Cytokine production from colonic T cells in patients with ulcerative colitis with and without primary sclerosing cholangitis

PURPOSE: Only five percent of all patients with ulcerative colitis develop primary sclerosing cholangitis. T cells accumulate at the sites of the colonic and bile duct inflammation in both ulcerative colitis and primary sclerosing cholangitis. T helper cell populations comprise functionally distinct subsets characterized by the cytokines they produce. Several alterations in cytokine production have been described in patients with ulcerative colitis. The aim of this study was to investigate possible differences in T helper subsets and cytokine production in peripheral blood and colonic mucosa among ulcerative colitis patients with and without primary sclerosing cholangitis. METHODS: Eleven patients with primary sclerosing cholangitis and extensive ulcerative colitis, 11 patients with extensive ulcerative colitis and no liver disease, and 5 patients without any history of liver disease who underwent routine colonoscopy because of previous polypectomy were included in the study. Colonoscopy with multiple biopsies was performed on all patients. Lamina propria mononuclear cells and peripheral blood mononuclear cells were isolated. A modified version of solid-phase enzyme-linked immunospot assay was used for the separate counting of cells producing interferon-gamma, interleukin-2 (T helper 1), and interleukin-4 (T helper 2). RESULTS: No differences in spontaneous production of cytokines from peripheral blood mononuclear cells was found among the three groups. Patients with primary sclerosing cholangitis compared with patients with ulcerative colitis without liver disease showed a significant increase in the number of cells secreting interferon-gamma after purified protein derivative stimulation (P < 0.02). More cells secreting interferon-gamma were found in the two ulcerative colitis groups than in the cell populations from healthy controls (P < 0.03). The number of cells secreting interferon-gamma in the primary sclerosing cholangitis group was significantly lower than in the ulcerative colitis group without liver disease (P < 0.04). The number of cells secreting interleukin-4 was lower in the primary sclerosing cholangitis group than among the patients with ulcerative colitis only (P = 0.05). CONCLUSION: Isolated lymphocytes from colonic mucosa differ in cytokine production in patients with ulcerative colitis with and without primary sclerosing cholangitis.     

A design rationale for a language-based editor

This paper reviews the design issues that arise in the construction of effective language-based editors for the preparation of syntactically and static semantically correct language sentences, typically computer programs. The need for such editors to support a pluralistic view of program structure is identified, together with the need to observe the constraints on performance and storage consumption if such editors are to be accepted by professional programmers. From these basic needs, more specific requirements for the display, parsing and semantic checking components of such an editor are derived.     

Multiple mechanisms may affect birth sex ratio in domestic pigs

No abstract. Copyright 1998 The Association for the Study of Animal Behaviour.     

The diffusion of indium in lead films containing gold

Some results on the lateral diffusion of indium in thin lead films containing 2.5 wt.% Au are described. At room temperature the diffusion rate is high with a diffusion coefficient D of about 2.5 x 10^-12 cm² s^-1 and an activation energy of 0.26±0.1 eV. The indium concentration profile along the films is highly irregular and is characterized by a sharp peak within the diffused film area at the diffusion front. Some of the irregularities are explained by the formation of filaments of near-stoichiometric AuIn₂ and by diffusion around grains of varying size. The preferential formation of AuIn₂ is likely to be the cause of the lower diffusion rate observed in the Pb-Au films in comparison with pure lead films. It is found that hillocks are nucleated in the vicinity of the indium diffusion front, indicative of strain relaxation.     

Some aspects of the static and dynamic compressive behaviour of β-brass single crystals

The compressive behaviour of β-brass single crystals has been investigated in uninterrupted static and dynamic tests and in interrupted tests using static-static, static-dynamic, dynamic-dynamic and dynamic-static loading sequences. Static and dynamic strain-rates were 1.5×10^?4 and 3.2×10³ sec^?1 respectively. Slip traces on the statically deformed crystals were wavy and deformation occurred by single slip on either (ī01) [111] or (¯211) [111] or by a transition mode involving both (ī01) [111] and (¯211 [111]. Except for anomalous behaviour in the dynamic reload following static preload the dynamic slip traces were straight with deformation occurring by multiple slip on four {110} planes involving two 〈111〉 directions. It is shown that there is no direct causal relationship between the lower work-hardening rate and level of flow stress and the crystallography of slip in dynamic deformation. The work-hardening rate and flow stress in static and dynamic loading are rather determined by the dynamics of the deformation. The differences in the substructural features as observed by transmission electron microscopy arise principally from the differences in the slip modes and cannot be interpreted as controlling the stress-strain behaviour. The low work-hardening rate and flow stress in dynamic deformation is believed to be due to the production of short-lived disorder. The absence of a/2〈111〉 dislocations in thin foils is explained in terms of the fast reordering reaction in β-brass.     

