Pure red cell aplasia: Clinical features and treatment results in 16 cases

 Pure red cell aplasia (PRCA) is a rare hematological disease characterized by selective marrow erythroid aplasia. We report the clinical features and treatment results of 16 Chinese patients with PRCA. Nine (56%) cases were not associated with any underlying disorders and were considered idiopathic, while seven patients (44%) had associated diseases, three involving the thymus, two with T large granular lymphocyte leukemia (T-LGLL), and one each with Stevens-Johnson syndrome and acute hepatitis A. Conventional-dose corticosteroid therapy resulted in complete remission in three of 13 patients. Cyclosporin A was used in six patients. There were three complete and one partial remissions. High-dose methylprednisolone was ineffective in four patients who failed conventional-dose corticosteroids but achieved complete remission in one patient with thymoma who did not respond to thymectomy. Antithymocyte globulin was used in four patients, resulting in partial remission in only one patient with concomitant T-LGLL. Intravenous gamma globulin and danazol were ineffective in three patients. Thymectomy was performed in two patients, with one patient remitting. This is the largest series of PRCA reported in an oriental population. Our results indicate that treatment of PRCA may still be problematic and better therapeutic strategy will have to be defined. Received: 11 September 1995 / Accepted: 1 January 1996     

Age and prior caffeine use alter the cardiovascular and adrenomedullary responses to oral caffeine

The effects of age and chronic caffeine use (approximately 300 mg/day) on the cardiovascular and humoral responses to 250 mg of oral caffeine (the equivalent of 2 to 3 cups of coffee) were examined. Older subjects had greater increases in blood pressure than younger subjects (p less than 0.03), and caffeine nonusers had greater blood pressure increases than caffeine users, regardless of age (p less than 0.05). Caffeine increased the product of systolic blood pressure and heart rate (an estimate of myocardial oxygen demand) in older caffeine nonusers, but this effect was absent in older caffeine users (p less than 0.01). Cardiovascular effects of caffeine could not be related temporally to changes in plasma epinephrine, which were greater in caffeine nonusers and younger subjects, or to plasma norepinephrine, renin activity or vasopressin, which did not change. Thus, age accentuates and moderate prior caffeine use attenuates the cardiovascular effects of oral caffeine; these effects are not mediated solely through the sympathoadrenal system.     

KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low‐grade serous carcinoma

BRAF and KRAS mutations in ovarian serous borderline tumours (OSBTs) and ovarian low‐grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or whether those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumour samples from 23 recurrent LGSC patients with a known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for five patients, and either OSBTs or LGSCs were available for another 18 patients. Tumour cells from paraffin‐embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumours that appeared to have wild‐type KRAS by conventional PCR–Sanger sequencing were further analysed by full COLD (co‐amplification at lower denaturation temperature)‐PCR and deep sequencing. Full COLD‐PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR–Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in ten patients. Full COLD‐PCR deep sequencing detected low‐abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in seven OSBT samples and six LGSC samples. Surprisingly, patients with the KRAS G12V mutation have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumour cells with or without detectable KRAS mutations. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Is multiple SNP testing in BRCA2 and BRCA1 female carriers ready for use in clinical practice? Results from a large Genetic Centre in the UK

BRCA1 and BRCA2 are major breast cancer susceptibility genes. Nineteen single nucleotide polymorphisms (SNPs) at 18 loci have been associated with breast cancer. We aimed to determine whether these predict breast cancer incidence in women with BRCA1/BRCA2 mutations. BRCA1/2 mutation carriers identified through the Manchester genetics centre between 1996 and 2011 were included. Using published odds ratios (OR) and risk allele frequencies, we calculated an overall breast cancer risk SNP score (OBRS) for each woman. The relationship between OBRS and age at breast cancer onset was investigated using the Cox proportional hazards model, and predictive ability assessed using Harrell's C concordance statistic. In BRCA1 mutation carriers we found no association between OBRS and age at breast cancer onset: OR for the lowest risk quintile compared to the highest was 1.20 (95% CI 0.82–1.75, Harrell's C = 0.54), but in BRCA2 mutation carriers the association was significant (OR for the lowest risk quintile relative to the highest was 0.47 (95% CI 0.33–0.69, Harrell's C = 0.59). The 18 validated breast cancer SNPs differentiate breast cancer risks between women with BRCA2 mutations, but not BRCA1. It may now be appropriate to use these SNPs to help women with BRCA2 mutations make maximally informed decisions about management options.     

