Assignment of Ptprn2, the gene encoding receptor-type protein tyrosine phosphatase IA-2beta, a major autoantigen in insulin-dependent diabetes mellitus, to mouse chromosome region 12F

Synapses obtained in vitro in a system of co-culture of muscle cells and neurons are of embryonic type. We prepared a monoclonal antibody (6.17) which recognizes a molecule synthesized by Schwann cells and used it to show that the main characteristics of maturity (decrease in number of synapses, appearance of junctional folds, and suppression of butyrylcholinesterase expression) are under the control of Schwann cells. In addition, Schwann cells have the capacity to aggregate the acetylcholine receptors in myotube cultures.     

A prospective randomized trial of Teflon versus polyethylene stents for distal malignant biliary obstruction

BACKGROUND AND STUDY AIMS: Clogging of biliary stents continues to be a major clinical problem. Different polymer materials may have different effects on clogging. In vitro studies have shown a direct relation between the frictional coefficient of a polymer and the amount of encrusted material. Teflon appeared to be the best polymer for biliary stents. Two different types of stents made of Teflon have been tested in clinical practice and showed favourable patency rates. However, a randomized trial has never been performed. We compared the patency of an Amsterdam-type polyethylene stent with a Teflon stent in a prospective randomized trial. PATIENTS AND METHODS: Between September 1995 and November 1996, 42 patients received a Teflon stent and 42 patients a polyethylene stent. All patients had a distal malignant biliary stricture without a previous drainage procedure. Diagnoses included carcinoma of the pancreas (n = 76), papilla (n = 1), bile duct (n = 5) and metastases (n = 2). The internal and external diameter (10 Fr), length (9 cm) and stent design (a straight stent with two side flaps and one side hole at each end) were similar for both stents. RESULTS: A reduction in bilirubin of more than 20% within one week was seen in 91% of the patients. Early complication rates were similar in both groups (10%). The median follow-up was 142 days. Stent dysfunction occurred in 28 Teflon and 29 polyethylene stents. The thirty-day mortality was 14% in both groups. Patient survival did not differ significantly between the groups (median survival: Teflon 165 days, polyethylene 140 days). The median stent patency was 83 days for Teflon and 80 days for polyethylene stents, and was not significantly different either. CONCLUSION: Teflon material did not improve patency in biliary stents with an Amsterdam-type design.     

Cloning and characterization of Schistosoma mansoni fructose-1,6-bisphosphate aldolase isoenzyme

A Schistosoma mansoni cercarial cDNA expression library, constructed in lambda gt11, was screened using the IgG fraction of sera taken from rabbits vaccinated with irradiated cercariae. A positive cDNA clone (1,431 base pairs) was selected and characterized. The amino acid sequence predicted from the cDNA sequence identified a polypeptide of 363 amino acids that showed significant homology to different family members of the enzyme fructose-1,6-bisphosphate aldolase (EC 1.4.2.13). The identity was 66% and 65% with human C and A isoenzymes, respectively. Active sites and substrate-binding determinant analysis suggest that the isolated enzyme in terms of function resembles type A aldolase. The recombinant protein expressed in the vector pGEX-2T was found to be active enzymatically. Antibodies raised against the purified recombinant protein recognized a 40-kDa band in extracts from cercariae, schistosomula (5 and 25 days), adult worms, and eggs. Using immunocytochemistry, aldolase localized to the tegumental region of the adult worms.     

Identification of nitric oxide synthases in isolated bovine brain vessels

Initial reports on antiproteinuric effect of pefloxacine in small groups of patients with minimal-change nephropathy (MCN) and focal and segmental glomerulosclerosis (FSGS) have not been confirmed in other papers. To assess its antiproteinuric effect in experimental animals we administered pefloxacine to rats with adriamycin nephropathy showing morphological changes resembling human minimal-change disease or focal segmental glomerulosclerosis, and clinically with full-blown nephrotic syndrome. Pefloxacine treatment was at least partially effective in preventing further increase of proteinuria in rats with adriamycin nephropathy. The mechanism of this effect remains unclear and deserves further studies concentrating on the glomerular cytokine network and glomerular production of reactive oxygen species.     

Rasmussen syndrome

INTRODUCTION: Rasmussen's encephalitis is a neurological disorder probably of immunological origin, characterized by intractable epilepsy, neurological deterioration and the presence of antibodies against R3 glutamate receptors. OBJECTIVE: To present the experience of an Argentinian Paediatric Neurology Service during the past 7 years. MATERIAL AND METHODS: We analyzed the clinical histories of 12 patients with RS as defined by the diagnostic criteria proposed by Hart et al. We evaluated the following parameters: neurological examination, neuropsychological assessment, types of crises, age of onset, frequency, distribution, electroencephalogram, video EEG, evoked potentials, neuro-radiological studies; CT and cerebral MR using gadolinium, SPECT, lumbar puncture and cerebral biopsy. RESULTS: The crises were of simple partial motor type in 12 cases, secondarily generalized partial crises in 7 cases, complex partial crises in 4 cases and partial and generalized motor states in 8 cases. RESULTS. The ictal EEGs during the continuous partial crises showed contralateral focal slow activity of the affected side of the body in 30% of cases. The neuro-radiological studies (CT and MR) showed signs of cerebral hemiatrophy in all 12 cases, hyper-intense images in the T2 sequences of the fronto-temporo-parietal regions in 5 cases, an asymmetric megacisterna magna in 1 case and hypoplasia of the cerebellar vermis in another case. CONCLUSIONS: The continuous partial crises showed little correlation with the electro-encephalography. Following administration of i.v. gammaglobulin there was a transient halt in progression of the neurological deterioration and control of the crises in 55% of the cases. Surgery continued to be the treatment recommended for control of the epileptic crises.     

