Initial expression of interferon alpha receptor 2 (IFNAR2) on CD34-positive cells and its down-regulation correlate with clinical response to interferon therapy in chronic myelogenous leukemia

In order to investigate the mechanism of interferon-alpha (IFNalpha) action in the treatment of chronic myelogenous leukemia (CML), we examined surface expressions of both type I interferon receptor 1 (IFNAR1) and 2 (IFNAR2) subunits on CD34-positive cells in bone marrow (BM) in a total of 57 CML patients. Initial cell-surface IFNAR2 expression at diagnosis assessed by flow cytometry widely distributed but showed overall significantly higher expression in CML patients when compared with normal controls. In 15 fresh patients who subsequently received IFNalpha therapy, IFNAR2 expression at diagnosis was significantly higher in cytogenetic good responders than in poor responders. Down-regulation of IFNAR2 expression during IFNalpha therapy was observed only in good responders but not in poor responders. In addition to protein level, both initial high IFNAR2c mRNA expression level and its down-regulation during IFNalpha therapy, in purified CD34-positive cells, were also observed only in good responders. In contrast to IFNAR2, cell-surface IFNAR1 expression was generally lower than IFNAR2, and correlation between either the pretreatment level or down-regulation of IFNAR1 and clinical response was not evident. With in vitro IFNalpha stimulation, CD34-positive cells showed down-regulations of cell-surface IFNAR2, and IFNAR1 to a lesser extent, in one good-responder patient, but not in one poor-responder patient. Serum soluble interferon receptor (sIFNR) was higher in untreated CML patients than in normal controls, without any correlation with clinical response to IFNalpha. Thus, the pretreatment protein and mRNA expression levels of IFNAR2 and their down-regulations during IFNalpha therapy correlate well with IFNalpha response in CML patients.     

Abrogation of potassium bromate-induced renal oxidative stress and subsequent cell proliferation response by soy isoflavones in Wistar rats

Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this study, we show the modulatory effect of soy isoflavones on KBrO3-mediated renal oxidative stress and subsequent cell proliferation response in Wistar rats. KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, activities of renal anti-oxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase with enhancement in xanthine oxidase, lipid peroxidation, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2). KBrO3 treatment also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.05), lipid peroxidation, gamma-glutamyl transpeptidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). There was also significant recovery of renal glutathione content (P < 0.01), anti-oxidant enzymes and phase-II metabolising enzymes (P < 0.001). Thus, our results show that soy isoflavones acts as potent chemopreventive agent against KBrO3-mediated renal oxidative stress, toxicity and subsequent cell proliferation response in Wistar rats.     

Granulocyte colony-stimulating factor receptors on CD34++ cells in patients with myelodysplastic syndrome (MDS) and MDS-acute myeloid leukemia

We studied surface expression of granulocyte colony-stimulating factor receptor (G-CSFR) on CD34⁺⁺ progenitor cells of myelodysplastic patients. Late stages of disease showed a higher proportion of high or low G-CSFR expression than early stages. Most of the patients with the low expression had neutropenia. Neutropenia was relatively less present in the normal group, but it reappeared in the high group. All the neutropenic patients in the high group showed response to G-CSF, while response in the normal group was minor. These findings suggest that lowered expression of G-CSFR leads to neutropenia in myelodysplastic patients. This article reviewed the knowledge of the G-CSFR and its role in the disorders of granulopoiesis, including myelodysplastic syndrome (MDS).     

The peri-albumen layer: a novel structure in the envelopes of an avian egg

The present paper describes a novel structure, termed the peri-albumen layer, in the egg-envelopes of the quail Coturnix japonica. It reacts with Alcian blue and exists between the egg white and the shell membrane. Ultrastructurally, it is of fine granular structure and forms a fenestrate sheet, the width of which is 190 nm or less. Isolated materials of the peri-albumen layer include an Alcian-blue-positive polysaccharide of 260 kDa, and three glycoproteins of 160, 108 and 52 kDa. The layer is supplied to an egg when it passes through the magnum-isthmus junction, the normalized length of which is 0.62-0.63 of the oviduct. The mucosa of the junction consists exclusively of a luminal epithelium. It is apparently distinct from the mucosa of the magnum and the isthmus, which consist of a luminal epithelium and tubular glands. The luminal epithelium of the magnum-isthmus junction stains prominently with Alcian blue and consists of alternately distributed ciliated cells and granular cells. Immunohistochemistry with an antiserum raised against the materials of the peri-albumen layer revealed the staining of the peri-albumen layer of the egg, and secretory cells of the luminal epithelium at the magnum-isthmus junction. It was concluded that the materials of the peri-albumen layer are produced by secretory cells at the magnum-isthmus junction of the oviduct.     