Comparative genomic hybridization: comparison between esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-incidence area for both cancers in Henan, northern China

Esophageal squamous cell carcinoma (SCC) remains the leading cause of cancer related deaths in Linzhou (formerly Linxian), the highest incidence area for esophageal cancer (EC) in Henan, northern China. In China, gastric cardia adenocarcinoma (GCA) shares very similar geographic distribution with SCC, suggesting the possibility of similar risk factors involved in SCC and GCA carcinogenesis in these areas. However, the underlying genetic alterations for esophageal and gastric cardia carcinogenesis, especially for the molecular difference between SCC and GCA, are largely unknown. The present study was thus undertaken to determine the difference in chromosomal aberrations in SCC (n = 37) and GCA (n = 31) using the comparative genomic hybridization method (CGH). All the patients were from Linzhou, Henan, a high-risk geographic region for both SCC and GCA. CGH results showed that chromosomal aberrations with different degrees were identified both in SCC and GCA. In SCC, chromosomal profile of DNA copy number was characterized by most frequently detected gains at 8q (29/37, 78%), 3q (24/37, 65%) and 5p (19/37, 51%); and frequently detected losses at 3p (21/37, 57%), 8p and 9q (14/37, 38%). In GCA, the frequently detected gains were identified at 20q (13/31, 42%), 6q (12/31, 39%) and 8q (11/31, 35%); the DNA copy number losses in GCA occurred frequently at 17p (17/31, 55%), 19p (15/31, 48%) and 1p (14/31, 45%). Statistically, there were evident differences between SCC and GCA in DNA copy number gains at 8q, 3q, 5p and 20q (P < 0.05) and in losses at 3p, 8p, 5q, 17p and 18q (P < 0.05). Gains at 8q were frequently observed in both SCC and GCA. Gains at 3q and 8p were frequently observed in TNM stage III of both SCC and GCA. The present CGH results provide candidate regions that may contain specific related genes involved in SCC and GCA in the Linzhou population. Gains at 8q, 3q and 5p and losses at 3p, 8p and 9q were specifically implicated in SCC; gains at 20q, 6q and 8q and losses at 17p, 19p and 1p were specifically implicated in GCA; gains at 8q were implicated in both SCC and GCA.     

A long-term follow-up study on hepatitis B surface antigen-positive patients undergoing allogeneic hematopoietic stem cell transplantation

The long-term hepatic complications after allogeneic hematopoietic stem cell transplantation (HSCT) in hepatitis B virus (HBV) endemic area are unknown. We examined the serological and liver-related outcome of 803 consecutive patients who received allogeneic HSCTs, with a median follow-up period of 83 months (range, 0.5-155 months). Late HBV-related hepatitis occurred in 2 of the 721 hepatitis B surface antigen-negative (HBsAg-) recipients compared with 16 of the 82 HBsAg+ recipients after HSCT (0.3% vs 19.5%; P < .001 by log-rank). Liver cirrhosis developed in 8 of the 82 HBsAg+ recipients compared with none of the 721 HBsAg- recipients (9.8% vs 0%; P < .001 by log-rank). Twenty of the 31 (64.5%) HBsAg+ recipients of hematopoietic stem cells from donors with natural immunity to HBV had sustained serologic clearance of HBsAg after HSCT. Eight of the 62 recipients without sustained HBsAg clearance compared with none of the 20 recipients with sustained HBsAg clearance developed liver cirrhosis (12.9% vs 0%; P = .02 by log-rank). Our study showed that long-term hepatic complications occur in a significant proportion of HBsAg+ patients after HSCT and the incidence of liver cirrhosis is reduced in those with sustained serologic clearance of HBsAg after HSCT.     

Endothelial-like nitric oxide synthase immunolocalization by using gold nanoparticles and dyes

Immunofluorescence is a biological technique that allows displaying the localization of the target molecule through a fluorescent microscope. We used a combination of gold nanoparticles and the fluorescein isothiocianate, FITC, as optical contrast agents for laser scanning confocal microscopy imaging to localize the endothelial-like nitric oxide synthase in skeletal muscle cells in a three-dimensional tissue phantom at the depth of 4µm. The FITC detected fluorescence intensity from gold-nanoparticles-labelled cells was brighter than the emission intensity from unlabelled cells.OCIS codes: (170.1790) Confocal microscopy, (280.1415) Biological sensing and sensors