Correction to: Measuring treatment effect on psoriatic arthritis-related domains: insights from the SPIRIT-H2H study at weeks 24 and 52

Clinical Rheumatology -     

Correction to: Disease burden and treatment sequence of polymyositis and dermatomyositis patients in Japan: a real-world evidence study

Clinical Rheumatology -     

Simultaneous bilateral fungal keratitis caused by different fungi

Fungal keratitis is an important cause of corneal disease in the tropical world. We report a rare presentation of simultaneous bilateral corneal ulceration caused by different fungi.     

Focal cerebral ischemia upregulates SHP-1 in reactive astrocytes in juvenile mice

The role of the tyrosine phosphatase SHP-1 in the hematopoietic system has been well studied; however, its role in the central nervous system (CNS) response to injury is not well understood. Previous studies in our laboratory have demonstrated increased immunoreactivity for SHP-1 in a subset of reactive astrocytes that do not appear to enter the cell cycle following deafferentation of the chicken auditory brainstem. In order to determine whether mammalian astrocytes also upregulate SHP-1 immunoreactivity following CNS injury, a mouse model of focal cerebral ischemia was utilized to study SHP-1 expression. The brains of 3-week-old mice were analyzed at four time points following permanent middle cerebral artery occlusion (MCAO): 1, 3, 7, and 14 days. Our results demonstrate consistent infarct volumes within surgical groups, and infarct volumes decrease as a function of time from 1 day (maximum infarct volume) to 14 days (minimum infarct volume) post-MCAO. In addition, SHP-1 protein levels are upregulated following cerebral ischemia and this increase peaks at 7 days post-MCAO. Analysis of confocal images further reveals that immunoreactivity for SHP-1 occurs predominantly in GFAP+ reactive astrocytes, although a small percentage of F4-80+ microglia are also double labeled for SHP-1 at early times post-MCAO. These SHP-1+ reactive astrocytes do not appear to enter the cell cycle (as defined by PCNA immunoreactivity), confirming our previous studies in the avian auditory brainstem. These results suggest that SHP-1 plays an important role in the regulation of glial activation and proliferation in the ischemic CNS.     

Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells

Oral administration of CDP-choline to rats raises plasma and brain cytidine levels and increases brain levels of phosphatidylcholine (PC). In contrast, in humans oral CDP-choline increases plasma levels of uridine. To determine whether uridine can also enhance PC synthesis, we developed an assay for CDP-choline, an immediate and rate-limiting precursor in PC synthesis, and measured this intermediate in clonal PC12 rat pheochromocytoma cells incubated with various concentrations of uridine or cytidine. Addition of uridine (50-100 microM) to the incubation medium caused significant elevations in UTP, CT, USAP and CDP-choline levels in PC12 cells. Uridine had no effect on the synthesis of diacylglycerol (DAG) or the activity of the phosphotransferase which catalyzes the synthesis of PC from DAG and CDP-choline. Hence uridine treatment was unlikely to inhibit the conversion of endogenous CDP-choline to PC. These results suggest the possibility that uridine may also enhance PC synthesis in intact brain.     

Assessment of irritant skin reactions using electrical impedance--a comparison between 2 laboratories

To assess interlaboratory variability in the measurement of skin electrical impedance (IMP), we evaluated irritant reactions to sodium lauryl sulfate (SLS) (2%) and nonanoic acid (NAA) (40%) in 2 laboratories. We studied the patch test responses in 40 healthy male and female volunteers between 20 and 30 years of age (20 in each laboratory) with an instrument for measuring IMP. 2 other bioengineering methods and visual scoring were also used to facilitate further illumination of any findings. A strict protocol including all details of the measurement procedure was carefully implemented in both laboratories. The skin reactions were evaluated at 23 h and at 3, 7 and 14 days after exposure. Our findings show that both irritants caused distinct dynamic responses detectable with the bioengineering techniques. Interestingly, the IMP baseline values varied between the 2 laboratories. Moreover, at early stages in the development of irritation (day 1), the irritants induced changes in IMP indices in the opposite direction, which accords with the concept of various IMP patterns of contact dermatitis caused by different irritants. Although the absolute values of IMP differed in both laboratories, the dynamic response patterns were the same.     

