Foot deformities in rheumatoid arthritis patients and their effects on foot functions.

OBJECTIVE: Foot problems are common clinical disorders in patients with Rheumatoid Arthritis (RA). The aim of this study was to investigate the frequency and impact of foot and ankle problems in patients with RA. PATIENTS AND METHODS: A total of 164 feet of 82 RA patients with a diagnosis of one year or more were evaluated. Deformities including HV, CT, SF, PC, PP, MPS, MPV, and HT were examined in all RA patients. The Foot Function Index was used to measure the impact of these deformities on pain, disability, and movement limitations. Radiological changes were measured using the modified Larsen score. RESULTS: The frequency of deformity in RA patients was found to be 95.1%, with HV deformity being the most common at 84.1%. There was a statistically significant relationship between SF, HV, PP, and PC deformities and disease duration. In our sample of 82 patients, 70 (85.3%) reported past or present foot pain complaints. The most common site of pain was the ankle joint, with 44 (53.7%) patients experiencing ankle pain. A statistically significant increase in the frequency of ankle pain was found as DAS28 scores, body mass index (BMI), and disease duration increased. There was also a correlation between an increase in DAS28 scores and the frequency of forefoot pain. A significant correlation was found between MPV, HV, PP, and PC deformities and high FFI scores. Larsen radiological scores were not correlated with foot-ankle pain or duration of pain. CONCLUSIONS: These findings suggest that foot deformities are common in RA, and it is important to address them early in the disease course to minimize functional disability and improve quality of life.

Regulation of human natural killer (NK) cell function: induction of killing of an NK-resistant renal carcinoma cell line.

Natural killer (NK)-like activity against a renal carcinoma cell line, Cur, was assessed. There was no spontaneous killing of Cur cells by human peripheral blood mononuclear cells in 4-hr assays. Cur killing was observed in 18-hr assays, but the magnitude of killing was variable and always markedly less than that against K562. Cur killing was mediated by a nonadherent, nonphagocytic lymphocyte, the activity of which could be modulated both positively and negatively by monocytes or their products. Preincubation of effectors with monocyte supernatant, interleukin 1 (IL-1), alpha-interferon (alpha IFN), or interleukin 2 (IL-2) greatly increased the magnitude of Cur killing and accelerated the kinetics of lysis. The addition of prostaglandin E2 (PGE2) during in vitro activation of NK by IL-2 profoundly inhibited subsequent Cur lysis, whereas only minimal inhibition of K562 lysis was noted. However, following activation with IL-2, lysis of Cur targets was less sensitive to the inhibitory effects of PGE2. Removal of Leu 11b(+), OKM1(+), or L-leucyl-leucine methyl ester-sensitive cells markedly decreased both Cur and K562 lysis. Moreover, CD16(+) cells purified with the fluorescence-activated cell sorter were found to mediate Cur killing. Whereas Cur and K562 lysis is mediated by phenotypically similar effector cells, the present studies demonstrate that the cytotoxic functions defined by the ability to lyse these two targets differ in response to a variety of immunoregulatory stimuli.

Effect of dimethyldioctadecylammonium bromide induced macrophages on malignant cell proliferation.

Murine peritoneal macrophages elicited by dimethyldioctadecylammonium bromide (DDA), which is a potent immunologic adjuvant, were examined for cytotoxic and growth inhibiting activity for malignant cells. DDA macrophages had no cytolytic activity for murine B16BL-6 melanoma or human SMS-SB pre-B leukemia cells even in the presence of up to 1 microgram bacterial endotoxin (lipopolysaccharide, LPS)/ml. However, they exhibited a variable inhibitory effect on the growth of several lines of leukemia cells. The number of SMS-SB and human NALL cells remained essentially static in the presence of DDA macrophages while they increased significantly when cultured with resident macrophages. In contrast, L1210 cells increased 5-8-fold in the presence of macrophages elicited either by DDA or the inflammatory agent proteose peptone (PP). Although DDA macrophages retarded L1210 growth relative to PP macrophages, both populations responded to LPS in a comparable dose dependent manner to become essentially cytostatic at 1 microgram LPS/ml.

Effect of dimethylsulfoxide and butyrate on 5'-nucleotidase of human renal carcinoma cells.

The effect of dimethylsulfoxide (DMSO) and butyrate, agents which induce differentiation of certain cancer cells, on membrane associated 5'-nucleotidase (5'-NT) of 2 human renal carcinoma cell lines (Cur and Caki) was investigated. Under a variety of conditions of agent addition, 5'-NT specific activity increased in Cur and decreased in Caki cells. This opposite response pattern was observed for assays performed on lysates at pH 9.0 and 7.4 and assays with intact cell monolayers, even under conditions of identical cellular growth inhibition. It is concluded that the cell lines responded in a fundamentally different way to the chemical agents. An increase in 5'-NT has correlated with cell maturation for a number of processes. The DMSO induced increase in Cur 5'-NT was dependent on protein synthesis.

Naturally occurring cell-mediated cytotoxicity against simian virus 40-transformed 3T3 murine tumor cells.

The tumorigenicity and host protective mechanisms induced by simian virus 40 (SV40)-transformed 3T3 cells (SV403T3) were evaluated in syngeneic BALB/c mice. Tumors were regularly produced by sc inoculation of SV403T3 cells; the incidence, latent period, and survival were proportional to the size of the initial inoculum. With the use of an in vitro 18-hour 51Cr cytotoxicity assay, spleen cells from normal mice showed a dose-related killing activity against the SV403T3 cells. At an effector cell-to-target cell ratio of 200:1, the average lysis was 56 +/- 6%. This reaction appeared specific for the virally transformed targets; the mean lysis of parent 3T3 cells was 23 +/- 5%. Effectors were resistant to anti-theta serum and not removed by adherence to plastic or nylon wool. Tissue distribution studies indicated that these effectors were present in high concentrations in spleen, bone marrow, lymph nodes, and peritoneal cavity. Low levels of activity were associated with cells from the thymus. In the present studies specific T-cell cytotoxicity against the SV403T3 cells could not be demonstrated. Animals challenged with nonviable SV403T3 cells prior to tumor cell inoculation did not show increased in vivo resistance. In parallel, the in vitro cytotoxicity of animals inoculated with SV403T3 tumor cells showed no heightened cell killing compared to the cytotoxicity of normal controls.