Congenital nephrotic syndrome-a treatable cause

A 27-day-old infant from a tribal area presented with congenital nephrotic syndrome (CNS). The presence of clinical features of syphilis, proven syphilis in the mother and complete recovery following penicillin therapy confirmed a diagnosis of congenital syphilis. In developing countries, treatable causes of CNS such as syphilis need to be considered in infants presenting with nephrotic syndrome.     

Lymph node biopsy results for desmoplastic malignant melanoma

Desmoplastic malignant melanoma (DMM) is a rare variant of melanoma with distinct histopathologic and clinical features. Compared with other melanomas, the desmoplastic variant demonstrates a greater frequency of local recurrence and a proclivity for tracking along nerves, but it poses a lower risk of distant metastases. Elective lymph node dissection and sentinel lymph node biopsy (SLNB) are commonly used tools for determining prognosis in thick melanomas. The role of these procedures for DMM remains unclear. This study was designed to characterize DMM and determine the frequency of histologically positive lymph nodes in patients with DMM. This retrospective chart review included patients with DMM treated by Johns Hopkins Hospital (JHH) physicians between 1998 and 2003. Among the 28 patients included in the study, 18 patients had biopsies performed on lymph nodes (15 SLNBs and 3 radical neck dissections). One patient had a sentinel lymph node with histology positive for DMM. All others had negative results from histology and S100 stains. This study suggests that the frequency of positive SLNBs in DMM may be substantially lower than that of other melanomas.     

Stimulated growth of human and pig epidermal nerve fibers by tape stripping

Nerve growth studies in adults usually rely upon nerve regeneration that follows axon disruption. In this study elongation of the epidermal nerve fibers occurred in human and pig epidermis stimulated to hypertrophy by removing the stratum corneum with repetitive applications of tape (tape stripping). Epidermal thickening was accompanied by elongation of the epidermal nerve fibers. This study demonstrates that changing the cellular and chemical environment of nerves by tape stripping is a feasible method to study nerve fiber growth in a physiological manner.     

Genetic and epigenetic changes in rat preneoplastic liver tissue induced by 2-acetylaminofluorene

Genotoxic carcinogens, including 2-acetylaminofluorene (2-AAF), in addition to exerting their genotoxic effects, often cause a variety of non-genotoxic alterations in cells. It is believed that these non-genotoxic effects may be indispensable events in tumorigenesis; however, there is insufficient knowledge to clarify the role of carcinogens in both the genetic and epigenetic changes in premalignant tissues and a lack of conclusive information on the link between epigenetic alterations and carcinogenic exposure. In the current study, we investigated whether or not the mechanism of 2-AAF-induced hepatocarcinogenesis consists of both genotoxic (genetic) and non-genotoxic (epigenetic) alterations. Male and female Sprague-Dawley rats were fed NIH-31 diet containing 0.02% of 2-AAF for 6, 12, 18 or 24 weeks. The levels of DNA adducts obtained from 2-AAF in liver and kidney tissues were assessed by high-performance liquid chromatography combined with electrospray tandem mass spectrometry (HPLC-ES-MS/MS). N-(Deoxyguanosine-8-yl)-2-aminofluorene was the major adduct detected at all time points in both tissues. Global DNA methylation in the livers and kidneys, as determined by an HpaII-based cytosine extension assay and by HPLC-ES-MS/MS, did not change over the 24-week period. In the livers of male rats, there was a progressive decrease of global and long interspersed nucleotide element-1-associated histone H4 lysine 20 trimethylation, as well as hypermethylation of the p16(INK4A) gene. These epigenetic changes were not observed in the livers of female rats or the kidneys of both sexes. Importantly, morphological evidence of formation and progression of neoplastic process was observed in the liver of male rats only. In conclusion, we have demonstrated that exposure of rats to genotoxic hepatocarcinogen 2-AAF, in addition to formation of 2-AAF-specific DNA lesions, resulted in substantial alterations in cellular epigenetic status.     

Tumorigenicity and genotoxicity of an environmental pollutant 2,7-dinitrofluorene after systemic administration at a low dose level to female rats