Inhibition of IGF-I-induced Erk 1 and 2 activation and mitogenesis in mesangial cells by bradykinin

BACKGROUND: The beneficial effects of therapeutic angiotensin-converting enzyme (ACE) inhibitor treatment against the worsening of glomerulosclerosis during the course of diabetic nephropathy have been widely documented. ACE inhibitors inhibit both angiotensin II formation and bradykinin (BK) degradation, thereby reducing angiotensin II type 1 (AT1) receptor activity and favoring B2-kinin receptor (B2 receptor) activation. Since the involvement of growth factors such as insulin-like growth factor (IGF-I) has been implicated in the early steps of diabetic nephropathy, we investigated the effect of BK on Erk 1 and 2 activation and cell proliferation by IGF-I. METHODS: The activation of Erk 1 and 2 in mesangial cells (MCs) and isolated glomeruli (IG) was investigated by immunoprecipitation and Western blotting during activation of the IGF-I receptor in the presence or absence of BK and of protein kinase C (PKC), tyrosine-kinase and phosphatase selective inhibitors. Mesangial cell proliferation was assessed in vitro by cell counting. RESULTS: In untreated MCs and IG, when added separately, BK and IGF-I both activated Erk 1 and 2. In contrast, in MCs and IG pretreated with BK, the IGF-I-induced Erk 1 and 2 activation was dose-dependently reduced. The inhibitory effect of BK on IGF-I-induced activation of Erk 1 and 2 was completely abolished by addition of a B2 antagonist, by chelation of intracellular calcium and by tyrosine phosphatase inhibition. Additionally, BK reduced MC proliferation induced by IGF-I. CONCLUSIONS: A new inhibitory pathway of the early steps of IGF-I signaling by the B2 receptor is found both in cultured MCs and in IG, which involves a calcium-dependent tyrosine phosphatase activity. Recruitment of this mechanism may account for the beneficial effects of ACE inhibitor treatment on glomerulosclerosis associated with diabetic nephropathies.     

Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Women's Health Study

BACKGROUND: Endometriosis, the presence of endometrial tissue outside the uterus, has an estimated prevalence between 4% and 10%. A recent study reported that women with a hospital discharge diagnosis of endometriosis were at increased risk of cancer at any site, breast cancer, ovarian cancer, and hematopoietic malignancies, especially non-Hodgkin lymphoma (NHL). METHODS: The authors examined whether self-reported diagnosis of endometriosis was associated with increased risk of various cancers in the Iowa Women's Health Study. Incident cancer cases were identified from 1986 through 1998. Cox proportional hazards regression models were used to calculate relative risks and 95% confidence intervals for the particular cancers of interest. RESULTS: Of 37,434 participants in this analysis, 3.8% reported a history of endometriosis at baseline in 1986. After 13 years of follow-up, 1795 breast, 188 ovarian, and 243 NHL cases were detected in the cohort. Endometriosis was not associated with risk of all cancers combined (age-adjusted relative risk [RR], 0.9; 95% confidence interval [CI], 0.7-1.2), breast carcinoma (RR, 1.0; 95% CI, 0.8-1.3), or ovarian carcinoma (RR, 0.8; 95% CI, 0.2-2.4). However, endometriosis was significantly associated with risk of NHL (age-adjusted RR, 1.8; 95% CI, 1.0-3.0), especially diffuse NHL (RR, 3.2; 95% CI, 1.8-5.6). Multivariate adjustment had minimal effect on the point estimates of risk (NHL RR, 1.7; 95% CI, 0.97-2.7; diffuse NHL RR, 3.3; 95% CI, 1.9-5.9). Endometriosis was not associated with elevated risk of lung, urinary tract, endometrial, melanoma, or colorectal carcinomas (RRs, 1.2, 0.8, 1.2, 0.7, and 0.7, respectively). CONCLUSIONS: These results corroborate a previously reported association between endometriosis and increased risk of NHL but not cancer at other sites.     

