain. These injections were given about 2 1/2 hr after the initial intrathecal injection, the duration of anaesthesia being about four hours. During the first 30 min after the initial injection the decrease in systolic pressure was greater in the clonidine and morphine than in the placebo group (P < 0.05). Thereafter, vasopressor requirements were higher only in the clonidine group (P < 0.05). CONCLUSION: In elderly patients 0.15 mg clonidine but not 0.15 mg morphine prolonged surgical analgesia when added to 10 mg plain bupivacaine.     

Potassium channels participate in gastric mucosal protection in rats with partial portal vein ligation

Glybenclamide, an adenosine triphosphate-dependent potassium (K+(ATP)) channel blocker, lowered portal pressure and attenuated the hyperdynamic splanchnic circulation in rats with partial portal vein ligation (PPVL). The purpose of this report was to confirm these observations and to test the hypothesis that glybenclamide could reduce acidified ethanol-induced gastric mucosal injury in rats with PPVL. Gastric mucosal blood flow (hydrogen gas clearance), systemic blood pressure, and portal pressure were monitored in rats with PPVL or sham operation (SO). Intravenous glybenclamide (20 mg/kg) or vehicle was administered, followed by intragastric acidified ethanol (0.15 N HCl and 15% ethanol). The area of gastric mucosal lesions was assessed by image analysis. In contrast to published findings, there was no significant elevation of portal pressure after glybenclamide administration in rats with PPVL. Glybenclamide did not alter the gastric mucosal hyperemia in these rats. Glybenclamide significantly increased mucosal injury. The data are consistent with the hypothesis that K+(ATP) channels play a role in protecting the gastric mucosa in rats with PPVL.     

Immunoglobulin levels in populations with low hemoglobin levels: study of five tribes of central India

Average hemoglobin levels for 424 individuals belonging to 5 tribes of central India vary between 10.64 g/dl and 11.30 g/dl among males and between 9.62 g/dl and 9.97 g/dl among females. These ranges indicate the poor state of health and nutrition in these tribes. Three immunoglobulin levels (IgG, IgA, and IgM) measured in a subset of the 424 individuals reveal that immunoglobulin and hemoglobin levels are inversely related to some extent. Levels of all three classes of immunoglobulins were found to be significantly correlated. This suggests that humoral immunity is not impaired even under acute nutritional stress.     

Aminoacylation of hypomodified tRNAGlu in vivo

The highly specific interaction of each aminoacyl-tRNA synthetase and its substrate tRNAs constitutes an intriguing problem in protein-RNA recognition. All tRNAs have the same overall three-dimensional structure in order to fit interchangeably into the translational apparatus. Thus, the recognition by aminoacyl-tRNA synthetase must be more or less limited to discrimination between bases at specific positions within the tRNA. The hypermodified nucleotide 5-methylaminomethyl-2-thiouridine (mnm5s2U) present at the wobble position of bacterial tRNAs specific for glutamic acid, lysine and possibly glutamine has been shown to be important in the recognition of these tRNAs by their synthetases in vitro. Here, we have determined the aminoacylation level in vivo of tRNAGlu, tRNALys, and tRNA1GIn in Escherichia coli strains containing undermodified derivatives of mnm5s2U34. Lack of the 5-methylaminomethyl group did not reduce charging levels for any of the three tRNAs. Lack of the s2U34 modification caused a 40% reduction in the charging level of tRNAGlu. Charging of tRNALys and tRNA1Gln were less affected. There was no compensating regulation of expression of glutamyl-tRNA synthetase because the relative synthesis rate was the same in the wild-type and mutant strains. These results indicate that the mnm5U34 modification is not an important recognition element in vivo for the glutamyl-tRNA synthetase. In contrast, lack of the s2U34 modification reduced the efficiency of charging by at least 40%. This is the minimal estimate because the turn-over rate of Glu-tRNAGlu was also reduced in the absence of the 2-thio group. Lack of either modification did not affect mischarging or mistranslation.     

Bilateral transfer deficit in schizophrenia: a trait marker

To elucidate the relation between the distribution of F-actin bands in the clear zone and the bone-resorbing activity of osteoclasts in vivo, the endocranial surfaces of calvariae from 7-day-old Wistar rats were stained with F-actin-specific fluorescein isothiocyanate-labeled phalloidin (FITC-phalloidin) with and without the intraperitoneal injection of the calcium-regulating hormones, calcitonin (CT), and parathyroid hormone (PTH). Some specimens were double-stained with FITC-phalloidin and a monoclonal antibody, ED1, which stained monocytes and macrophages. In normal rats, almost 80% of the osteoclasts showed ring-shaped F-actin bands in the clear zone, and the remaining 20% showed arch- or line-shaped F-actin bands. From 15 min to 1 h after the injection of CT (salmon, 10 mg/kg), the number of osteoclasts with ring-shaped F-actin bands decreased significantly. At 1 h, few F-actin bands were detected in osteoclasts, which were still stained by ED1. However, these F-actin bands recovered to the normal level at 6 h. On the other hand, from 15 min to 6 h after the injection of PTH (bovine, 50 mg/kg), the number of osteoclasts with arch- or line-shaped F-actin bands decreased significantly. These results indicate that osteoclasts with arch- or line-shaped F-actin bands in the clear zone had lower bone-resorbing activity than those with ring-shaped F-actin bands, and that the formation of bands could be controlled by calcium-regulating hormones over the course of a few hours. Observation of the endocranial surfaces of calvariae might be useful for examining factors which affect the activities of osteoclasts in vivo.