Telescoping Languages: A Strategy for Automatic Generation of Scientific Problem-Solving Systems from Annotated Libraries

As machines and programs have become more complex, the process of programming applications that can exploit the power of high-performance systems has become more difficult and correspondingly more labor-intensive. This has substantially widened the software gap—the discrepancy between the need for new software and the aggregate capacity of the workforce to produce it. This problem has been compounded by the slow growth of programming productivity, especially for high-performance programs, over the past two decades. One way to bridge this gap is to make it possible for end users to develop programs in high-level domain-specific programming systems. In the past, a major impediment to the acceptance of such systems has been the poor performance of the resulting applications. To address this problem, we are developing a new compiler-based infrastructure, called TeleGen, that will make it practical to construct efficient domain-specific high-level languages from annotated component libraries. We call these languages telescoping languages, because they can be nested within one another. For programs written in telescoping languages, high performance and reasonable compilation times can be achieved by exhaustively analyzing the component libraries in advance to produce a language processor that recognizes and optimizes library operations as primitives in the language. The key to making this strategy practical is to keep compile times low by generating a custom compiler with extensive built-in knowledge of the underlying libraries. The goal is to achieve compile times that are linearly proportional to the size of the program presented by the user, rather than to the aggregate size of that program plus the base libraries.     

The importance of physicochemical swelling in cartilage illustrated with a model hydrogel system

The physicochemically derived swelling stress in articular cartilage plays a crucial role in determining the pattern of stress sharing between the exudable fluid and the 'solid' components comprising its matrix. This pattern of stress sharing in turn influences the manner in which cartilage consolidates or deforms in compression via the outflow of fluid. Synthetic hydrogels exposed to a variety of cationic blocking solutions provide simplified model systems for exploring quantitatively the influence of the intrinsic swelling parameter on consolidation behaviour, thus yielding further insights into the fundamental parameters controlling the biomechanical properties of complex tissues such as articular cartilage.     

Nonclassical 2,4-diamino-8-deazafolate analogues as inhibitors of dihydrofolate reductases from rat liver, Pneumocystis carinii, and Toxoplasma gondii

The synthesis and biological activity of 42 6-substituted-2,4-diaminopyrido[3,2-d]pyrimidines (2,4-diamino-8-deazafolate analogues) are reported. The compounds were synthesized in improved yields compared to previous classical analogues using modifications of procedures reported previously by us. Specifically, the S-phenyl-; mono-, di-, and trimethoxyphenyl-; and mono-, di-, and trichlorophenyl-substituted analogues with H or CH3 at the N10 position and methyl and trifluoromethyl phenyl ketone analogues with H, CH3, and CH2C identical to CH at the N10 position were synthesized. The S10 and N10 alpha- and beta-naphthyl analogues along with the N10 CH3 analogues were also synthesized. These compounds were evaluated as inhibitors of dihydrofolate reductases (DHFR) from Pneumocystis carinii (pc) and Toxoplasma gondii (tg); selectivity ratios were determined against rat liver (rl) DHFR as the mammalian reference enzyme. Against pcDHFR the IC50 values ranged from 0.038 x 10-6 M for 2,4-diamino-6-[(N-methyl-2'-naphthylamino)methyl]pyrido[3,2-d]pyrimidine (28) to 5.5 x 10(-6) M for 2,4-diamino-6[(2',4'-dimethoxyanilino)methyl]pyrido[3,2-d]pyrim idi ne (15). N10 methylation in all instances increased potency. None of the analogues were selective for pcDHFR. Against tgDHFR the most potent analogue was 2,4-diamino-6-[(N-methylanilino)methyl]pyrido[3,2-d]pyrimidine (5) (IC50 0.0084 x 10(-6) M) and the least potent was 2,4-diamino-6[(2'-naphthylamino)methyl]-pyrido[3,2-d]pyrimidine (37) (IC50 0.16 x 10-6 M). N10 methylation afforded an increase in potency up to 10-fold. In contrast to pcDHFR, several of the 8-deaza analogues were significantly selective for tgDHFR, most notably 2,4-diamino-6-[(2'-chloro-N-methylanilino)-methyl]pyrido[3,2-d] pyrimidine (13), 2,4-diamino-6-[(3',4',5'-trimethoxyanilino)methyl]pyrido[3,2-d]pyr pyrimidine (29), and 2,4-diamino-6-[(2',4',6'-trichloroanilino)methyl]pyrido[3,2-d] pyrimidine (32) which combined high potency at 10-8 M along with selectivities of 8.0, 5.0, and 12.4, respectively. The potency of these three analogues are comparable to the clinically used agent trimetrexate while their selectivities for tgDHFR are 17-43-fold better than trimetrexate.     

Short communication: Effects of analgesic use postcalving on cow welfare and production

The aim of this study was to assess the welfare and production of cows given an analgesic drug (carprofen, 1.4 mg/kg i.v.) within 6 h after calving. The study was performed in a dairy farm with approximately 1,000 milking cows. Behavior, clinical indices, and production data (milk yield and fertility) of cows treated with carprofen (n = 19) or a placebo (n = 20) were compared. Additionally, differences related to parity (primiparous vs. multiparous) were analyzed. No significant differences were observed in the time of placental expulsion or incidence of clinical disease over the 3 d postpartum, but more animals from the analgesia group were observed eating during the first hours after calving.For unassisted calvings, the rectal temperature 24 h postpartum was lower in the cows given analgesic. Total lactation yields at 305 d in milk were higher in the primiparous cows treated with carprofen. Fewer cows were pregnant at 220 d postpartum in the treated group as the use of carprofen increased the time from calving to conception. This study suggests that pain management after parturition leads to earlier feed intake after calving and that this may lead to higher milk yield in first-lactation animals.