Posttreatment with eicosatetraynoic acid decreases lung edema in guinea pigs exposed to phosgene: the role of leukotrienes

Acetylenic acids such as 5,8,11,14-eicosatetraynoic acid (ETYA), have been shown to be effective in preventing pulmonary edema formation (PEF). In phosgene-exposed guinea pigs, we examined the effects of ETYA on PEF, measured as real time lung weight gain (lwg). Pulmonary artery pressure (Ppa), airway pressure (Paw), perfusate leukotrienes (LT) C4/D4/E4/B4, and lung tissue lipid peroxidation (TBARS) were measured using the isolated, buffer-perfused lung model. Guinea pigs were challenged to 175 mg/m3 (44 ppm) phosgene for 10 minutes giving a concentration x time product of 1750 mg.min/m3 (437 ppm.min). Five minutes after removal from the exposure chamber, guinea pigs were treated, i.p., with 200 microL of 100 microM ETYA. 200 microL of 50 microM ETYA was added to the perfusate every 40 minutes, beginning at 60 minutes after start of exposure (t = 0). There were four groups in this study: air-treated, phosgene-exposed, ETYA-posttreated + phosgene, and ETYA-posttreated + air ETYA-posttreated + phosgene guinea pigs had significantly lower Ppa (P = .006), Paw (P = .009), and lwg (P = .016) compared with phosgene-exposed animals. Phosgene exposure reduced LTB4 compared with air-treated controls (P = .09). ETYA-posttreatment + phosgene had significantly increased perfusate LTB4 (P = .0006) compared with phosgene exposure only group. Total perfusate, LTC4 + LTD4 + LTE4, was not different between phosgene-exposed, air-treated or ETYA-posttreatment + phosgene over time. Posttreatment with ETYA significantly lowered TBARS formation, 206 +/- 13 versus 285 +/- 23 nmol/mg protein (P = .016), compared with phosgene-exposed lungs. Paradoxically, ETYA posttreatment decreased PEF and lipid peroxidation, but increased sulfidopeptide LT release from the lung during perfusion. We conclude that LTC4/D4/E4, and B4, may play different roles than previously thought for PEF in the isolated perfused lung model.     

Synthesis and in vitro activity of some epimeric 20 alpha-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase and 5 alpha-reductase

Some epimeric 20-hydroxy, 20-oxime, 16 alpha, 17 alpha-, 17,20- and 20,21-aziridine derivatives of progesterone were synthesized and evaluated as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase (P450(17) alpha) and 5 alpha-reductase (5 alpha-R). The reduction of 16-dehydropregenolone acetate (3a) was reinvestigated. NaBH4 in the presence of CeCl3 gave better stereo-selectivity for 20 beta-ol [20 alpha/20 beta-OH (4 alpha/4 beta) = 1/2.7] than LTBAH or the Meerwein-Pondroff method reported; reduction with Zn in HOAc formed exclusively 20 alpha-ol (4 alpha b). The 20 alpha- and 20 beta-hydroxy-4,16-pregnadien-3-one (9 alpha) and (9 beta) were synthesized from the alcohols 4 alpha b and 4 beta b. Several 20-oxime pregnadienes and 16 alpha, 17 alpha-, 17,20- and 20,21-aziridinyl-5-pregnene derivatives were also synthesized. LiAlH4 reduction of the 16-en-20-oxime (12b) yielded 20 (R)-(13a) and 20(S)-17 alpha,20-aziridine (13b) and 20(R)-17 beta,20-aziridine (14a). Several compounds inhibited the human P450(17) alpha with greater potency than ketoconzole. The 5 alpha-R enzyme assay showed that while (9 alpha) did not have any activity, (9 beta) and (3b) were potent 5 alpha-reductase (IC50 = 21 and 31 nM) inhibitors with activities similar to finasteride. The 20-oximes (17a) and (17b) were potent dual inhibitors for both 5 alpha-R (IC50 = 63 and 115 nM, compared to 33 nM for finasteride) and P450(17) alpha (IC50 = 43 and 25 nM, compared to 78 nM for ketoconazole).     

Australian and South African undergraduates' HIV-related knowledge, attitudes, and behaviors

To understand safe sex behavior in two countries which have been differentially affected by the HIV/AIDS epidemic, the present study compared the AIDS-related knowledge, attitudes, and behaviors of 920 heterosexual undergraduate students in Australia and 228 heterosexual undergraduate students in South Africa. South African students were found to have significantly less knowledge about HIV/AIDS, and significantly less favorable attitudes toward safe sex behavior than their Australian counterparts. They were also more likely to report that they have avoided various groups of people for fear of contracting AIDS. Experience from Australia over the period 1986-1995 suggests that significant improvements in the AIDS-related knowledge, attitudes, and behaviors of South African undergraduates are achievable.     

In utero transplantation of human fetal haemopoietic cells in NOD/SCID mice

BACKGROUND: Carotid angioplasty (CA) has been suggested to be a safer and more cost-effective alternative to carotid endarterectomy (CEA) in the management of symptomatic severe internal carotid artery (ICA) disease. METHODS: The study was conducted as a prospective consecutive randomized trial of CEA versus CA for symptomatic severe ICA disease in a university teaching hospital. All patients were assessed before and after surgery by a neurologist. The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis (> 70%) who were randomized to either CEA or CA. However, only 17 had received their allocated treatment before trial suspension. CEA with patching or CA with stenting were used as interventions. The main outcome measures were death or disabling or nondisabling stroke within 30 days. RESULTS: All 10 CEA operations proceeded without complication, but 5 of the 7 patients who underwent CA had a stroke (P=.0034), 3 of which were disabling at 30 days. CONCLUSIONS: After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted--even in an amended format-primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.