No association between 25-hydroxyvitamin D and mammographic density.

There is increasing evidence that vitamin D may protect against breast cancer. Some studies have suggested that dietary and supplemental vitamin D is associated with reduced mammographic density, which is highly associated with breast cancer risk, although this evidence is not entirely consistent. We investigated a possible association between circulating 25-hydroxyvitamin D (25OHD), the best indicator of vitamin D status, and quantitative mammographic density in the Minnesota Breast Cancer Family Study. Mean values of mammographic density (both percent and area densities) and circulating levels of 25OHD were compared across categories of covariates using ANOVA. Models were adjusted for age and body mass index, as well as other covariates, and also stratified by dietary calcium intake, menopause, and season. Serum, mammographic density, and questionnaire data were available from 487 women [133 premenopausal and 354 postmenopausal; mean age, 56.4 years (range, 27-85 years)] without breast cancer, and for 73%, the blood was drawn within 1 year of their mammogram. No evidence was found for an association between 25OHD and either percent density or total dense area. There was also no evidence for any association when the data were stratified by season of sample (winter and summer) or menopause. However, both percent density and dense area were lowest among those in the highest vitamin D quartile with calcium intake above the median. Unlike some previous reports, vitamin D does not seem to be related to mammographic density in this cohort.     

Case-control study of increased mammographic breast density response to hormone replacement therapy.

Previous studies have demonstrated an association between current hormone replacement therapy (HRT) use and increased mammographic breast density. Many of these studies have also shown that only 20-35% of women initiating HRT respond in this manner. This subgroup of HRT responders may be at an increased risk of breast cancer. We performed a case-control study to investigate how women who experience increased density in response to HRT (cases) differ from women who do not experience an increase in density with HRT use (controls) with regard to breast cancer risk factors, type of HRT, weight change, and baseline breast density. Participants were female residents of Olmsted County, Minnesota who received routine screening mammograms at the Mayo Clinic. Cases included 172 women identified between the years 1998 and 1999 by Mayo radiologists as having a HRT response. Controls were women who did not experience an increase in mammographic density with HRT use and were matched to cases on age (+/-3 years), menopausal status, duration of HRT, month of initiation of HRT, and months between baseline and follow-up mammograms. Mammograms were obtained from cases and controls before and during HRT therapy. Breast density was read as a four-category Bi-Rads density grade measure and as a quantitative percentage estimate, using a computer-assisted method. Risk factor information was obtained from both chart review and a mammography database of patient-provided information. There was no association between HRT response and first-degree family history of breast cancer [odds ratio (OR), 0.8; 95% confidence interval (CI), 0.4-1.5], parity (OR, 0.8; 95% CI, 0.4-1.7), later age at first birth (OR, 0.8 for age >25 years versus nulliparous women; 95% CI, 0.4-1.8), or history of biopsy (OR, 0.9; 95% CI, 0.6-1.5). There was also no association with baseline weight or change in weight between a woman's baseline and follow-up mammograms. However, there was evidence of an association between HRT response and type of HRT used; women who experienced a mammographic increase in density with HRT had 2.3 greater odds (95% CI, 1.4-3.7) of having taken estrogen-progestin combined therapy than estrogen alone, compared with controls. This association was stronger among women with a baseline weight below the median (OR, 5.2; 95% CI, 1.6-17.6). Also, there was an inverse association between HRT response and baseline density. Because all risk factors examined accounted for only 26% of the variation in the HRT response, genes or other unmeasured factors are thought to be involved.