Citation for the 1998 Gerald D. Aurbach Lecture Award of the Endocrine Society to Dr. JoAnne S. Richards

Rectal stenosis following low anterior resection is common. Several methods of treatment have been described. We introduce a simple method for the treatment of anastomotic stenosis using a conventional proctoscope and an electric knife with a Foley catheter as an anvil. Under direct vision, this technique can afford accurate and safe incision of stenosis.     

Purine-rich enhancers function in the AT-AC pre-mRNA splicing pathway and do so independently of intact U1 snRNP

A rare class of introns in higher eukaryotes is processed by the recently discovered AT-AC spliceosome. AT-AC introns are processed inefficiently in vitro, but the reaction is stimulated by exon-definition interactions involving binding of U1 snRNP to the 5' splice site of the downstream conventional intron. We report that purine-rich exonic splicing enhancers also strongly stimulate sodium channel AT-AC splicing. Intact U2, U4, or U6 snRNAs are not required for enhancer function or for exon definition. Enhancer function is independent of U1 snRNP, showing that splicing stimulation by a downstream 5' splice site and by an exonic enhancer differ mechanistically.     

Enhanced Th2-like responses in IL-1 type 1 receptor-deficient mice

IL-1 has a number of effects on T cell growth but a specific role for IL-1 in T cell responses in vivo has not been elucidated. In this study the role of IL-1 in Th1/Th2 responses was examined in mice deficient for the IL-1 type 1 receptor (IL-1RI-/-) during cutaneous Leishmania major infection or following immunization with keyhole limpet hemocyanin (KLH). After inoculation of L. major stationary phase promastigotes into the hind footpad, both IL-1RI-/- and wild-type (WT) mice developed small lesions which resolved spontaneously. Lymph node cells from infected IL-1RI-/- mice produced significantly more IL-4 and IL-10 than those from WT mice following antigenic stimulation in vitro. Splenocytes from IL-1RI-/- and WT mice showed similar levels of antigen-induced proliferation. In contrast, splenocyte cultures from the IL-1RI-/- mice contained significantly more IL-4 than those from WT mice. Similar results were also obtained after immunization with KLH. While lymph node cells from both IL-1RI-/- and WT mice displayed similar levels of KLH-specific proliferation, those from IL-1RI-/- mice produced significantly more IL-4 than those from WT mice. Conversely, antigen-stimulated lymph node cells from WT mice secreted significantly greater amounts of IFN-gamma as compared with those from IL-1RI-/- mice. These data indicate that while IL-1 is not required for mounting an immune response or antigen-dependent proliferation, it appears to be required for normal regulation of Th1/Th2 responses and may function to negatively regulate IL-4 expression.     

Novel carbocyclic nucleosides containing a cyclobutyl ring. Guanosine and adenosine analogues

(1R,cis)-2-(3-Amino-2,2-dimethylcyclobutyl)ethanol (4) was used as a precursor in the synthesis of cyclobutyl nucleoside analogues containing guanine, 8-azaguanine, adenine or 8-azaadenine. All the compounds were evaluated as antiviral agents in a variety of assay systems. Some activity was noted for compound 13, 17, 19 and 20 against vaccinia virus and for compounds 11, 12, 13, 17, 19 and 20 against herpes simplex virus, at concentrations that were up to 10-fold below the cytotoxic concentrations for the host cells.     

Laparoscopic colorectal surgery. The first experiences from the Central Hospital of Akershus

Between November 1993 and August 1997, 49 patients (29 women and 20 men) were selected to 51 laparoscopic and laparoscopic-assisted colonic or rectal operations. Five operations were converted to open surgery because of technical problems and adhesions. 46 operations could be performed as planned. The median age was 67 years (20-88 years). A variety of procedures were carried out, including construction of deviating sigmoideostomas without resection (n = 17), segmental resections of colon (n = 15), rectopexi (n = 6), stoma closure (n = 4), abdominoperineal resection (n = 3) and suture of an iatrogenic perforation of the large bowel (n = 1). Eight of the patients with a bowel resection had carcinoma. The median duration of the procedures was 112 minutes (38-293 minutes) and the length of hospitalisation eight days (2-40 days). 13 patients (28%) developed complications. One of these patients died and four were reoperated. These first experiences show that we are able to perform a variety of colorectal surgery laparoscopically. An experienced, well organised operating team with modern laparoscopic equipment is essential to this type of surgery. Prospective, randomised studies have to be done to assess the efficacy of the laparoscopic approach.     