Environmental pollution with nitroaromatic compounds may pose health hazards. We have examined the tumorigenicity in female Sprague-Dawley rats of 2,7-dinitrofluorene (2,7-diNF) and 9-oxo-2,7-diNF administered by intraperitoneal (i.p.) and oral routes at 10 micromol/kg body weight, 3 times per week for 4 weeks. After i.p. treatment, the estimated median latency for the combined malignant and benign mammary tumors was decreased in 2,7-diNF- (p = 0.003) or 9-oxo-2,7-diNF-treated (p = 0.007), relative to vehicle-treated rats (42 or 64 vs. 80 weeks, respectively), whereas after oral dosing, there were no significant differences. At 90 weeks, the malignant mammary tumor incidence in 2,7-diNF-, 9-oxo-2,7-diNF- and vehicle-i.p. treated rats was 44 (p = 0.02 vs. vehicle-treated), 25 and 6%, respectively. Liver and mammary gland DNA was analyzed by HPLC combined with electrospray tandem mass spectrometry for the presence of a deoxyguanosine (dG-2,7-diNF) adduct and a deoxyadenosine (dA-2,7-diNF) adduct derived from 2,7-diNF, and a deoxyguanosine (dG-9-oxo-2,7-diNF) adduct derived from 9-oxo-2,7-diNF. Both dG-2,7-diNF and dA-2,7-diNF were detected in DNA of 2,7-diNF-treated rats, whereas only very low levels of dG-9-oxo-2,7-diNF were detected in DNA of 9-oxo-2,7-diNF-treated rats. After i.p. treatment, the dA-2,7-diNF level was higher (p < 0.01) in the mammary gland than liver (13.6 vs. 7.8 adducts/10(8) nucleotides). In the mammary gland, the dG-2,7-diNF level was higher (p < 0.05) after i.p. than oral dosing and also higher (p < 0.05) than in the liver (36 vs. 8.6 and vs. 9.1 adducts/10(8) nucleotides, respectively). The preferential display of carcinogenicity and genotoxicity in the mammary gland by low doses of 2,7-diNF signifies its potential relevance for environmental breast cancer.     

Ten years of battle with multiple recurrences of pediatric skull base chondrosarcoma: A case report

In children and adolescents presenting with skull base sarcoma, treatment strategies will face challenging decisions due to the unique chemoresistant pathologies, limitations imposed by the not‐yet fully mature anatomical structures, and the small surgical site.     

The association of HLA class II DR B1 alleles with HCV infection in Egyptian children

Background and study aimsHuman leucocyte antigens (HLA) class II appear to play an important role in the individual’s immune response to viral infection. The aim of this study is to assess the relationship between HLA class II antigens with the clinical, laboratory and histopathological state of the liver in Egyptian children and adolescents with chronic hepatitis C virus (HCV) infection.Patients and methodsThe study included 46 chronically infected HCV children and adolescents without – hepatitis B virus (HBV) nor human immunodeficiency virus – (HIV). Their mean age was 10.4 ± 4.23 years (3–17). HLA-DRB typing was done by polymerase chain reaction (PCR) for the patients and 20 control subjects. Biochemical and haematological parameters were assessed as well as a liver biopsy was taken from the included patients.ResultsThe most frequent alleles demonstrated among patients were DRB1103, DRB1104 and DRB1113 (45.6%, 39.1% and 26.1%), respectively. Analysis of DRB1 frequencies between patients and control revealed that DRB1*15 is significantly reduced among patients when compared with the control group (p < 0.01). Patients possessing the allele DRB1*03 had significantly reduced platelet count (p = 0.03), and this allele was presented to a greater extent in patients with minimal grade of inflammation. Patients with DRB1*04 had significantly low serum albumin (p = 0.04) and patients with DRB1*13 had significantly high serum aspartate aminotransferase (AST) levels (p = 0.05).ConclusionIn Egyptian HCV-infected children, special HLA patterns were found; HLA DRB1*03 was present in nearly half of the patients, while the frequency of HLA DRB1*15 was significantly reduced among the cases in comparison to the control subjects.     

Effect of human umbilical cord blood CD34+ progenitor cells transplantation in diabetic mice

Shortage of donor organs spurs research into alternative means of generating β cells. Stem cells might represent a potential source of tissues for cell therapy protocols, and diabetes is a candidate disease that may benefit from cell replacement protocols. We examined the effect of transplanted human umbilical cord blood CD34+ cells on some detailed parameters in streptozotocin- (STZ) induced diabetic mice. An experimental study was conducted in the departments of clinical pathology, physiology and pathology of Faculty of Medicine, Suez Canal University. Thirty male albino mice 8–12 weeks were included and subdivided into 3 groups, first group served as normal control group, second group as diabetic control after induction of diabetes with STZ and third group treated diabetic mice by injection of positively selected CD34 progenitor cells from human umbilical cord blood (HUCB) with a dose of one million cells/mouse. Blood glucose and serum insulin were measured at specific time interval and immunohistochemical (IHC) analysis and histopathology on pancreas were conduced. Data were analyzed using chi square between groups. Intravenous injection of CD34+ cells caused significant improvement in blood glucose level (277.9?±?102.5 mg/dl in treated group vs 530.3?±?99 mg/dl in untreated group, p?<?0.01). Blood level of mouse insulin was higher in the treated group as compared with untreated diabetic mice (0.77?±?0.2 ng/ml in treated group versus 0.26?±?0.09 in untreated group, p?<?0.001). IHC analysis for detection of human insulin producing cells in pancreas of treated mice revealed that 33.3% positive cellular staining and 55.6% positive sinusoidal staining were detected. In conclusion, Transplantation of HUCB-CD34+ cells appear to be a modality of stem cell therapy in diabetes mellitus.