The pp60c-src in retinal pigment epithelium and its modulation by vasoactive intestinal peptide.

The pp60c-src is present at high level in differentiated retinal pigment epithelium (RPE) in culture. Immunofluorescence microscopy using GD11 (anti-pp60c-src) shows intense staining in the plasma membrane, especially at the cell-cell junctions, and diffuse staining in the cytoplasma. Western blot analysis shows that the majority of the GD11-reactive molecules is localized in the membrane. The pp60c-src does not translocate between membrane and cytoplasma when the RPE was reacted with vasoactive intestinal peptide (VIP), which is previously shown to stimulate phosphorylation of the pp60c-src in the membranes (Biochem. Biophys. Res. Commun. 174, 452-8, 1991). Here, VIP modulation is shown to alter the reactivity of pp60c-src with a monoclonal anti-phosphotyrosine antibody.     

School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study

BackgroundConflicting results have been reported concerning possible adverse effects on the cognitive function of offspring of mothers with type 1 diabetes (O-mT1D). Previous studies have included offspring of parents from the background population (O-BP), but not offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group.Methods and findingsThis is a population-based retrospective cohort study from 2010 to 2016. Nationally standardized school test scores (range, 1 to 100) were obtained for public school grades 2, 3, 4, 6, and 8 in O-mT1D and compared with those in O-fT1D and O-BP. Of the 622,073 included children, 2,144 were O-mT1D, and 3,474 were O-fT1D. Multiple linear regression models were used to compare outcomes, including the covariates offspring with type 1 diabetes, parity, number of siblings, offspring sex, smoking during pregnancy, parental age, and socioeconomic factors. Mean test scores were 54.2 (standard deviation, SD 24.8) in O-mT1D, 54.4 (SD 24.8) in O-fT1D, and 56.4 (SD 24.7) in O-BP. In adjusted analyses, the mean differences in test scores were −1.59 (95% CI −2.48 to −0.71, p < 0.001) between O-mT1D and O-BP and −0.78 (95% CI −1.48 to −0.08, p = 0.03) between O-fT1D and O-BP. No significant difference in the adjusted mean test scores was found between O-mT1D and O-fT1D (p = 0.16). The study’s limitation was no access to measures of glycemic control during pregnancy.ConclusionsO-mT1D achieved lower test scores than O-BP but similar test scores compared with O-fT1D. Glycemic control during pregnancy is essential to prevent various adverse pregnancy outcomes in women with type 1 diabetes. However, the present study reduces previous concerns regarding adverse effects of in utero hyperglycemia on offspring cognitive function.

Anne Lærke Spangmose and colleagues examine the association between school performance and exposure to maternal or paternal type 1 diabetes in utero in Denmark.     

Severely reduced production of klotho in human chronic renal failure kidney

We recently identified a novel gene, termed klotho (kl) that is involved in the development of a syndrome in mice resembling human aging. A defect of the kl gene expression in mice leads to multiple disorders including arteriosclerosis, osteoporosis, ectopic calcification, and skin atrophy together with short life-span and infertility. Patients with chronic renal failure (CRF), develop multiple complications that are reminiscent of phenotypes observed in kl mutant mice. Furthermore, the kl gene is mainly expressed in kidney and brain. These evidences above suggest the possible involvement of Klotho function in the complications arising in CRF patients. To investigate the above possibility, we examined the kidneys of 10 clinically or histologically diagnosed CRF cases. The level of kl gene expression was measured by utilizing RNase protection assay. The expression of Klotho protein was assayed by utilizing Western blot analysis and by immunohistochemistry. The levels of kl mRNA expression were greatly reduced in all CRF kidneys. Moreover, the production of Klotho protein was also severely reduced in all CRF kidneys. These results suggest that the decrease in kl gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients.     

Chondrosarcoma of the proximal femur with myxoid degeneration mistaken for chondromyxoid fibroma in a young adult. A case report

BACKGROUND: Fine needle aspiration cytology (FNAC) is effective in the diagnosis of bone tumors when combined with careful radiologic and clinical evaluation. However, cases where clinical or radiologic findings are atypical or unusual may lead to an erroneous diagnosis. CASE: A 19-year-old male presented with a pain in the left hip area that had been slowly progressive over a 10-month period. Clinical and radiologic findings suggested either giant cell tumor or chondroblastoma. The smeared aspiration specimen showed loosely cohesive, oval to round cells with moderate amounts of pale pink cytoplasm admixed with pinkish-blue, chondromyxoid material. The individual cells contained a single nucleus with evenly distributed, fine chromatin. A few osteoclastic giant cells were scattered in the smears. A cytologic diagnosis of myxoid lesion with a few giant cells, suspicious for chondromyxoid fibroma, was made. The diagnosis of chondrosarcoma was made by subsequent histologic examination. CONCLUSION: Absence of the usual clinicoradiologic features of chondrosarcoma combined with an unusual cytologic presentation in this case led to a misdiagnosis. In most centers, FNAC has achieved undisputed status as a diagnostic tool, and cytologic diagnosis often forms the basis of the therapeutic protocol. However, at some sites FNAC diagnosis is more problematic. Awareness of the limitations and pitfalls of FNAC is just as important as knowledge of the scope of FNAC in bone tumors. Tumors with chondromyxoid features provide particular difficulties.