Neurologic manifestations of HIV infection. Using imaging studies and antiviral therapy effectively

Patients with HIV infection are at risk for neurologic complications that can arise through various means. Nervous system disorders sometimes occur as a direct consequence of the HIV infection itself. Or, as immunodeficiency progresses, patients can become susceptible to numerous opportunistic infections and other conditions that have neurologic involvement. Even the antiviral drugs used to treat HIV infection can induce neurologic manifestations. Dr Rachlis discusses several of these manifestations and their management.     

Urethroplasty for balanitis xerotica obliterans

PURPOSE: To report a 20-month-old child with a rapidly growing dome-shaped red nodule on the left lower eyelid. The lesion was diagnosed clinically as an hemangioma, but microscopy disclosed an epithelioid Spitz nevus. METHOD: Case report. RESULT: Histopathologic examination of the excised lesion disclosed a Spitz nevus (benign juvenile melanoma) of a chiefly epithelioid cell type. CONCLUSIONS: The differential diagnosis of eyelid skin nodules in children should include Spitz nevus. This uncommon nevus has many cytologic features in common with nodular malignant melanoma. Histologically, it may be difficult to distinguish between nodular malignant melanoma and Spitz nevus.     

Antimycobacterial activity of substituted isosteres of pyridine- and pyrazinecarboxylic acids

Pyrazines and pyridines substituted with alkylated tetrazoles, esterified vinylogous carboxylic acids, and ketosulfides were synthesized as precursors of antimycobacterial agents which, after penetration of the mycobacterial cell wall, could be biotransformed by esterases or peroxidase-catalases. The expected products are tetrazoles, a vinylogous carboxylic acid, and CH-acidic ketosulfoxides, isosteres of pyrazinoic and nicotinic acids, which should inhibit mycobacterial growth when released inside the bacterial cell. The growth inhibitory activity of the synthesized compounds against the H37Rv strain of Mycobacterium tuberculosis was determined to assess the viability of this concept. It was shown that all of the compounds designed as lipophilic precursors were more active than the unmodified polar isosteres of pyrazinoic and nicotinic acids.     

Distributed accessibility control points help deliver a directly accessible Web

This paper describes a set of interfaces and mechanisms to enhance access to the World Wide Web for persons with sensory, cognitive, or motor limitations. Paradoxically, although complex Web architectures are often accused of impeding accessibility, their layers expand the range of points where interventions can be staged to improve it. This paper identifies some of these access control points and evaluates the particular strengths and weaknesses of each. In particular, it describes an approach to enhance access that is distributed across multiple control points and implemented as an aggregation of services. Published online: 6 November 2002     

Inhibition of ornithine decarboxylase potentiates nitric oxide production in LPS-activated J774 cells

We have examined whether modulation of the polyamine biosynthetic pathway, through inhibition by alpha-difluoromethylornithine (DFMO) of the rate limiting enzyme, ornithine decarboxylase (ODC), modulates NO synthesis in J774 macrophages. DFMO potentiated LPS-stimulated nitrite production in both a concentration- and time-dependent manner, increasing nitrite levels by 48+/-5% at 10 mM. This effect was observed in cells pre-treated with DFMO for 24 h prior to stimulation with LPS. Addition of DFMO 12 h after LPS failed to potentiate LPS-induced nitrite production. Supplementation of the culture medium with horse serum (10%) in place of foetal calf serum (10%) caused no significant change in either LPS-induced nitrite production or in the ability of DFMO (10 mM) to potentiate LPS-induced NO synthesis. Metabolism of L-[3H]arginine to L-[3H]citrulline by partially purified inducible nitric oxide synthase (iNOS) was not significantly altered by either DFMO (1-10 mM) or by putrescine (0.001-1 mM), spermidine (0.001-1 mM) or spermine (0.001-1 mM). iNOS activity was also unaffected by 1 mM EGTA but was markedly attenuated (70+/-0.07%) by L-NMMA (100 microM). Pre-incubation of cells with DFMO (10 mM; 24 h) prior to activation with LPS resulted in enhanced (approximately 2 fold) iNOS protein expression. These results show that DFMO potentiates LPS-induced nitrite production in the murine macrophage cell line J774. Since the only known mechanism of action of DFMO is inhibition of ODC, and thus polyamine biosynthesis, we conclude that expression of iNOS can be critically regulated by endogenous polyamines.