Morphological correlations between endometrial hyperplasias, uterine leiomyoma and ovarian associated lesions

Morphological evaluation and correlation of endometrial hyperplasias, leiomyoma and ovarian estrogen producing lesions. 390 specimens of hysterectomy associated or not with ovarectomy were processed by routine technique and sections stained by H&E staining. 316 cases presented different degrees of endometrial hyperplasias associated with leiomyoma. In 117 from 170 cases the ovary presented estrogen secreting lesions (follicular cyst, polycystic ovary, stromal hyperplasia, granulosa cell tumours). The highest frequency of the uterine and ovarian lesions was in the decades 41-50 years, and 31-40 years. Leiomyoma and endometrial hyperplasia, develop in a hormonal context, most frequently characterized by micropolicystic ovaries. The risk is higher in the perimenopausal period. The most frequent type is simple hyperplasia suggesting a rare progression to highest grades and a possible protective role of leiomyoma as target tissue which capture estrogens.     

Value of steroid receptors assessment in atypical endometrial hyperplasia

To evaluate if the immunohistochemical assessment of steroid receptors is helpful in distinguishing Atypical Hyperplasia from Well Differentiated Endometrial Carcinoma, the morphological and immunohistochemical features for steroid receptors were studied in 46 cases of atypical hyperplasia alone or associated with other degrees of hyperplasia or adenocarcinoma. The estrogen and progesterone receptors were determined by the avidin-biotin complex technique using monoclonal antibodies on paraffin embedded tissue. The diagnosis of atypical hyperplasia was based on the observation of epithelial atypias and the absence of the stromal invasion. The positive reaction for steroid receptors was moderate, very variable from case to case, heterogeneous and quite similar to that observed in carcinoma. The morphological identification of the stromal invasion is the most reliable criterion in differentiating endometrial carcinoma from atypical hyperplasia. The steroid receptors assessment is not valuable in this purpose but may be useful in cases in which a hormonal therapy is recommended.     

Medical and social implication of cervical cancer screening

Invasive cervical cancer represents a major health problem in Romania. When there is a functioning screening network, the incidence of invasive lesions has a marked reduction, this program being the most successful cancer prevention program of all times. 80% of the actual incidence and mortality from this disease occurs in countries without an organized screening. A good infrastructure of the cytopathologist--practitioner relation must be achieved in order to reach the standard of early detection of the preinvasive cervical lesions.     

Modulation of biochemical parameters by Hemidesmus indicus in cumene hydroperoxide-induced murine skin: possible role in protection against free radicals-induced cutaneous oxidative stress and tumor promotion

Hemidesmus indicus has been shown to possess significant activity against immunotoxicity and other pharmacological and physiological disorders. In this communication, we have shown the modulating effect of H. indicus on cumene hydroperoxide-mediated cutaneous oxidative stress and tumor promotion response in murine skin. Cumene hydroperoxide treatment (30 mg per animal) increased cutaneous microsomal lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes and depletion in the level of glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes was observed. Cumene hydroperoxide treatment also induced the ornithine decarboxylase activity and enhanced the [3H]-thymidine uptake in DNA synthesis in murine skin. Application of ethanolic extract of H. indicus at a dose level of 1.5 and 3.0mg/kg body weight in acetone prior to that of cumene hydroperoxide treatment resulted in significant inhibition of cumene hydroperoxide-induced cutaneous oxidative stress, epidermal ornithine decarboxylase activity and enhanced DNA synthesis in a dose-dependent manner. Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation and xanthine oxidase activity were significantly reduced (P<0.01). In addition the depleted level of glutathione, inhibited activities of antioxidants and phase II metabolizing enzymes were recovered to significant level (P<0.05). In summary, our data suggest that H. indicus is an effective chemopreventive agent in skin and capable of ameliorating hydroperoxide-induced cutaneous oxidative stress and tumor promotion.     

Operative management of rigid congenital club feet in Bangladesh

We report the early results of the surgical treatment of 59 rigid congenital clubfeet in 42 patients. All the feet were operated on in the same hospital by using a one-stage posteromedial release in 41 patients. The patients were divided into two groups as 24 patients (32 feet) had come to the hospital from rural areas, whereas 18 patients (28 feet) all came from the local semi-urban area. After an average of 2 years and 3 months 44 feet were graded either excellent or good, 7 were fair, and 8 had not been adequately corrected. The best results were seen in children who were operated on between the ages of 1 and 3 years. Those from the semi-urban area and who received adequate long-term postoperative care were slightly better.